VPH, VIRUS DEL PAPILOMA HUMANO./ HPV, HUMAN PAPILLOMA VIRUS.

 

The HPV in our World,  Before Vaccines. !

 

El VPH en nuestro Mundo, antes de las Vacunas. !

PUBLICADO 2.017 ACTUALIZADO 2.023

EDITORIAL ESPAÑOL 
===================
Hola amigos de la red DERMAGIC EXPRESS hoy te va a poner una publicación sobre el VPH, la cual fue la edición No, 69 de este espacio Web que originalmente como te explique en la HISTORIA del mismo, nació en 1.998. Para aquel entonces, no EXISTIA NINGUNA VACUNA PARA EL VPH, el cual se diseminaba rápidamente por el mundo, y realice una publicación a la cual le puse el nombre de EL VPH Y SU COMPORTAMIENTO EN NUESTRO MUNDO.

Incluí el comportamiento del VPH en 43 países los cuales están allí mencionados y estaba lejos la aparición de las VACUNAS contra el mismo. El virus del VPH se había convertido en una TRAGEDIA, a nivel mundial desde el punto de vista del contagio y muertes por cáncer, y todavía lo es. La proliferación de los subtipos para aquel entonces eran 82. De estos Los más asociados con neoplasias eran los tipos: 6, 11, 16,18, 31 y 33, y entre estos el 16 y 18 los más frecuentes.

Para Hoy 2.023 hay aproximadamente 200 tipos de VPH, de los cuales 51 especies afectan la mucosa genital estando clasificados así:

1.) Mas carcinogénicos los tipos 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, y 82. 

2.) Probable alto riesgo el 26, 53,y 66, y de 

3.) Bajo riesgo cancerígeno: 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 73, 81, y 108.

El 16 y 18 siguen siendo los más comunes representando el 70% de las infecciones. Se reportan un promedio de 27.000 mil casos nuevos anuales de cáncer por VPH en los Estados Unidos y más de 200.000 mil muertes anuales a nivel mundial.

Esto obviamente condujo a los laboratorios a crear VACUNAS para prevenir la enfermedad, además del ya conocido CONDOM, para evitar el contacto de piel con piel, EL GRAN MECANISMO DE CONTAGIO descrito hasta ahora.

Esto te lo estoy poniendo acá, porque en la próxima edición del DERMAGIC EXPRESS, te voy a hablar bien claro sobre LAS VACUNAS EXISTENTES PARA EL VPH hoy día, 2.023 y si han sido efectivas o no, sus efectos secundarios y si valió la pena o no INVENTARLAS.

"...Para aquel entonces la muerte por VPH era CANCER, hoy día, LAS VACUNAS se inventaron para protegerte DE LOS CEPAS MAS CANCERIGENA, pero....en muchos casos OCASIONAN EFECTOS  ADVERSOS SEVEROS"

"En un periodo de 23 años aparecieron unas 120 CEPAS nuevas DE V.P.H, quizá este aumento cabalgante fue lo que llevo a los laboratorios a FABRICAR VACUNAS para esta enfermedad, la experiencia con las mismas ha sido CONTROVERSIAL"

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AQUI TE PONGO LA EDICION ORIGINAL No 69 DEL DERMAGIC EXPRESS 18 DE AGOSTO 1.999
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 Hola amigos de la red, DERMAGIC en su edición 69. El tema el bien conocido y famoso VIRUS DEL PAPILOMA HUMANO (VPH). Días atrás me puse a pensar cómo se comporta este VIRUS en las poblaciones de nuestro MUNDO y cuantos realmente existen, hice una investigación en la red y encontré muchas cosas interesantes, entre ellas:

Los estudios fueron hechos en estos países:

Croacia, Francia, Eslovenia, Ámsterdam, Méjico, Brasil, Londres, Filipinas, Alemania, Suecia, Estados Unidos, China, Japón, Italia, Colombia, Irlanda, Singapur, Canadá, Checoslovaquia, España, Australia, Tailandia, Noruega, Groenlandia, Dinamarca, Hungría, Finlandia, Jamaica, Malasia, Kenya, India, Grecia, Alaska, Turquía, Rusia, Venezuela, Ecuador, Perú, Guatemala, Panamá, Israel, Sur África, Las Antillas Neerlandesas.

1.) PARA JULIO DE 1.999 HAY 82 TIPOS REPORTADOS.
 
2.) LOS MÁS ASOCIADOS CON NEOPLASIAS SON LOS TIPOS: 6, 11, 16,18, 31 Y 33, Y ENTRE ESTOS EL 16 Y 18 SON LOS MÁS FRECUENTES.
 
3.) EXISTEN ESTUDIOS QUE DEMUESTRAN UNA ASOCIACIÓN HLA Y SUSCEPTIBILIDAD A NEOPLASIA CERVICAL INTRAEPITELIAL (NIC) POR VPH.
 
4.) SU DISTRIBUCIÓN ES MUNDIAL.
 
5.) NO RESPETAN RAZAS NI CONDICIONES SOCIALES.
 
6.) LAS NUEVAS TÉCNICAS HAN PERMITIDO DETECTAR LOS TIPOS MÁS EXACTAMENTE
 
7.) A PESAR DE LAS CAMPAÑAS DE EDUCACIÓN SEXUAL, CONTINÚAN DISEMINÁNDOSE EN NUESTRO MUNDO.
 
8.) EN LA POBLACIÓN CHINA LOS TIPOS 52 Y 58 TAMBIÉN ESTÁN ASOCIADOS A NEOPLASIA INTTRAEPITELIAL CERVICAL.
 
9.) SE HAN DETECTADO ONCOPROTEINAS, DENOMINADAS E6 Y E7 QUE LE CONFIEREN AL VPH SU CAPACIDAD DE MALIGNIDAD.
 
10.) SE HA ENCONTRADO VIRUS VPH EN LESIONES MALIGNAS O PRE MALIGNAS TALES COMO: QUERATOSIS ACTÍNICA, EPITELIOMA BASOCELULAR, ESPINOCELULAR, ENFERMEDAD DE BOWEN, QUERATOACANTOMAS, CONDILOMA ACUMINADO, ADENOCARCINOMA DEL ÚTERO, LESIONES PRE MALIGNAS DE LA CAVIDAD ORAL Y OTRAS.

 Saquen ustedes otras conclusiones...

Si lees bien las referencias, la humanidad estaba lejos de LAS VACUNAS para el VPH. Y este se estaba extendiendo en todo el mundo. Llegaron en los años 2.000 y ... lejos de convertirse EN UNA SOLUCION se convirtieron en muchos casos un  RELATIVO PROBLEMA MUNDIAL. .... Porque si bien es cierto que se inventaron VACUNAS CONTRA LAS VARIANTES MAS CANCERIGENAS DEL V.P.H, la vacuna NO TE PROTEGE CONTRA TODAS PORQUE SON MÁS DE 200 CEPAS...aparte e ello los EFECTOS ADVERSOS en algunos PUEDEN SER LETALES..

Saludos a todos!!!

Dr. José Lapenta R.

Dr. José M. Lapenta R.,

 

EDITORIAL ENGLISH
=================
Hello friends of the DERMAGIC EXPRESS network today I'm going to put a publication on the HPV (HUMAN PAPILLOMA VIRUS), which was the edition No, 69 of this web space that originally as explain in the HISTORY of the DERMAGIC, who was born in 1.998. At that time, there was NO VACCINE FOR HPV, which spread rapidly around the world, and made a publication to which I named HPV AND ITS BEHAVIOR IN OUR WORLD. 

I included the behavior of HPV in 43 countries which are mentioned there and was far from the appearance of the VACCINES against it. The HPV virus had become a TRAGEDY, worldwide from the point of view of contagion and deaths from cancer, and still is. The proliferation of the subtypes at that time was 82. Of these, the most associated with neoplasias were the types: 6, 11, 16, 18, 31 and 33, and among these, the 16 and 18 most frequent types. 

For today, 2,017, there are approximately 120 HPV types, of which 51 species affect the genital mucosa and are currently the 

1.) Most carcinogenic types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 , 68, 73, and 82. 

2.) Probable high risk, 26, 53, and 66, and of 

3.) Low carcinogenic risk: 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and 108. 

Types 16 and 18 remain the most common accounting for 70% of infections. An average of 27,000 annual new cases of HPV cancer is reported in the United States and more than 200,000 deaths annually worldwide. 

This obviously led laboratories to create VACCINES to prevent disease, in addition to the already known CONDOM, to avoid skin-to-skin contact, THE GREAT CONTAGIUM MECHANISM described until now.

This is why I am putting here this, because in the next edition of DERMAGIC EXPRESS, I will speak clearly about EXISTING HPV VACCINES today, 2,023 and if they have been effective or not, its side effects and if it was worth it or Not INVENTING THEM. 

"... At that time, death from HPV was CANCER, today, VACCINES were invented to protect you FROM THE MOST CANCERIOUS STRAINS, but...in many cases THEY CAUSE SEVERE ADVERSE EFFECTS"

In a period of 23 years, about 120 new HPV STRAINS appeared, perhaps this dramatic increase was what led laboratories to MANUFACTURE VACCINES for this disease, the experience with them has been CONTROVERSIAL

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HERE I GIVE YOU THE ORIGINAL EDITION No. 69 OF DERMAGIC EXPRESS AUGUST 18, 1.999
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Hello friends of the network, DERMAGIC in its 69th issue. The topic the well-known and famous HUMAN PAPILOMA VIRUS (HPV). Days ago I started to think how this VIRUS behaves in the populations of our WORLD and how many actually exist, I did an investigation in the network and I found many interesting things, among them: 

The studies were done in these countries: 

Croatia, France, Slovenia, Amsterdam, Mexico, Brazil, London, Philippines, Germany, Sweden, USA, China, Japan, Italy, Colombia, Ireland, Singapure, Canada, Czech Republic, Spain, Australia, Thailand, Norway, Greenland, Denmark, Hungria, Finland, Jamaica, Malaysia, Kenya, The India, Greek, Alaska, Turkey, Russia, Venezuela, Ecuador, Peru, Guatemala, Panama, Israel, South Africa, The Netherlands .  

1.) By July of 1.999 there are 82 types reported.

2.) The most associated with neoplasias are the types: 6, 11, 16, 18, 31 and 33, and between these the 16 and 18 are the most frequent.

3.) There are studies that demonstrate an HLA association and susceptibility to cervical intraepithelial neoplasia (NIC) by HPV.

4.) Its distribution is worldwide.

5.) Do not respect Races or social conditions.

6.) The new techniques have made it possible to detect the types more accurately

7.) Despite the sex education campaigns, they continue to spread in our world.

8.) In the Chinese population types 52 and 58 are also associated with cervical intraepithelial neoplasia.

9.) Oncoproteins, called E6 and E7, have been detected that confer on 
HPV its capacity for malignancy.

10.) HPV viruses have been found in malignant or pre-malignant lesions such as: actinic keratoses, cell-basal epithelioma, squamous cell carcinoma, Bowen's disease, keratoacanthomas, condyloma acuminata, adenocarcinoma of the uterus, premalignant lesions of the oral cavity, and others.

Draw other conclusions...

If you read well  the references, humanity was far  from THE VACCINES for the HPV. and the HPV was spreading in all WORLD.  They arrived in the years 2.000 and ....  FAR AWAY FROM BECOMING A SOLUTION became a RELATIVE WORLD PROBLEM. .... Because although it is true that VACCINES were invented AGAINST THE MOST CANCEROUS VARIANTS OF HPV, the vaccine DOES NOT PROTECT YOU AGAINST ALL OF THEM BECAUSE THERE ARE MORE THAN 200 STRAINS...aside from that, the ADVERSE EFFECTS in some CAN BE LETHAL

Greetings to all!!! 

Dr. José Lapenta R.,

Dr. José M. Lapenta R.,

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REFERENCIAS BIBLIOGRAFICAS/ BIBLIOGRAPHICAL REFERENCES
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1.) Detection and typing of human papillomaviruses by polymerase chain reaction in cervical scrapes of Croatian women with abnormal cytology. (CROATIA)
2.) Risk factors for HPV DNA detection in middle-aged women. (FRANCE)
3.) Human papillomavirus 16 and 18 infection of the uterine cervix in women with different grades of cervical intraepithelial neoplasia (CIN). (SLOVENIA)
4.) HPV 16 infection and progression of cervical intra-epithelial
neoplasia: analysis of HLA polymorphism and HPV 16 E6 sequence variants. (AMSTERDAM)
5.) HPV prevalence among Mexican women with neoplastic and normal cervixes. (MEXICO)
6.) Cigarette smoking and high-risk HPV DNA as predisposing factors for high-grade cervical intraepithelial neoplasia (CIN) in young Brazilian women. (BRAZIL)
7.) Prevalence of human papillomavirus infection in premalignant and malignant lesions of the oral cavity in U.K. subjects: a novel method of detection. (LONDON)
8.) Causes of cervical cancer in the Philippines: a case-control study. (PHILLIPINES)
9.) Novel HPV types present in oral papillomatous lesions from patients with HIV infection. (GERMANY)
10.) HPV-types, cytological and histopathological findings in three groups of women with possible HPV-related disease. (SWEDEN)
11.) A general primer GP5+/GP6(+)-mediated PCR-enzyme immunoassay method for rapid detection of 14 high-risk and 6 low-risk human papillomavirus genotypes in cervical scrapings. (AMSTERDAM)
12.) Prevalence of antibodies to human papillomavirus (HPV) type 16 virus-like particles in relation to cervical HPV infection among college women. (USA)
13.) Detection of human papillomavirus mRNA and cervical cancer cells in peripheral blood of cervical cancer patients with metastasis. (TAIWAN)
14.) Human papillomavirus in tissue of bladder and bladder carcinoma specimens. A preliminary study. (GERMANY)
15.) Detection of human papillomavirus (HPV) type 47 DNA in malignant lesions from epidermodysplasia verruciformis by protocols for precise typing of related HPV DNAs. (JAPAN)
16.) HLA and susceptibility to cervical neoplasia. (NETHERLANDS)
17.) Non-isotopic in situ hybridization of HPV types in cervical intraepithelial lesions in patients with AIDS. (BRAZIL)
18.) HLA-A2-restricted peripheral blood cytolytic T lymphocyte response to HPV type 16 proteins E6 and E7 from patients with neoplastic cervical lesions. (GERMANY)
19.) Human papilloma virus 16-18 infection and cervical cancer in Mexico: a case-control study. (MEXICO)
20.) Detection of human papillomavirus (HPV) type 6, 16 and 18 in head and neck squamous cell carcinomas by in situ hybridization. (CROATIA)
21.) Prevalence of human papillomavirus infection in women attending a sexually transmitted disease clinic. (JAPAN)
22.) Demonstration of multiple HPV types in laryngeal premalignant lesions using polymerase chain reaction and immunohistochemistry. (ITALY)
23.) Adenocarcinoma of the uterine cervix in Ireland and Sweden: human papillomavirus infection and biologic alterations. (IRELAND AND SWEDEN)
24.) Risk factors for high-risk type human papillomavirus infection among Mexican-American women. (USA-MEXICO)
25.) Many different papillomaviruses have low transcriptional activity in spite of strong epithelial specific enhancers. (SINGAPORE)
26.) Low frequency of human papillomavirus infection in initial papillary bladder tumors. (CANADA)
27.) Human papillomavirus genotype spectrum in Czech women: correlation of HPV DNA presence with antibodies against HPV-16, 18, and 33 virus-like particles. (CZECH REPUBLIC)
28.) Mucosal oncogenic human papillomaviruses and extragenital Bowen disease. (FRANCE) 29.) High prevalence of a variety of epidermodysplasia verruciformis-associated human papillomaviruses in psoriatic skin of patients treated or not treated with PUVA. (GERMANY)
30.) Human papillomavirus type 31 oncoproteins E6 and E7 are required for the maintenance of episomes during the viral life cycle in normal human keratinocytes. (USA)
31.) Clinical, histopathologic, and molecular aspects of cutaneous human papillomavirus infections. (USA)
32.) Screening for genital human papillomavirus: results from an international validation study on human papillomavirus sampling techniques. (SPAIN)
33.) Use of the same archival papanicolanou smears for detection of human papillomavirus by cytology and polymerase chain reaction. (AUSTRALIA)
34.) Detection and typing of human papillomavirus in cervical cancer in the Thai. (THAILAND)
35.) Correlation between polymerase chain reaction and cervical cytology for detection of human papillomavirus infection in women with and without dysplasia. (NORWAY)
36.) Detection and quantitation of human papillomavirus by using the fluorescent 5' exonuclease assay. (SWEDEN)
37.) Risk factors for HPV detection in archival Pap smears. A population-based study from Greenland and Denmark. (GREENLAND AND DENMARK)
38.) [Human papillomavirus infection in women with and without abnormal cervical cytology]. (MEXICO)
39.) Follow-up of human papillomavirus (HPV) DNA and local anti-HPVantibodies in cytologically normal pregnant women. (HUNGARY)
40.) Relatively low prevalence of human papillomavirus 16, 18 and 33 DNA inthe normal cervices of Japanese women shown by polymerase chain reaction. (JAPAN)
41.) Comparison of a one-step and a two-step polymerase chain reaction with degenerate general primers in a population-based study of human papillomavirus infection in young Swedish women. (SWEDEN)
42.) Human papillomavirus DNA in unselected pregnant and non-pregnant women. (FINLAND)
43.) Prevalence of HPV cervical infection in a family planning clinic determined by polymerase chain reaction and dot blot hybridisation. (LONDON)
44.) Type-specific prevalence of human papillomavirus DNA among Jamaican colposcopy patients. (JAMAICA)
45.) Polymerase chain reaction detection and restriction enzyme typing of human papillomavirus in cervical carcinoma. (MALAYSIA)
46.) Human papillomavirus (HPV) cervical lesions: results from 300 Italian women studied with DNA hybridization techniques and morphology. (ITALY)
47.) Detection of human papillomavirus (HPV) DNA in human prostatic tissues by polymerase chain reaction (PCR). (USA)
48.) High-risk human papillomavirus types in cytologically normal cervical scrapes from Kenya. (KENYA)
49.) Detection of type specific human papillomavirus (HPV) DNA in cervical cancers of Indian women. (INDIA)
50.) Natural history of cervical human papillomavirus lesions. (JAPAN)
51.) Detection of human papillomavirus types in cervical lesions of patients from Taiwan by the polymerase chain reaction. (TAIWAN)
52.) Human papillomaviruses in cervical cancer I. HPV-16 and 18 predominate in the Greek population. (TAIWAN-CHINA) 53.) The prevalence of cervical infection with human papillomaviruses and cervical dysplasia in Alaska Native women. (ALASKA)
54.) Detection of human papillomaviruses in exfoliated cervicovaginal cells by in situ DNA hybridization analysis. (TAIWAN)
55.) Detection and typing of human papillomavirus in cervical specimens of Turkish women. (TURKEY)
56.) Prevalence of human papillomavirus DNA in cervical tissue. Retrospective analysis of 855 cervical biopsies. (GERMANY)
57.) Prevalence of human papillomavirus DNA in female cervical lesions from Rio de Janeiro, Brazil. (BRAZIL)
58.) Prevalence of human papilloma virus 16 or 18 in cervical cancer in Hualien, eastern Taiwan. (TAIWAN)
59.) Human papillomavirus types 52 and 58 are prevalent in cervical cancers from Chinese women. (CHINA)
60.) Human papillomavirus infection and risk determinants for squamous intraepithelial lesion and cervical cancer in Japan. (JAPAN)
61.) Detection and typing of human papillomavirus in cervical carcinomas in Russian women: a prognostic study. (RUSSIA)
62.) Serologic response to human papillomavirus type 16 (HPV-16) virus-like particles in HPV-16 DNA-positive invasive cervical cancer and cervical intraepithelial neoplasia grade III patients and controls from Colombia and Spain. (COLOMBIA, SPAIN)
63.) Detection of human papillomavirus-related oral verruca vulgaris among Venezuelans. (VENEZUELA)
64.) Oncogenic association of specific human papillomavirus types with cervical neoplasia. (USA, PERU and BRAZIL)
65.) Chromosome fragility in lymphocytes of women with cervical uterine lesions produced by human papillomavirus. (ECUADOR)
66.) Multifocal papilloma virus epithelial hyperplasia [see comments] (GUATEMALA)
67.) Genital human papillomavirus infection in Panama City prostitutes. (PANAMA)
68.) Risk factors for genital papillomavirus infection in populations at high and low risk for cervical cancer. (PANAMA)
69.) Demonstration of multiple HPV types in normal cervix and in cervical squamous cell carcinoma using the polymerase chain reaction on paraffin wax embedded material. (ENGLAND)
70.) Morphological correlation of human papillomavirus infection of matched cervical smears and biopsies from patients with persistent mild cervical cytological abnormalities. (ENGLAND)
71.) Epidermodysplasia verruciformis in Africans. (SOUTH AFRICA)
72.) Transmissibility and treatment failures of different types of human papillomavirus. (ISRAEL)
73.) High frequency of detection of epidermodysplasia verruciformis-associated human papillomavirus DNA in biopsies from malignant and premalignant skin lesions from renal transplant recipients. (THE NETHERLANDS)
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1.) Detection and typing of human papillomaviruses by polymerase chain reaction in cervical scrapes of Croatian women with abnormal cytology. (CROATIA)
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Author
Grce M; Husnjak K; Magdi´c L; Ilijas M; Zlacki M; Lepusi´c D; Lukac J;
Hodek B; Grizelj V; Kurjak A; Kusi´c Z; Paveli´c K
Address
Ruder Boskovi´c Institute, Division of Molecular Medicine, Zagreb, Croatia.
grce@olimp.irb.hr
Source
Eur J Epidemiol, 13(6):645-51 1997 Sep
Abstract
The association between certain human papillomaviruses (HPV) and cervical
intraepithelial neoplasia (CIN) is well documented, but still unknown among
Croatian women. In 1995, women between the age of 17 and 64 with
cytomorphologically abnormal smears (CIN I-IV) were tested for the presence
of HPV. Consensus and specific primers were used in the polymerase chain
reaction (PCR) to detect the most common types: 6, 11, 16, 18, 31 and 33,
as well as the unknown-risk HPV types (HPV X). Out of 379 specimens, 163
(43%) contained one or more HPV types. Coinfection with different HPV types
in the same sample was observed in 16 cases. Beside low-risk HPV 6/11 (25.8%)
the most frequently observed types were high-risk HPV types 16 (20.2%) and
31 (17.8%). Globally, the HPV positivity rate declines with age. The
presence of HPV DNA significantly increased from 35.5 to 61.1% along with
the severity of the cervical intraepithelial neoplasia (CIN I-IV). HPV type
6/11 was strongly associated with CIN I (33.8%), HPV type 31 with CIN II
(22.9%), and HPV type 16 with CIN III (50%).

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2.) Risk factors for HPV DNA detection in middle-aged women. (FRANCE)
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Author
Mu~noz N; Kato I; Bosch FX; Eluf-Neto J; De Sanjos´e S; Ascunce N; Gili M;
Izarzugaza I; Viladiu P; Tormo MJ; Moreo P; Gonzalez LC; Tafur L;
Walboomers JM; Shah KV
Address
Unit of Field and Intervention Studies, International Agency for Research
on Cancer, Lyon, France.
Source
Sex Transm Dis, 23(6):504-10 1996 Nov-Dec
Abstract
BACKGROUND AND OBJECTIVES: Strong epidemiologic evidence indicates that
human papillomavirus (HPV) is the main etiologic factor of cervical cancer.
A few cohort studies suggest that most HPV infections are transient in
young women and that persistent HPV infections are more common in older
women. Little is known about the determinants of persistent HPV infections.
The present study was aimed at increasing our knowledge about these
determinants. GOALS: To identify risk factors for genital HPV DNA detection
among cytologically normal middle-aged women. STUDY DESIGN: Eight hundred
ten women who participated as control subjects in three case-control
studies on cervical cancer in Spain, Colombia, and Brazil were included in
this study. After an interview, women underwent a gynecologic examination
with collection of exfoliated cells for a Papanicolaou smear and HPV DNA
detection. Human papilloma virus DNA was detected by polymerase chain
reaction (PCR)-based hybridization techniques. RESULTS: The HPV positivity
rate was 10.5% in the whole population, but was higher in the areas with
high incidence of cervical cancer (17% in Brazil and 13% in Colombia) than
in Spain (4.9%), which is a low-risk area for cervical cancer. Age was
related to the prevalence of HPV DNA in Brazil, but not in Spain and
Colombia. In univariate analyses in all three countries, the prevalence of
HPV DNA was positively associated with the number of lifetime sexual
partners and inversely associated with the levels of family income and with
age at first sexual intercourse. There was four times increase in the odds
ratio (OR) of HPV infection in women who had six or more lifetime sexual
partners compared with those with one or less. The use of any kind of
contraceptive tended to decrease the OR for HPV detection. Their ORs ranged
from 0.44 (barrier methods) to 0.48 (oral contraceptives). In Spain and
Colombia, antibodies against Chlamydia trachomatis were positively
associated with the prevalence of HPV DNA. In a final multivariate model,
the positive associations with lifetime number of sexual partners,
socioeconomic status, and C. trachomatis persisted. CONCLUSIONS: These
results support the sexual transmission of HPV and suggest that
socioeconomic status and antibodies to C. trachomatis are independent
predictors of HPV detection in middle-aged cytologically normal women.

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3.) Human papillomavirus 16 and 18 infection of the uterine cervix in women
with different grades of cervical intraepithelial neoplasia (CIN). (SLOVENIA)
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Author
Takac I; Marin J; Gorisek B
Address
Gynecology and Perinatology Clinic, Maribor Teaching Hospital, Slovenia.
Source
Int J Gynaecol Obstet, 61(3):269-73 1998 Jun
Abstract
OBJECTIVE: To evaluate the frequency of human papillomavirus (HPV) 16 and
18 infection in patients with different grades of cervical intraepithelial
neoplasia (CIN). METHOD: Five-hundred and five patients with CIN, referred
for conization, were included in this study. Before conization, cytological
material for in situ hybridization was obtained from the uterine cervix to
detect the presence of HPV 16 and 18 infection. RESULT: Among all patients
with CIN, 82 (16.2%) were solely HPV 16 and 51 (10.1%) were solely HPV 18
positive. There were 133 patients (26.3%) positive for HPV 16 or HPV 18 and
31 patients (6.1%) were positive for both viral types, giving an overall
HPV 16/18 infection rate of 32.4%. There were 15 (55.5%) HPV 16 or HPV 18
positive patients with CIN 1, 45 (33.8%) HPV 16 or HPV 18 positive patients
with CIN 2 and 104 (30.2%) HPV 16 or HPV 18 positive patients with CIN 3.
CONCLUSION: In patients with CIN 1, HPV 16 and 18 infection was more
frequent than in patients with CIN 2, but the difference was not
significant. Patients with CIN 2 were infected slightly more frequently,
but not significantly, than patients with CIN 3. On the other hand,
patients with CIN 1 were significantly more frequently infected than
patients with CIN 3.

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4.) HPV 16 infection and progression of cervical intra-epithelial
neoplasia: analysis of HLA polymorphism and HPV 16 E6 sequence variants. (AMSTERDAM)
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Author
Bontkes HJ; van Duin M; de Gruijl TD; Duggan-Keen MF; Walboomers JM;
Stukart MJ; Verheijen RH; Helmerhorst TJ; Meijer CJ; Scheper RJ; Stevens
FR; Dyer PA; Sinnott P; Stern PL
Address
Department of Pathology, Free University Hospital, Amsterdam, The
Netherlands.
Source
Int J Cancer, 78(2):166-71 1998 Oct 5
Abstract
High-risk human papillomavirus (HPV) infection plays an important role in
cervical intra-epithelial neoplasia (CIN), but HPV infection alone is not
sufficient for progression to cervical cancer. Several lines of evidence
suggest that cellular immune surveillance is important in the control of
HPV infection and the development of CIN. The presentation to T cells of
target viral peptides in the context of HLA molecules is influenced by the
genetic polymorphisms of both HPV and HLA and thereby influences the host
immune response and clinical outcome of HPV infection. HLA class I and II
polymorphism in susceptibility for HPV 16 infection, development and
progression of CIN was analyzed in a group of 118 patients participating in
a prospective study of women with initial abnormal cytology. Patients were
stratified according to HPV status and course of the disease. HLA-B*44
frequency was increased in the small group of patients with a lesion that
showed clinical progression during follow-up [OR = 9.0 (4.6-17.5), p =
0.007]. HLA-DRB1*07 frequency was increased among HPV 16-positive patients
compared with patients who were negative for all HPV types [OR = 5.9
(3.0-11.3), p = 0.02]. Our results are consistent with the immunogenetic
factors associated with disease progression being different from those
associated with susceptibility to HPV 16 infection. Sequencing of the HPV
16 E6 and E7 open reading frames of a subset of these patients (n = 40)
showed the frequency of HPV 16 variants to be similar to other studies.
However, there was no significant correlation between variant incidence and
disease progression or viral persistence and no significant correlation
with any HLA allele. It appears that multiple HLA types can influence HPV
16-associated cervical dysplasia but the role of HPV 16 variants in disease
progression and susceptibility in relation to HLA polymorphism remains
unclear.

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5.) HPV prevalence among Mexican women with neoplastic and normal
cervixes. (MEXICO)
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Author
Torroella-Kouri M; Morsberger S; Carrillo A; Mohar A; Meneses A; Ibarra M;
Daniel RW; Ghaffari AM; Solorza G; Shah KV
Address
Instituto Nacional de Cancerologia, San Fernando, Tlalpan, Mexico, DF.
Source
Gynecol Oncol, 70(1):115-20 1998 Jul
Abstract
Genital human papillomavirus (HPV) infection is causally linked to cervical
cancer, yet little is known regarding HPV prevalence in cancerous and
normal women in Mexico, a country with a high cervical cancer incidence. We
studied 185 Mexican women among the patients attending gynecological
outpatient clinics in four hospitals in Mexico City. Each woman had a Pap
smear, a colposcopy, and, when necessary, a biopsy. HPVs were identified by
a consensus-primer-based polymerase chain reaction (PCR) assay. HPV was
detected in 87% of 69 cancers, 83% of 24 high-grade squamous
intraepithelial lesions (HGSILs), 33% of 21 low-grade squamous
intraepithelial lesions (LGSILs), and 17% of 71 normals. Twenty-one of the
32 HPV types tested were detected at least once. The ratio of
high-risk:low-risk types was 87:6 in HGSILs and cancers, compared to 11:8
for LGSILs and normals. In invasive cancers, HPV types found at the highest
frequency were, in descending order: HPV-16, -18, and -45, followed by -39,
-59, and -58 with the same frequency. HPV-16 and related types were present
in 52% of the cancer cases, as well as in 79% of HGSILs, and HPV-18 and
related types were present in 36% of the cancers but in only 12.5% of the
HGSILs. HPV-16 was predominant in squamous carcinomas, and HPV-18 and
related types were predominant in adenosquamous carcinoma. Both biopsies
and scrapes were tested for HPVs in 63 women, all of them with cervical
neoplasia. Identical HPV results were obtained in 89% of the samples, but
additional types were often identified in scrapes. HPV prevalence and type
distribution in cervical cancer in Mexico was similar to the reported
worldwide, as well as in other Latin American countries.

===================================================================
6.) Cigarette smoking and high-risk HPV DNA as predisposing factors for
high-grade cervical intraepithelial neoplasia (CIN) in young Brazilian women. (BRAZIL)
===================================================================
Author
Roteli-Martins CM; Panetta K; Alves VA; Siqueira SA; Syrj¨anen KJ; Derchain
SF
Address
Department of Obstetrics and Gynecology, Campinas State University
(UNICAMP), Brazil.
Source
Acta Obstet Gynecol Scand, 77(6):678-82 1998 Jul
Abstract
BACKGROUND: This cross-sectional study was designed to evaluate the role of
cigarette smoking and high-risk HPV types as risk factors of CIN 2 and 3 in
young, sexually active Brazilian women. MATERIALS AND METHOD: A series of
100 consecutive women with abnormal Pap smears were recruited, subjected to
colposcopy, punch biopsy, and questionnaire for their social, sexual and
reproductive factors. Of these, 77 women between 20 and 35 years of age
(median 26.5 years) with biopsy-confirmed CIN 1 or CIN 2 and 3, were
enrolled in this study. Representative samples from the exocervix and
endocervix were obtained for HPV testing with the Hybrid Capture HPV-DNA
assay, including the probes for the oncogenic HPV types (16, 18, 31, 33,
35, 45, 51, 52 and 56). RESULTS: The overall rate of CIN 2 and 3 was 23/77
(29.8%). The women with CIN 1, 2 and 3 did not differ from each other with
regard to their age, race, schooling, marital status, lifetime number of
sexual partners, age at first intercourse, use of oral contraceptives, or
parity. However, current cigarette smoking was strongly associated with CIN
2 and 3 (p<0.001), and among smokers, the risk of high-grade CIN increased
in parallel with the time of exposure (years of smoking) (p=0.07). HPV-DNA
of the oncogenic types was detected in 43 (56%) women, the risk of being
HPV DNA-positive was significantly higher in CIN 2 and 3 as compared with
CIN 1 (p=0.037). Importantly, the prevalence of high-risk HPV types was
significantly higher in cigarette smokers than in non-smokers (p=0.046).
CONCLUSIONS: The results indicate that the severity of CIN lesions was
clearly related to two fundamental risk factors: 1) high-risk HPV types,
and 2) current cigarette smoking. These two risk factors were closely
interrelated in that the high-risk HPV types were significantly more
frequent in current smokers than in non-smokers, suggesting the possibility
of a synergistic action between these two risk factors in cervical
carcinogenesis.

===================================================================
7.) Prevalence of human papillomavirus infection in premalignant and
malignant lesions of the oral cavity in U.K. subjects: a novel method of
detection. (LONDON)
===================================================================
Author
Elamin F; Steingrimsdottir H; Wanakulasuriya S; Johnson N; Tavassoli M
Address
RCS Department of Dental Sciences, King's College School of Medicine and
Dentistry, Rayne Institute, London, U.K.
Source
Oral Oncol, 34(3):191-7 1998 May
Abstract
To evaluate the possible role of human papillomavirus (HPV) in oral
neoplasms, 28 oral squamous cell carcinomas (SCC) and 12 potentially
malignant lesions were analysed for the presence of HPV DNA. A nested
polymerase chain reaction (PCR) approach, using two sets of HPV consensus
primers to the L1 region, was used, which was able to detect a broad
spectrum of HPV types. HPV DNA was detected in 14/28 (50%) carcinomas and
4/12 (33%) precancerous lesions. A novel approach based on labelling the
PCR products with 32P and the separation of radioactively labelled products
on an 8% polyacrylamide gel increased the sensitivity of the detection and
enabled the identification of the HPV types. The typing of HPV was
subsequently confirmed by direct DNA sequencing. HPV 6 and HPV 16 were the
only HPV types detected and seven tumours harboured both types. Our results
suggest that HPVs may be an important aetiological factor in the
development of oral cancer. The detection procedure ensured sensitivity and
consistency of the detection of low copy numbers of the virus DNA. The
presence of HPV in 33% of premalignant tissues suggests that HPV infection
may be an early event in the malignant transformation of oral SCC. There
was no statistically significant association between viral infection and
tumour grade or stage.

===================================================================
8.) Causes of cervical cancer in the Philippines: a case-control study. (PHILLIPINES)
===================================================================
Author
Ngelangel C; Mu~noz N; Bosch FX; Limson GM; Festin MR; Deacon J; Jacobs MV;
Santamaria M; Meijer CJ; Walboomers JM
Address
Department of Medicine, Philippine General Hospital, University of the
Philippines, Manila.
Source
J Natl Cancer Inst, 90(1):43-9 1998 Jan 7
Abstract
BACKGROUND: Among the numerous human papillomavirus (HPV) types, only types
16 and 18 have been formally classified as human carcinogens. To evaluate
the associations of 33 HPV types and other risk factors with squamous cell
carcinoma and adenocarcinoma of the cervix, we performed a hospital-based,
case-control study in the Philippines. METHODS: The study included 356 case
subjects who had histologically confirmed cervical cancer (323 incident
cases of squamous cell carcinoma and 33 incident cases of
adenocarcinoma/adenosquamous carcinoma) and 381 control subjects.
Information on risk factors was obtained by personal interview. HPV DNA was
detected in exfoliated cervical cells and biopsy specimens by use of a
polymerase chain reaction assay. RESULTS: HPV DNA was detected in 93.8% of
case subjects with squamous cell carcinoma and in 90.9% of case subjects
with adenocarcinoma/adenosquamous carcinoma compared with 9.2% of control
subjects, giving age-adjusted odds ratios of 156 (95% confidence interval
[CI] = 87-280) for squamous cell carcinoma and 111 (95% CI = 31-392) for
adenocarcinoma/adenosquamous carcinoma. Fifteen different HPV types were
detected in squamous cell carcinoma, and six different HPV types were
detected in adenocarcinoma/adenosquamous carcinoma. Among HPV types other
than types 16 and 18, the associations of HPV with risk of squamous cell
carcinoma were strongest for HPV45. In addition to HPV, high parity, low
socioeconomic status, and smoking were also associated with both types of
cervical cancer. CONCLUSIONS: As has been shown for squamous cell
carcinoma, HPV is the central cause of adenocarcinoma/adenosquamous
carcinoma of the uterine cervix. The observed associations of less
prevalent HPV types with cervical cancer have important implications for
cervical cancer prevention strategies.

===================================================================
9.) Novel HPV types present in oral papillomatous lesions from patients
with HIV infection. (GERMANY)
===================================================================
Author
V&uml;olter C; He Y; Delius H; Roy-Burman A; Greenspan JS; Greenspan D; de
Villiers EM
Address
Division for Tumorvirus Characterizatiom, Deutsches Krebsforschungszentrum,
Heidelberg, Germany.
Source
Int J Cancer, 66(4):453-6 1996 May 16
Abstract
Patients infected with the human immunodeficiency virus (HIV) often develop
multiple papillomatous lesions of the oral cavity. In the present study, a
total of 67 biopsies from benign oral lesions were analyzed for the
presence of human papillomavirus (HPV) DNA using Southern-blot
hybridization in combination with a polymerase chain reaction designed to
detect all known HPV types, as well as unidentified types. These samples,
collected at random from a high-risk population, were subsequently divided
into 57 biopsies originating from patients with confirmed HIV infection and
10 biopsies from patients with unknown HIV status. Each sample was
amplified with 7 different combinations of degenerate primers. All
amplified products were sequenced. HPV DNA sequences were detected in 67%
(45/67) of the samples. HPV 7 (19%) and HPV 32 (28%) were the predominant
HPV types. HPV 32 was present in 2/4 fibromas tested. Two new HPV types,
HPV 72 and HPV 73, were identified in oral warts with atypia. The complete
genomes of these viruses were cloned and sequenced. Other HPV types
detected were HPV 2a, HPV 6b, HPV 13, HPV 16, HPV 18, HPV 55, HPV 59 and
HPV 69.

===================================================================
10.) HPV-types, cytological and histopathological findings in three groups
of women with possible HPV-related disease. (SWEDEN)
===================================================================
Author
Frederiksson A; Larson B; Persson E; Auer G; Johansson B; Kalantari M; von
Krogh G; Silfversw&uml;ard C
Address
Department of Obstetrics and Gynaecology, Karolinska Hospital, Stockholm,
Sweden.
Source
Acta Obstet Gynecol Scand, 75(6):556-62 1996 Jul
Abstract
OBJECTIVE. The aim of this investigation was to study three groups of women
presenting with possible HPV-infection with regard to HPV-types and
cervical dysplasia. METHODS. Eighty women were included. Eighteen of them
were present partners to men with condylomas, 20 had clinical vulvar
HPV-lesions and 42 were referred due to an abnormal PAP-smear. Samples for
HPV-analysis by PCR-technique were taken from the vulva, the portio and the
cervical canal. A universal HPV-primer as well as specific primers for HPV
6/11, 16, 18, 31, and 33 were utilized. PAP-smears were taken as well as
biopsies from cervix/portio. RESULTS. Seventy-eight percent had HPV-DNA
identified. Sixty-seven percent of those with HPV 16 and/or 18 had
dysplasia verified by histopathology and 50% of those with 31 and/or 33.
Twenty of 21 women with dysplasia had HPV 16, 18, 31 and/or 33 identified.
One woman with dysplasia was HPV-negative. Histopathologically verified CIN
were diagnosed in all groups investigated. Women referred for suspicion of
CIN significantly more often had HPV detected at the cervix/portio. HPV
6/11 was mostly found in women with condylomas. Apart from this the
occurrence of the different HPV types were alike in the three groups.
CONCLUSION. Infection with HPV is a process and the usefulness of different
diagnostic methods seems to depend on when during the course of the disease
they are used. HPV-findings in women with dysplasia were all associated
with oncogenic virus-types. High-risk virus was often found simultaneously
with low-risk virus indicating a covariation in the acquisition of the
different HPV-types.

===================================================================
11.) A general primer GP5+/GP6(+)-mediated PCR-enzyme immunoassay method
for rapid detection of 14 high-risk and 6 low-risk human papillomavirus
genotypes in cervical scrapings. (AMSTERDAM)
===================================================================
Author
Jacobs MV; Snijders PJ; van den Brule AJ; Helmerhorst TJ; Meijer CJ;
Walboomers JM
Address
Department of Pathology, University Hospital Vrije Universiteit, Amsterdam,
The Netherlands.
Source
J Clin Microbiol, 35(3):791-5 1997 Mar
Abstract
Two cocktails of digoxigenin-labeled human papillomavirus (HPV)
type-specific oligonucleotide probes and an enzyme immunoassay (EIA) were
used as a basis to developed a group-specific detection method for 14
high-risk (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and
68) and 6 low-risk (types 6, 11, 40, 42, 43, and 44) HPVs, following a
general primer GP5+/bioGP6(+)-mediated PCR. The sensitivity of this
high-risk/low-risk (HR/LR) HPV PCR-EIA ranged from 10 to 200 HPV copies,
depending on the HPV type. Comparison of HR/LR HPV PCR-EIA with radioactive
Southern blot hybridization using a general probe on the same PCR products
derived from 417 cytomorphologically abnormal cervical scrapings resulted
in an overall agreement of 96% between the two methods. Complete
concordance between group-specific HR/LR detection and individual typing
results for both single and multiple infections indicate the strong
specificity of this HR/LR HPV PCR-EIA. Multiple infections could be
predicted by comparing PCR-EIA optical density values of the cocktail
probes with one of the individual oligonucleotide probes. This novel HR/LR
PCR-EIA allows accurate and rapid identification of high-risk and low-risk
HPV types in cervical scrapings and will facilitate HPV detection in HPV
mass-screening programs.

===================================================================
12.) Prevalence of antibodies to human papillomavirus (HPV) type 16
virus-like particles in relation to cervical HPV infection among college
women. (USA)
===================================================================
Author
Viscidi RP; Kotloff KL; Clayman B; Russ K; Shapiro S; Shah KV
Address
Eudowood Division of Infectious Diseases, Department of Pediatrics, Johns
Hopkins University School of Medicine, Baltimore, Maryland, USA.
rviscidi@welchlink.welch.jhu.edu
Source
Clin Diagn Lab Immunol, 4(2):122-6 1997 Mar
Abstract
A human papillomavirus type 16 (HPV-16) virus-like particle (VLP)-based
enzyme-linked immunosorbent assay (ELISA) was used to measure serum
antibody to capsid proteins in 376 sexually active college women who were
also screened for the presence of genital HPVs by PCR and interviewed for
demographic and behavioral risk factors for HPV infection. The
seroprevalence was 46% in women with HPV-16 DNA in the genital tract. The
corresponding values for women who harbored other HPV types or no HPV in
the genital tract were 30 and 19%, respectively (HPV-16 group versus no-HPV
group; odds ratio [OR], 3.7; 95% confidence interval [CI], 1.5 to 8.9). The
antibody response was significantly higher among women with a high viral
load than among those with a low viral load (median optical density value,
0.838 versus 0.137, P = 0.009). Comparable levels of seroreactivity were
observed among women infected with HPV types distantly or closely related
genetically to HPV-16. Seroreactivity was significantly associated with an
age of 25 to 30 years (OR, 2.3; 95% CI, 1.2 to 4.4), three or more lifetime
sexual partners (OR, 2.9; 95% CI, 1.1 to 10), and history of a sexually
transmitted disease other than HPV (OR, 3.1; 95% CI, 1.5 to 6.3). The
percent seropositivity increased linearly with number of lifetime sexual
partners until reaching a plateau at 35% for women with more than six
partners (chi for linear trend, P < 0.001). The low sensitivity of HPV-16
VLP-based ELISA may limit the usefulness of the assay as a diagnostic test
for HPV-16 infection. However, the assay appears to have adequate
specificity and should be useful as an epidemiological marker of HPV-16
infection and sexual behavior.

===================================================================
13.) Detection of human papillomavirus mRNA and cervical cancer cells in
peripheral blood of cervical cancer patients with metastasis. (TAIWAN)
===================================================================
Author
Pao CC; Hor JJ; Yang FP; Lin CY; Tseng CJ
Address
Department of Biochemistry, Chang Gung College of Medicine and Technology,
Taipei, Taiwan. ccpao@cguaplo.cgu.edu.tw
Source
J Clin Oncol, 15(3):1008-12 1997 Mar
Abstract
PURPOSE: To determine the presence of cervical cancer cells in circulating
peripheral blood of stage IVb cervical cancer patients with metastasis to
distant organs. PATIENTS AND METHODS: Cervical cancer tissue from 15 stage
IVb cervical cancer patients with metastasis were analyzed for the presence
of human papillomavirus (HPV) type 16 DNA by nested polymerase chain
reaction (PCR). The presence of transcriptional products of the HPV type 16
E6-transforming gene in the peripheral blood of the same 15 cancer patients
was analyzed by reverse transcription and PCR. Cervical tissues and
peripheral-blood specimens from 12 normal healthy individuals served as
controls. RESULTS: Thirteen of 15 (86.7%) cervical cancer tissues from same
number of patients were found to contain HPV type 16 DNA. Peripheral-blood
specimens from 12 of 13 (92.3%) cervical HPV DNA-positive patients were
found to contain HPV-specific mRNA detectable by reverse transcription (RT)
and PCR. Cervical tissues from all 12 normal controls were HPV-free. None
of the peripheral-blood specimens from two cervical HPV-negative cancer
patients and 12 normal controls contained detectable amounts of mRNA of HPV
type 16 E6-transforming gene. CONCLUSION: The most likely source of the
HPV-specific mRNA detected in the peripheral blood of cervical cancer
patients with metastasis is the cervical cancer cells derived from or shed
from the cervix. The presence of HPV E6 mRNAs in peripheral blood may be a
sensitive indicator of circulating cervical cancer cells. If PCR positivity
is proven to be able to predict disease progression reliably, these
findings may have clinical applications in the treatment of cervical and
many other cancers.

===================================================================
14.) Human papillomavirus in tissue of bladder and bladder carcinoma
specimens. A preliminary study. (GERMANY)
===================================================================
Author
Ludwig M; K&uml;ochel HG; Fischer C; Ringert RH; Weidner W
Address
Department of Urology, Justus-Liebig-Universit&uml;at, Giessen, Germany.
Source
Eur Urol, 30(1):96-102 1996
Abstract
OBJECTIVE: To evaluate the significance of HPV type 6b, 11, 16 and 18
together with type-specific antibodies in the serum of bladder carcinoma.
METHODS: The prevalence of HPV type 6b, 11, 16 and 18 in bladder tumor,
normal bladder and urethra together with type-specific antibodies in serum
was investigated in 23 patients with bladder cancer and 9 patients with
chronic cystitis. HPV DNA analysis was done by polymerase chain reaction
(PCR). Open reading frames of HPV were expressed in Escherichia coli as
beta-galactosidase fusion proteins. RESULTS: HPV 6b was demonstrated in the
tumor tissue of 6 patients (19%), and in the nonmalignant specimens of 6
further patients (19%). HPV 16/18 was only found in the urethral swabs of 2
patients (6%). Anti-HPV antibodies were positive in 7 patients (22%). There
was no association between the demonstration of HPV 6b and the occurrence
of bladder tumor in this study. CONCLUSION: Though, in this study, HPV was
not associated with bladder cancer, further investigation is necessary to
elucidate the role of HPV 6b in bladder tissue possibly by a
semiquantitative PCR in tissue samples and of anti-HPV antibodies in serum.

===================================================================
15.) Detection of human papillomavirus (HPV) type 47 DNA in malignant
lesions from epidermodysplasia verruciformis by protocols for precise
typing of related HPV DNAs. (JAPAN)
===================================================================
Author
Adachi A; Kiyono T; Hayashi Y; Ohashi M; Ishibashi M
Address
Laboratory of Viral Oncology, Research Institute, Nagoya, Japan.
Source
J Clin Microbiol, 34(2):369-75 1996 Feb
Abstract
Our discovery of human papillomavirus type 47 (HPV47) in benign lesions
from a patient suffering from epidermodysplasia verruciformis prompted us
to examine whether the viral DNA also resided in malignant lesions from the
same patient. By using newly devised protocols for amplifying a group of
epidermodysplasia verruciformis-associated HPV DNAs by PCR and
differentially identifying them by reverse-phase dot blot hybridization, we
demonstrated that HPV47 DNA, but not other HPV DNAs of the group, was
abundant (about 10(3) copies per diploid amount of cell DNA) in DNAs
prepared from three carcinomas. Using DNA from one of these carcinomas, we
also confirmed that DNA of HPV5, HPV14, or HPV21, detected in significant
amounts in DNAs from benign lesions from the patient, were present only in
negligible amounts or not at all. The results suggest the involvement of
HPV47 DNA in tumorigenesis. Furthermore, we demonstrated by the Southern
technique that most, if not all, of the HPV47 DNA consists of either a unit
(or a nongrossly deleted unit) length of the viral genome carrying no (or
no gross) internal rearrangements or tandem repeats. This and other results
obtained by this technique indicated that a considerable amount of the
viral DNA resides as a circular monomer a unit length of the viral genome
in carcinoma cells, while the remainder reside as catenanes, concatemers,
or both. The concatemers were considered more likely to be replicated
without integration into cellular DNA than to be integrated, because no
bands for the corresponding fragments including integration sites were
detected by treatment with restriction enzymes that would have produced
such fragments.

===================================================================
16.) HLA and susceptibility to cervical neoplasia. (NETHERLANDS)
===================================================================
Author
Krul EJ; Schipper RF; Schreuder GM; Fleuren GJ; Kenter GG; Melief CJ
Address
Department of Pathology, Leiden University Medical Center, The Netherlands.
Source
Hum Immunol, 60(4):337-42 1999 Apr
Abstract
The association between cervical neoplasia and certain HLA phenotypes
observed in different studies has not been consistent. By serological
typing, the association between HLA antigens, cervical carcinoma and
cervical intraepithelial neoplasia (CIN) was studied in a group of 172 and
116 patients, respectively. We demonstrated an increased frequency of B63
in patients with HPV types other than HPV 16 or 18, and B55 in patients
that were negative for all HPV types. The association between cervical
carcinoma and DQ3, described in various populations, was not observed in
the present study. However, we confirmed other previously observed
associations between cervical cancer and class II antigens, i.e., a
positive correlation with DR15 irrespective of the HPV status, with DR3 in
patients harboring HPV types other than HPV 16 or 18, and with DR11 among
HPV 16 positive patients. In contrast, a negative correlation between DR13
and HPV positive cervical cancer was observed which suggests protection of
this antigen against HPV-associated cervical cancer. A slight increase of
DR15 and DQ4 antigens was observed in CIN patients, suggesting that these
specific HLA antigens may be important in determining the risk of CIN.

===================================================================
17.) Non-isotopic in situ hybridization of HPV types in cervical
intraepithelial lesions in patients with AIDS. (BRAZIL)
===================================================================
Author
Calore EE; Calore NM; Cavaliere MJ
Address
Department of Pathology, Faculty of Medicine, University of S~ao Paulo,
Brazil. calore@uol.com.br
Source
Arch Gynecol Obstet, 262(1-2):75-9 1998
Abstract
Human papilloma viruses (HPVs), particularly types 16 and 18 have a key
role in the development of preneoplastic and neoplastic lesions of the
uterine cervix. We studied, by non isotopic in situ hybridization using
probes to HPV 6, 11, 16 and 18, cervical biopsies from AIDS patients with
condilomata or cervical intraepithelial neoplasia. There were 32 biopsies
which showed low-grade cervical intraepithelial neoplasia (Lo-CIN); 5
biopsies showed high-grade cervical intraepithelial neoplasia (Hi-CIN). Of
32 Lo-CIN biopsies, 18 (56.3%) were positive for HPV; 7 for HPV 6 and/or 11
(21.9%), 11 for HPV 16 and/or 18 (34.4%) and one for HPV 6 and 18. Of 5
Hi-CIN biopsies 3 were positive for HPV: one for HPV 6 and 2 for HPV 16 or
18. The total positivity was 56.8% (21/37). This result was similar to
those obtained by various other authors studying the general population.

===================================================================
18.) HLA-A2-restricted peripheral blood cytolytic T lymphocyte response to HPV type 16 proteins E6 and E7 from patients with neoplastic cervical
lesions. (GERMANY)
===================================================================
Author
Evans C; Bauer S; Grubert T; Brucker C; Baur S; Heeg K; Wagner H; Lipford GB
Address
Institute for Medical Microbiology, Technical University of Munich, Germany.
Source
Cancer Immunol Immunother, 42(3):151-60 1996 Mar
Abstract
The DNA from human papillomavirus (HPV) can be detected in 90% of cervical
carcinomas. To address whether patients infected with HPV can mount
efficient T cell responses to this pathogen we examined the cytotoxic T
lymphocyte (CTL) response of peripheral blood mononuclear cells (PBMC) from
patients with abnormal genital epithelial cells. PBMC from 11 HLA-A2+
patients were stimulated with CaSki, a cervical carcinoma cell line that is
HPV 16+ and HLA-A2+. The CTL were screened for reactivity to the cervical
carcinoma cell line C33A (HPV-, HLA-A2+) transfected with the HPV 16 E6 or
E7 genes or the plasmid without insert. The CTL of 1 patient showed
particularly strong CaSki and HPV E6 or E7 protein-specific cytotoxicity in
a HLA-A2+-restricted fashion. In contrast, these CTL lysed neither a
vector-only transfectant, the natural killer cell (NK) target, K562 nor the
lymphokine-activated killer cell (LAK) target, Daudi. HLA-A2 restriction
was demonstrated by the lack of recognition of a HLA-A2- CaSki cell line
developed in our laboratory. The CTL line was cloned and 99 clones were
harvested and screened; 51 clones lysed CaSki, of which 17 did not lyse the
A2- CaSki. Of these HLA-A2- restricted clones, 8 did not lyse C33A
transfectants, 6 lysed all C33A transfectants, 3 lysed C33A-E7 only and
none lysed C33A-E6 only. These data imply that, within the bulk CTL line,
HLA-A2-restricted recognition of antigens was restricted to CaSki antigens,
antigens common to cervical carcinoma (CaSki plus C33A), or
HPV-16-E7-derived antigen on the clonal level. The E7-restricted clones
were negative for recognition of known HLA-A2-binding peptides from E7.

===================================================================
19.) Human papilloma virus 16-18 infection and cervical cancer in Mexico: a
case-control study. (MEXICO)
===================================================================
Author
Hern&acute;andez-Avila M; Lazcano-Ponce EC; Berumen-Campos J; Cruz-Vald&acute;ez A;
Alonso de Ru&acute;iz PP; Gon&acute;zalez-Lira G
Address
Centro de Investigaci&acute;on en Salud Poblacional, Instituto Nacional de Salud
P&acute;ublica, Cuernavaca, Morelos, M&acute;exico.
Source
Arch Med Res, 28(2):265-71 1997 Summer
Abstract
Cervical cancer (CC) is one of the principal public health problems in
Mexico. The national mortality rate due to CC was estimated at 21.8 per
100,000 among women over 15 years old during 1994. Despite this high
incidence little is known in Mexico about the risk factors for CC. The
objectives of the study were to evaluate the association between CC and HPV
types 16 and 18 in women living in Mexico City. From August, 1990 to
December, 1992, a case-control study was carried out in the metropolitan
area of Mexico City. HPV 16-18 types were determined in a sample of 148 CC
cases and 204 controls randomly selected from a sample frame representative
of the metropolitan area of Mexico City. Sixty cases corresponded to in
situ CC and 88 cases to the invasive phase. Determination of HPV 16 and 18
types was done by polymerase chain reaction using primers specific to
E6/E7. Results showed that 48.3% of in situ CC cases and 48.8% of invasive
CC cases were positive for HPV 16 while only 13.2% were positive among the
204 controls. Association between HPV 16 infection in the in situ cancer
cases had an estimated odds ratio (OR) of 5.17 (95% CI 2.60-10.51). In the
invasive cervical cancer cases, association between HPV 16 infection and
invasive CC in this sample had an OR of 3.84 (95% CI 2.04-7.22). For the
total sample, the estimated OR was 5.48 (95% CI 3.07-9.62). In the total
sample, those women with a strong positive reaction to PCR were associated
with a large increase in the risk, OR of 38.0 (95% CI 8.66-167.1). The
prevalence the HPV 18 was 6.7%, only observed in the invasive cervical
cancer cases. At present there is general consensus that HPV is the
principal causal agent in C C etiology. This study intends to contribute to
the knowledge concerning the etiology of cervical cancer. However, it is
necessary to consider that the single most effective tool in the reduction
of mortality due to cervical cancer has been the Pap test. Secondary
prevention has proven to be highly effective in other populations, and this
should be viewed as a priority activity for all at-risk populations.
Although a vaccine for HPV may be available in the near future its efficacy
in primary prevention has yet to be demonstrated.

===================================================================
20.) Detection of human papillomavirus (HPV) type 6, 16 and 18 in head and
neck squamous cell carcinomas by in situ hybridization. (CROATIA)
===================================================================
Author
Cerovac Z; Sar&uml;cevi&acute;c B; Kralj Z; Ban J
Address
Ruder Bo&uml;skovic Institute, Department of Molecular Genetics, Zagreb, Croatia.
Source
Neoplasma, 43(3):185-94 1996
Abstract
Seventy seven squamous cell carcinomas (10 oral cavity, 15 tongue, 26
pharynx and 26 larynx), with different grading, were analyzed for the
presence of HPV DNA by in situ hybridization. Positive signals were found
on the nuclei of cancer cells in 25 (32.5%), in the epithelia adjacent to
squamous cell carcinomas in 2 (8.7%), and in the resected margins in 1
(4.3%) case. HPV DNA positive signals were obtained in 42% of laryngeal,
34% of pharyngeal, in 20% of oral, and 20% of tongue carcinomas. Out of 25
HPV positive carcinomas a single HPV type was detected in at least 11
(44%), and double or multiple infection in 9 (36%) cases; altogether, HPV 6
DNA was determined in 15 (60%), and HPV 16 and/or 18 DNA in 17 (68%) head
and neck tumors. The detection rate of HPV 6 was lower than of HPV 16
and/or 18 for tumors in oral cavity, tongue and larynx. Out of 25 HPV DNA
positive carcinomas 21% were graded as G1, 27% as G2, and 44% were G3. The
results indicate that HPV may be involved in the pathogenesis of head and
neck squamous cell carcinomas.

===================================================================
21.) Prevalence of human papillomavirus infection in women attending a
sexually transmitted disease clinic. (JAPAN)
===================================================================
Author
Kubota T; Ishi K; Suzuki M; Utsuno S; Igari J
Address
Department of Obstetrics and Gynecology, Juntendo University, Juntendo
Urayasu Hospital, Chiba, Japan.
Source
Kansenshogaku Zasshi, 73(3):233-8 1999 Mar
Abstract
The purpose of this study was to determine the prevalence of infection due
to human papillomavirus (HPV) types of high and intermediate oncogenic
risk, which was most frequently associated with uterine cervical neoplasia.
The subjects were 236 prostitutes who visited a sexually transmitted
diseases (STD) clinic in a metropolitan area in 1998. Another 95 women who
visited a university hospital were selected as a normal control group. A
swab sample collected from the uterine cervix and external os was subjected
to hybrid capture assays for low-oncogenic-risk HPV types (HPV A; including
types 6, 11, 42, 43 and 44) and high- and intermediate-oncogenic-risk HPV
types (HPV B; including 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and
68). Chlamydia trachomatis and Neisseria gonorrhoeae. Fisher's exact test
was used for statistical analyses. Among the microorganisms tested, the
positive rate for HPV B was the highest both in the women attending the STD
clinic (STD group) and in the control group. The positive rate for HPV B in
the STD group was 47.5% (112 of 236), and this was significantly higher
than the 5.3% (5 of 95) in the control group (p < 0.0001). These findings
suggest that HPV examination is recommended for women who visit an STD
clinic to assess the future risk of cervical neoplasia.

===================================================================
22.) Demonstration of multiple HPV types in laryngeal premalignant lesions
using polymerase chain reaction and immunohistochemistry. (ITALY)
===================================================================
J Med Virol 1999 Sep;59(1):110-116

Azzimonti B, Hertel L, Aluffi P, Pia F, Monga G, Zocchi M, Landolfo S,
Gariglio M
Department of Medical Sciences, Medical School of Novara, University of
Piemonte Orientale "A. Avogadro," Novara, Italy.

Recent evidence has shown that human papillomavirus (HPV) is involved in
both the development of carcinoma and in premalignant mucosal lesions of
the oral cavity. This study examined the relationship of HPV infection to
some pathological features in precancerous lesions of the larynx, not
examined extensively so far. Fifty formalin-fixed paraffin-embedded tissue
sections containing human laryngeal precancerous lesions were screened for
the presence of HPV infection by polymerase chain reaction, and for capsid
protein expression by immunohistochemistry with polyclonal antibody
directed against the L1 protein. The presence of HPV DNA was detected in 28
of 50 specimens (56%), including 9/12 cases with mild dysplasia (75%), 3/6
cases with moderate dysplasia (50%), and 7/11 cases with severe dysplasia
(64%). Multiple HPV infections, containing two or three types, were
detected in 17 of the 28 HPV-positive lesions (60%). Of 21 cases with
keratosis and no dysplasia, 11 were positive for HPV DNA (52%) and 4 showed
L1 staining (36%). By contrast, L1 positivity was revealed only in two
lesions with moderate dysplasia, confirming that fully productive HPV
infection is strictly dependent on epithelial differentiation and surface
keratinization. The probability that HPV is a cofactor in the malignant
progression of these lesions is suggested by the fact that 3/4 patients who
developed cancer within 50 months were positive for HPV DNA. Copyright 1999
Wiley-Liss, Inc.

===================================================================
23.) Adenocarcinoma of the uterine cervix in Ireland and Sweden: human
papillomavirus infection and biologic alterations. (IRELAND AND SWEDEN)
===================================================================
Mod Pathol 1999 Jul;12(7):675-82

Skyldberg BM, Murray E, Lambkin H, Kelehan P, Auer GU
Department of Oncology-Pathology, Cancer Center Karolinska, Huddinge
Hospital, Karolinska Institute, Stockholm, Sweden. Barbro.Skyldberg@cck.ki.se

Paraffin-embedded samples from cervical adenocarcinomas, 19 cases from
Irish patients and 19 cases from Swedish patients, were analyzed by
polymerase chain reaction for the presence of infection with human
papillomavirus (HPV). The results were compared with DNA ploidy,
proliferation activity, and p53 and p21/WAF1 expression. The studies were
performed to discover whether high-risk HPV infection in adenocarcinomas of
the uterine cervix is associated with an increased proliferative activity
and genomic instability. The results show that the majority (84.6%) of
patients 59 years of age or younger showed HPV infection. The overall
prevalence of HPV DNA was 60.5%, with the high-risk types, 16 and 18, the
most frequent. HPV-16 had a prevalence of 23.7% (9 of 38), and HPV-18 had a
prevalence of 26.3% (10 of 38). The HPV-positive tumors predominantly
showed a tetraploid DNA distribution pattern, whereas HPV-negative tumors
more frequently showed highly scattered aneuploid DNA profiles. Both
HPV-positive and HPV-negative cases displayed high proliferative activity,
as indicated by high Ki-67 and cyclin A immunoreactivity. Tumor suppressor
gene analysis detected low p53 expression and high p21/WAF1 expression in
HPV-positive patients and high p53 expression without simultaneously
increased p21/WAF1 (indicative of mutated p53) in HPV-negative cases in the
groups of women older than 59 years of age.

===================================================================
24.) Risk factors for high-risk type human papillomavirus infection among
Mexican-American women. (USA-MEXICO)
===================================================================
Cancer Epidemiol Biomarkers Prev 1999 Jul;8(7):615-20

Giuliano AR, Papenfuss M, Schneider A, Nour M, Hatch K
Arizona Cancer Center, University of Arizona, Tucson 85724, USA.
agiuliano@azcc.arizona.edu

Minority women in the United States experience a disproportionately high
burden of the more than 2 million yearly cases of squamous intraepithelial
lesions of the cervix. Risk factors for squamous intraepithelial lesions of
the cervix are infection with the sexually acquired human papillomavirus
(HPV), an early age at first intercourse, history of multiple sexual
partners, oral contraceptive use, high parity, lower socioeconomic status,
poor diet, immunosuppression, and promiscuous male sexual partners.
Although Hispanics are the largest growing minority population in the
United States, few HPV risk factor studies have either included or focused
on Hispanics in the United States. To determine risk factors for HPV
infection among Mexican-American women, we conducted a cross-sectional
study from 1992-1995. Nine hundred and seventy-one women, 18-47 years of
age, with cytology results were included in this analysis. Overall, 13.2%
of participants were HPV positive by the Hybrid Capture tube method for
high-risk types 16, 18, 31, 33, 35, 45, 51, 52, or 56. Age [adjusted odds
ratio (AOR) = 0.3 for ages >36 years compared with ages 18-20] and duration
of oral contraceptive use (AOR = 0.4 for > or =4 years relative to
nonusers) were inversely associated with these high-risk types of HPV
infection. Marital status (AOR = 1.9 among single women compared with
married) and lifetime number of sexual partners (AOR = 2.3 for women > or
=5 partners relative to monogamous women) were positively associated with
an increased risk. Participants born in Mexico were significantly (P <
0.05) older, had fewer sex partners, and older age at first intercourse.
Despite this lower behavioral risk profile, women born in Mexico were
significantly more likely (AOR = 1.9; CI = 1.2-3.2) to have an HPV
infection compared with United States-born, Mexican-American women after
adjustment for potential confounders. Collectively, these results suggest
that an unmeasured factor, such as the sexual behavior of the male partner,
may be influencing HPV risk. Further research is needed to define this
factor and to assess cultural norms of sexual behavior.

===================================================================
25.) Many different papillomaviruses have low transcriptional activity in
spite of strong epithelial specific enhancers. (SINGAPORE)
===================================================================
J Gen Virol 1999 Jul;80 ( Pt 7):1715-24

Sailaja G, Watts RM, Bernard HU
Institute of Molecular and Cell Biology, National University of Singapore,
Republic of Singapore.

Transcription of the E6-E7 genes of human papillomavirus type 11 (HPV-11),
HPV-16 and HPV-18 is specific to epithelial cells. This mechanism
originates from synergism between different transcription factors such as
AP-1, NFI and Sp1, which occur in many different cell types, but whose
activity is biased in favour of epithelial cells. In this study, the
transcriptional regulation of 14 different papillomavirus types in the
absence of the viral E2 transcription factor was compared. Genital HPV
types, including high-risk, low-risk and common wart-associated HPVs, were
found to have strong epithelial specific enhancers, irrespective of mucosal
or skin target cell and pathology. Skin specific non-genital HPVs, like
HPV-1 and HPV-8, as well as bovine papillomavirus type 4 (BPV-4), had much
lower enhancer activity. Contiguous genomic segments including the enhancer
and the E6 promoter of genital as well as non-genital papillomaviruses
generally had very low transcriptional activities, presumably due to
silencers between enhancer and promoter sequences. This generalization
applies to all cell types tested in spite of significant quantitative
differences between the cervical carcinoma-derived cell line HeLa, the
skin-derived cell line HaCat, undifferentiated and differentiated primary
keratinocytes. The only enhancer with activity in fibroblasts was
identified in BPV-1, apparently a reflection of the broader target cell
specificity of this virus. The low transcriptional activity of
papillomaviruses most likely reflects the low gene expression required
during most or even all parts of the life-cycle of these viruses.

===================================================================
26.) Low frequency of human papillomavirus infection in initial papillary
bladder tumors. (CANADA)
===================================================================
Urol Res 1999 Jun;27(3):180-4

Simoneau M, LaRue H, Fradet Y
Centre de recherche en cancerologie de l'Universite Laval, Centre
Hospitalier Universitaire de Quebec, Canada.

The involvement of human papillomavirus (HPV) in bladder cancer remains
controversial. We previously reported detection of L1-HPV DNA in 39% of
bladder cancers of mixed grade and stage. To clarify the possible etiologic
role of HPV we studied, using the same technique, a more homogeneous group
of initial low-stage tumors. We investigated a total of 187 newly diagnosed
superficial papillary bladder tumors for the presence of L1-HPV DNA by the
polymerase chain reaction method and hybridization with specific probes for
HPV 6, 11, 16, 18, 33. HPV DNA was detected in 16 (8.5%) of the 187
specimens tested, although in a low copy number compared with SiHa cervical
cancer cells used as control. HPV type 16 was observed in eight tumors
while HPV type 6 and type 11 were each observed in three tumors. Two tumor
specimens contained two types of HPV: one tumor hybridized with type 6 and
16 and the other with type 11 and 18. This low rate of HPV detection (8.5%)
in initial tumors does not favor a prominent role for HPV in bladder
carcinogenesis.

===================================================================
27.) Human papillomavirus genotype spectrum in Czech women: correlation of
HPV DNA presence with antibodies against HPV-16, 18, and 33 virus-like
particles. (CZECH REPUBLIC)
===================================================================
J Med Virol 1999 Aug;58(4):378-86

Tachezy R, Hamsikova E, Hajek T, Mikyskova I, Smahel M, Van Ranst M, Kanka
J, Havrankova A, Rob L, Guttner V, Slavik V, Anton M, Kratochvil B,
Kotrsova L, Vonka V
Department of Experimental Virology, Institute of Hematology and Blood
Transfusion, Prague, Czech Republic. rutach@uhkt.cz

Because the biological spectrum of human papillomavirus (HPV) genotypes
present in cervical cancer lesions varies according to the geographical
region studied, and because little genotype information is available for
Central and Eastern European countries, we studied the endemic HPV-genotype
spectrum in cervical samples collected from women visiting gynaecological
departments of selected hospitals in the Czech Republic. In a series of 389
samples, 171 (44.0%) were positive for HPV DNA using a consensus-primer
polymerase chain reaction (PCR). Genotyping of the HPV PCR products was
done using dot-blot hybridisation with type-specific oligonucleotide probes
and thermocycle DNA sequencing. Twenty-two different HPV types were
detected, HPV-16 being the most prevalent type irrespective of severity of
the lesions (55.0%). Multiple HPV types were found in 16.4% of our
HPV-DNA-positive samples. The prevalence of HPV infection was 23.0% in
women with normal findings and 59.4% in patients with cervical neoplasia,
and increased significantly with the severity of the disease: 52.9% in
low-grade lesions, 58.0% in high-grade lesions, and 73.5% in cervical
carcinomas (P for trend < .00001). In the sera of 191 subjects, 89 with
normal findings and 102 with different forms of cervical neoplasia, the
prevalence of HPV-specific IgG antibodies was tested by an enzyme-linked
immunosorbent assay (ELISA) using virus-like particles (VLPs) of HPV-16,
-18, and -33. Antibodies were significantly more prevalent in
HPV-DNA-positive than in HPV-DNA-negative women and there was no
association with age. In agreement with the results of HPV genotyping,
antibodies reactive with HPV-16 VLPs were the most frequent and, moreover,
their prevalence increased with the cervical lesion severity. About half of
the subjects with smears in which either HPV-16 or HPV-33 DNA had been
detected possessed antibodies reactive with homotypic VLPs. With
HPV-18-DNA-positive subjects, however, fewer than 25% displayed homotypic
antibodies. In general, subjects older than 30 years of age had antibodies
reactive to HPV-specific VLPs more often than subjects younger than 30
years of age. In women with benign findings, the seropositivity to HPV-16,
-18, and -33 VLPs increased with age, whereas in women with cervical
neoplasia the seropositivity decreased with age.

===================================================================
28.) Mucosal oncogenic human papillomaviruses and extragenital Bowen disease. (FRANCE)
===================================================================
Cancer 1999 Jul 15;86(2):282-7

Clavel CE, Huu VP, Durlach AP, Birembaut PL, Bernard PM, Derancourt CG
Department of Pathology, Laboratoire Pol Bouin, Cell Biology Unit, CHU de
Reims, France.

BACKGROUND: Genital Bowen disease is known to have a strong association
with human papillomavirus (HPV) type 16. On the other hand, previous
studies of extragenital Bowen disease (EBD) that have used different
hybridization techniques have produced discordant results in the detection
of mucosal oncogenic HPV. METHODS: Ninety-four samples of EBD from 78
patients were investigated clinicopathologically. DNA extracted from fixed
and embedded tissues was analyzed for the presence of the main mucosal
oncogenic HPV types 16, 18, 31, and 33 using polymerase chain reaction
(PCR) with specific primers described in 1996 by Baay et al., which are
particularly well adapted to fixed tissues and give small amplimers.
Moreover, 11 EBD of the hands were investigated by in situ hybridization
(ISH). RESULTS: Of the 94 extragenital BD obtained from 78 patients, HPV
DNA type 16 was detected in 78 cases (83%) from 65 patients (83.3%) by PCR.
Nine patients with EBD of the hands (90%) had HPV type 16, and ISH
displayed a diffuse hybridization pattern that corresponded to the episomal
viral form of HPV DNA. CONCLUSIONS: The current retrospective study of 94
samples clearly demonstrates the high prevalence of HPV type 16 infection
in EBD, especially in EBD of the hands. In this study, no specific
clinical, topographic, or histopathologic features of any lesions were
found to be indicative of the presence or absence of HPV.

===================================================================
29.) High prevalence of a variety of epidermodysplasia
verruciformis-associated human papillomaviruses in psoriatic skin of
patients treated or not treated with PUVA. (GERMANY)
===================================================================
J Invest Dermatol 1999 Jul;113(1):122-6

Weissenborn SJ, Hopfl R, Weber F, Smola H, Pfister HJ, Fuchs PG
Institut for Virology, University of Cologne, Germany.

Epidermodysplasia verruciformis-associated human papillomaviruses and in
particular human papillomavirus type 5 were recently shown to be highly
prevalent in psoriatic skin. We have analyzed lesional skin from 54
psoriasis patients for infections with genital-specific and
epidermodysplasia verruciformis-specific human papillomaviruses to define
the spectrum of involved human papillomavirus types and to test if it is
influenced by psoralen ultraviolet A therapy. Using polymerase chain
reaction analysis we could detect human papillomavirus sequences in skin
lesions of 83% of the tested patients. In contrast, human
papillomavirus-DNA was only demonstrated in 19% of skin samples from 42
dermatologically healthy, immunocompetent individuals. Sequence analysis of
the polymerase chain reaction amplimers revealed 14 human papillomavirus
types, all belonging to the epidermodysplasia verruciformis or
epidermodysplasia verruciformis-related papillomaviruses. Only in one case
we identified sequences related to those of genital viruses, which,
however, represented a putatively new human papillomavirus type. The most
prevalent human papillomavirus type in our patient series was human
papillomavirus type 36, found in 62% of the patients positive for human
papillomavirus-DNA, followed by human papillomavirus type 5 (38%) and human
papillomavirus type 38 (24%). Multiple infections with two to five
different human papillomavirus types could be detected in skin samples of
63% of the analyzed patients. The overall human papillomavirus detection
rate did not differ significantly between patients which have been
subjected to psoralen ultraviolet A photochemotherapy or solely treated
with topical preparations (77 vs 89%). Human papillomavirus type 5,
however, could be detected significantly more frequent in lesions of
psoralen ultraviolet A-treated patients (p < 0.001). Our data strongly
argue for infections with epidermodysplasia verruciformis-specific
papillomaviruses being an almost consistent feature of the lesional
psoriatic skin and substantiate the importance of further studies to
elucidate a possible involvement of human papillomaviruses in psoriasis
pathology.

===================================================================
30.) Human papillomavirus type 31 oncoproteins E6 and E7 are required for
the maintenance of episomes during the viral life cycle in normal human
keratinocytes. (USA)
===================================================================
Proc Natl Acad Sci U S A 1999 Jul 20;96(15):8449-54

Thomas JT, Hubert WG, Ruesch MN, Laimins LA
Department of Microbiology-Immunology, Northwestern University Medical
School, 303 East Chicago Avenue, Chicago, IL 60611, USA.

The E6 and E7 oncoproteins of the high-risk human papillomavirus (HPV)
types are able to immortalize human keratinocytes in vitro and likely
contribute to the development of anogenital malignancies in vivo. The role
of these oncoproteins in the productive viral life cycle, however, is not
known. To begin to examine these possible roles, mutations in E6 were
introduced in the context of the complete HPV 31 genome. Although
transfected wild-type HPV 31 genomes, as well as genomes containing an E6
translation termination linker, an E6 frameshift mutation, and a point
mutation in the p53 interacting domain were able to replicate in transient
assays, only the wild-type genome was stably maintained as an episome.
Interestingly, mutant genomes in either the E6 splice-donor site or
splice-acceptor site were reduced in replication ability in transient
assays; however, cotransfection of E1 and E2 expression vectors restored
this function. In a similar fashion, genomes containing mutant HPV 31 E7
genes, including a translation termination mutant, two Rb-binding site
mutants, a casein kinase II phosphorylation site mutant, and a
transformation deficient mutant, were constructed. Although transient
replication was similar to wild type in all of the E7 mutants, only the
casein kinase II mutant had the ability to maintain high copies of episomal
genomes. These findings suggest a role for E6 and E7 in the viral life
cycle beyond their ability to extend the life span of infected cells.


===================================================================
31.) Clinical, histopathologic, and molecular aspects of cutaneous human
papillomavirus infections. (USA)
===================================================================
Dermatol Clin 1999 Jul;17(3):521-36, viii

Fazel N, Wilczynski S, Lowe L, Su LD
Department of Pathology and Dermatology, University of Michigan School of
Medicine, Ann Arbor, USA.

Human papillomaviruses comprise a large family of double stranded DNA
viruses that are the etiologic agents of benign warts and anogenital
cancers. At least 82 different human papillomavirus types have been
identified and many remain yet uncharacterized. The development of new
molecular techniques in recent years has led to an increased understanding
of human papillomaviruses and their roles in carcinogenesis. Several
clinicopathologic entities arising from human papillomavirus infection
encountered by the dermatologist are the subject of the article. The
epidemiology, molecular biology, clinical presentation, histologic
findings, and treatment of each disorder, where applicable, is discussed.

===================================================================
32.) Screening for genital human papillomavirus: results from an
international validation study on human papillomavirus sampling techniques. (SPAIN)
===================================================================
Diagn Mol Pathol 1999 Mar;8(1):26-31

de Sanjose S, Bosch XF, Munoz N, Chichareon S, Ngelangel C, Balaguero L,
Jacobs MV, Meijer CJ, Walboomers JM
Servei d'Epidemiologia i Registre del Cancer, Institut Catala d'Oncologia,
Barcelona, Spain.

The objective of this study was to determine the validity of human
papillomavirus (HPV) detection using exfoliated cervical cells compared
with cervical biopsy specimens in women with normal cervix and to assess
whether HPV detection rates using exfoliated cells is dependent on the
number and order in which cervical scrapes are taken. Women undergoing
hysterectomy for reasons other than cervical cancer were recruited in three
hospitals in countries with varying risks of cervical cancer. After
informed consent and at the time of surgery, three consecutive cervical
scrapes were taken as well as four biopsy specimens, one in each of the
quadrants around the cervical os. In this study, 331 women were recruited
and provided 992 cell samples and 1324 biopsy samples. All scrapes and a
sample of biopsy specimens (n = 103) were tested by polymerase chain
reaction enzyme immunoassay using a general primer (GP5+/ bio6+).
Type-specific tests were performed for 14 HPV types at the subpicogram
level in one test and individually. Positive samples were verified using
Southern blot hybridization. The prevalence of HPV DNA was 6.3% in cervical
cells. Of 19 HPV positive samples in the scrapes, 17 were confirmed in the
biopsy specimens. The agreement, as measured by the Kappa statistic, was
0.90 (P < 0.0001). The concordance in detecting HPV infection between
scrapes and biopsy specimens was 97.5%, and the concordance in categorizing
the samples as negatives was 94.4%. These values were unchanged when the
order in which scrapes were taken was compared. Among women without
cervical cancer, HPV DNA detection rates do not vary if exfoliated cells or
random biopsy specimens are taken as the primary testing specimen.
Screening programs based on highly sensitive HPV DNA detection technology
in cell scrapes should expect a minimal underdetection.

===================================================================
33.) Use of the same archival papanicolanou smears for detection of human
papillomavirus by cytology and polymerase chain reaction. (AUSTRALIA)
===================================================================
Diagn Mol Pathol 1999 Mar;8(1):20-5

McDonald RL, Rose BR, Gibbins J, Baird PJ
Cytology Department, Baird Pathology, Toongabbie, New South Wales, Australia.

An optimal method for the processing of archival cervical Papanicolaou
(pap)-stained smears for the amplification of human papillomavirus (HPV)
DNA by polymerase chain reaction (PCR) was developed. This methodology was
then applied to a series of 44 pap smears designated as HPV positive or
negative (on the basis of both major and minor cytological criteria) or
cervical intraepithelial neoplasia (CIN)-cancer. For the detection of HPV
DNA, each sample was tested with the consensus GP5/6 primers, and when
negative, with CPI-IIG primers. The HPV DNA was detected in 100% (8 of 8)
of CIN-cancer smears using the GP5/6 primers. In smears with cytological
evidence of HPV without CIN. the use of both sets of primers yielded
positive results in 100% (19 of 19) of the samples. Direct sequence
analysis of PCR products showed that 16 of the 27 HPV-positive samples
contained more recently described HPV types. When tested with both primer
combinations, all 17 cytologically negative smears were positive for
beta-globin but negative for HPV DNA. The findings show the value of using
archival pap smears for further investigations to address issues such as
latency, but they indicate that cytological criteria and DNA technology
will be critical factors in the reliability of the results.

===================================================================
34.) Detection and typing of human papillomavirus in cervical cancer in the
Thai. (THAILAND)
===================================================================
J Med Assoc Thai 1996 Dec;79 Suppl 1:S56-64

Bhattarakosol P, Poonnaniti A, Niruthisard S
Department of Microbiology, Faculty of Medicine, Chulalongkorn University,
Bangkok, Thailand.

One hundred formalin-fixed paraffin embedded tissues with histopathologic
diagnosed invasive cervical cancer (squamous cell carcinoma) were examined
for the presence of HPV-DNA by polymerase chain reaction (PCR) using
L1-consensus primers. The results indicated that 82 out of 100 (82%)
samples were positive for HPV-DNA. Among the positive samples, 50 samples
(61%) were typed by dot hybridization technique (DH). HPV-16 was the
dominant type (42.68%), followed by HPV-18 (20.73%) and HPV-33 (3.66%).
There were double infection of HPV-16 and 18 in 5 (6.1%) samples. None of
HPV-6 and 11 were detected in this study. This finding suggests that HPV
infection is an important etiologic factor for the development of cervical
cancer especially the infection with high risk types, i.e., HPV-16 and 18.

===================================================================
35.) Correlation between polymerase chain reaction and cervical cytology
for detection of human papillomavirus infection in women with and without
dysplasia. (NORWAY)
===================================================================
APMIS 1997 Jan;105(1):71-5

Gjoen K, Sauer T, Olsen AO, Orstavik I
Department of Virology, National Institute of Public Health, Oslo, Norway.

The aim of this study was to compare the ability of two methods, the
polymerase chain reaction (PCR) and cervical cytology, to detect HPV
infection. The study population included 222 randomly selected women
without dysplasia (controls) and 91 women with histologically confirmed
dysplasia (CIN II-III) (cases). In women without dysplasia, 8.6% had
cytological signs of HPV infection, whereas 15.3% were HPV DNA positive by
PCR. In women with dysplasia, 72.5% had cytological signs of HPV infection,
whereas 90.1% were HPV PCR positive. The statistical agreement between the
two diagnostic methods was low (controls: kappa = 0.26, cases: kappa =
-0.03). In total, PCR failed to detect 17 of 85 women with cytological
signs of HPV infection, whereas cervical cytology failed to detect 48 of
116 HPV PCR-positive women. In women with dysplasia, but not in women
without dysplasia, the oncogenic HPV types were associated with cytological
signs of HPV infection.

===================================================================
36.) Detection and quantitation of human papillomavirus by using the
fluorescent 5' exonuclease assay. (SWEDEN)
===================================================================
J Clin Microbiol 1999 Mar;37(3):490-6

Josefsson A, Livak K, Gyllensten U
Department of Genetics and Pathology, Unit of Medical Genetics, University
of Uppsala, S-751 23 Uppsala, Sweden.

A method for the detection and quantitation of oncogenic human
papillomavirus (HPV) was developed by using the fluorescent 5' exonuclease
assay. The method is based on the amplification of a 180-bp fragment from
the 3' part of the E1 open reading frame in a single PCR with type-specific
probes for HPV types 16, 18, 31, 33, and 35. The probes can be used
separately or in combinations of up to three probes per assay. Quantitation
over a range of 10(1) to 10(6) initial HPV copies was possible by using
real-time detection of the accumulation of fluorescence with cycle number.
Reconstitution experiments, performed to mimic mixed infections, showed
that individual HPV types can be detected down to a ratio of about 1% in a
mixture. The performance of the assay depends on DNA quality, the presence
of PCR inhibitors, and the number of different probes used simultaneously.
This homogeneous assay provides a fast and sensitive way of screening for
oncogenic HPV types in biopsy specimens as well as cervical smear samples.
The closed-tube nature of the assay and the inclusion of uracil
N'-glycosylase reduces cross contamination of PCR products to a minimum. A
similar assay for beta-actin was used in parallel for quantitation of
genomic DNA. After normalizing the samples for genomic DNA content, the
mean number of HPV copies per cell could be calculated.

===================================================================
37.) Risk factors for HPV detection in archival Pap smears. A
population-based study from Greenland and Denmark. (GREENLAND AND DENMARK)
===================================================================
Eur J Cancer 1998 Jul;34(8):1230-4

Svare EI, Kjaer SK, Smits HL, Poll P, Tjong-A-Hung SP, ter Schegget J
Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen, Denmark.

The most important risk factor for cervical cancer is genital infection
with certain types of human papillomavirus (HPV). The presence of HPV was
studied in archival smears from a random sample of women living in
Greenland (GW) and Denmark (DW) having, respectively, a high risk and an
intermediate risk for cervical cancer. Risk factors were also examined of
the original 126 Danish and 129 Greenlandic archived smears collected
during October and November 1988. 125 were located from each country
including all abnormal smears. HPV DNA was isolated from the smears and
detected by means of a consensus polymerase chain reaction (PCR) detecting
a broad spectrum of genital HPV types. HPV was detected in all the abnormal
smears and in 22 and 33% respectively of the cytological normal smears from
DW and GW. Risk of HPV was significantly higher in smears from women who
started sexual life relatively recently (respectively, < or = 4 and < or =
6 years ago in DW and GW) compared with > or = 10 years ago (adjusted
prevalence-OR: 9.3; 95% CI: 2.2-39.2 in DW and 5.9; 95% CI: 1.4-25.3 in
GW). Among other important risk factors were age in both areas, lifetime
number of sex partners and current smoking in DW and ever and gonorrhoea in
GW. This study confirms the usefulness of the method as all abnormal smears
were positive and, furthermore, the predictors for HPV presence in the
normal smears corroborate with those found in recent studies of HPV in
fresh cervical swabs. Thus, this method can be useful for large-scale
epidemiological studies of HPV DNA in already sampled material.

===================================================================
38.) [Human papillomavirus infection in women with and without abnormal
cervical cytology]. (MEXICO)
===================================================================
Ginecol Obstet Mex 1993 Feb;61:27-34

Tamayo Legorreta EM, Echaniz Aviles G, Cruz Valdez A, Camacho Alcantara G,
Calderon Jaimes E
Centro de Investigaciones sobre Enfermedades Infecciosas, Instituto
Nacional de Salud Publica, Cuernavaca, Mor.

This study sought to define the prevalence rates of human papillomavirus
(HPV) infection and cytologic abnormalities in 3,257 sexually active
females 13 to 45 years of age, undergoing routine cervical cytologic
screening in the outpatient clinic of an urban hospital. One hundred and
fifty patients (4.6%) showed cytologic evidence of cervical human
papillomavirus infection (abnormal Pap). We selected a control group (n =
150) with negative cervical cytologic smears. Cells collected were analysed
for HPV-DNA by PCR amplification method with probes for HPV types 6.11,
16.18 and 33. The HPV-DNA was detected in 21/300 (7.0%). The prevalence of
cervical HPV-DNA types among women with negative cytology was 5.3% (8/150)
and 8.6% (13/150) among women with abnormal Pap. The risk of HPV infection
seems to be related with age at first intercourse, younger age and number
of sexual partners. We did not find relation with the use of oral
contraceptives smoking and history of prior sexually transmitted disease.

===================================================================
39.) Follow-up of human papillomavirus (HPV) DNA and local anti-HPV antibodies in cytologically normal pregnant women. (HUNGARY)
===================================================================
Med Microbiol Immunol (Berl) 1996 Nov;185(3):139-44

Veress G, Csiky-Meszaros T, Konya J, Czegledy J, Gergely L
Department of Microbiology, University Medical School of Debrecen, Hungary.

The high level of progesterone during pregnancy may enhance the
transcription and replication of genital human papillomaviruses (HPV)
through the glucocorticoid/progesterone response element found in the long
control region of the viral genome. In this study, cytologically and
colposcopically healthy pregnant women were subjected to a follow-up
examination. Samples from the uterine cervix were collected during early
pregnancy (n = 39), in the third trimester (n = 31), and a few weeks after
birth (n = 30). The presence of HPV DNA was detected by polymerase chain
reaction (PCR), while local secretory anti-viral IgA antibodies were
demonstrated by enzyme-linked immunosorbent assay using synthetic peptide
antigens. Follow-up examination by PCR revealed HPV DNA persistence in 5
women. In 5 other cases, HPV positivity changed from negative to positive
during the follow-up. There was 1 case which changed from positive to
negative and 1 in which the HPV type changed during the study. Altogether,
12 of 39 women (31%) were shown to harbor HPV DNA at some time during
follow-up. HPV DNA positivity increased from 18% during early pregnancy to
27% after birth (difference not significant). On the other hand, there was
a significant rise in the level of local antibodies against HPV antigens
(E2, E7, and L2) between samples collected in early pregnancy and those
collected after birth (P < 0.0001). This may indicate the reactivation of
genital HPV infections during late pregnancy.

===================================================================
40.) Relatively low prevalence of human papillomavirus 16, 18 and 33 DNA in
the normal cervices of Japanese women shown by polymerase chain reaction. (JAPAN)
===================================================================
Jpn J Cancer Res 1991 May;82(5):532-8

Nishikawa A, Fukushima M, Shimada M, Yamakawa Y, Shimano S, Kato I, Fujinaga K
Department of Obstetrics and Gynecology, Cancer Research Institute, Sapporo
Medical College.

Ninety-two cervical scrapes and tissues, obtained from cytologically or
histologically normal cervices of Japanese women, were examined for the
presence of human papillomavirus (HPV) 16, 18 and 33 DNA by the polymerase
chain reaction (PCR) method. Five out of 92 cases were HPV 16 DNA-positive,
but neither HPV 18 nor 33 DNA was detected. The HPV (type 16, 18 and 33)
prevalence rate in pregnant women, including postpartum, was 10% (3/31),
which was higher than that in non-pregnant women. In two HPV 16-positive
cases, we detected HPV 16 DNA again 2 months later. HPV (type 16, 18 and
33) prevalence in normal cervices was shown to be relatively low. However,
it is very important to follow up the HPV-positive cases in cytologically
normal cervices in order to elucidate the relation between HPV infection
and the progression of cervical cancer.

===================================================================
41.) Comparison of a one-step and a two-step polymerase chain reaction with
degenerate general primers in a population-based study of human papillomavirus infection in young Swedish women. (SWEDEN)
===================================================================
J Clin Microbiol 1992 Apr;30(4):987-92

Evander M, Edlund K, Boden E, Gustafsson A, Jonsson M, Karlsson R, Rylander
E, Wadell G
Department of Virology, University of Umea, Sweden.

The prevalence of human papillomavirus (HPV) infection in cervical cell
scrapes from young women was determined by polymerase chain reaction (PCR)
by using general primer pairs localized within the L1 region. With a
one-step general PCR, 5.9% (35 of 590) of young women in a population-based
study were found to contain HPV DNA. The proportion of HPV-positive women
increased with age, from 1.4% (1 of 69) among women aged 19 years to 9.2%
(13 of 142) among women aged 25 years. Among the cervical scrapes from
women with normal cytology, 5.6% (30 of 539) harbored HPV DNA. A total of 5
of 19 (26.3%) of the women with pathological signs were positive for HPV
DNA. By a two-step PCR, using nested general primers, 20.3% (118 of 581) of
all women were shown to contain HPV DNA. The proportion of HPV-positive
women also increased with age, from 17.4% (12 of 69) among women aged 19
years to 31.9% (43 of 135) among women aged 25 years, when the two-step PCR
was used. Some 19.2% (102 of 530) of cervical scrapes from women with
normal cytology contained HPV DNA. Among the women with pathological signs,
16 of 19 (84.2%) were positive for HPV DNA. The HPV DNA-positive specimens
were demonstrated to contain HPV type 6, 11, 16, 18, 31, 33, 35, 39, 40,
45, 55, or 56. The most prevalent HPV types were 6 (2.0%) and 16 (2.7%).
More than one type was found in 16 specimens. Sixty HPV-positive samples
could not be typed.

===================================================================
42.) Human papillomavirus DNA in unselected pregnant and non-pregnant women. (FINLAND)
===================================================================
Int J STD AIDS 1990 Jul;1(4):276-8

Soares VR, Nieminen P, Aho M, Vesterinen E, Vaheri A, Paavonen J
Department of Obstetrics and Gynecology, University Central Hospital,
Helsinki, Finland.

Human papillomavirus (HPV) DNA is associated with genital squamous cell
neoplasia, especially types 16, 18, and 31. Several studies, using
histopathology and DNA hybridization, have shown an increased prevalence of
cervical HPV DNA in pregnant women. We determined the prevalence of HPV DNA
and the distribution of specific HPV DNA types in exfoliated cervical cells
from 748 randomly selected pregnant and 503 non-pregnant women, using a dot
blot DNA hybridization technique. The prevalence of HPV DNA was 9.6% in
pregnant women and 8.9% in non-pregnant women. Thus, we found no evidence
of higher prevalence of HPV DNA in pregnant women. HPV DNA types 16/18 and
31/33/35 were more common than types 6/11. The prevalence of HPV DNA was
highest (15%) in the youngest age groups suggesting an association between
young age and the prevalence of HPV DNA.

===================================================================
43.) Prevalence of HPV cervical infection in a family planning clinic determined by polymerase chain reaction and dot blot hybridisation. (LONDON)
===================================================================
J Med Virol 1991 Jul;34(3):154-8

Hallam N, Green J, Gibson P, Powis J, Bibby J
Virus Reference Laboratory, Central Public Health Laboratory, London.

The overall prevalence of human papillomavirus (HPV) cervical infection in
131 women attending a family planning clinic was 7% (HPV 6/11, 16, 18, 31)
by dot blot hybridisation, 53% (HPV 11, 16, 31) by polymerase chain
reaction (PCR), and 56% by the two methods combined. HPV 16 and 18 were the
commonest types (4% each) by dot blot, HPV 16 (39%) by PCR. Fifteen percent
of subjects had mildly abnormal cervical cytology (grades 1A, 2A, or 3).
There was no significant correlation between cytological abnormality and
HPV positivity, or between cytological or HPV status and other postulated
risk factors for cervical neoplasia. It is concluded that PCR is
considerably more sensitive than dot blot DNA hybridisation in detecting
HPV cervical infection in such a "low risk" setting, where HPV copy number
may be low. Firm conclusions cannot be drawn from our results regarding a
causal role for HPV or other factors in the development of cervical
neoplasia.

===================================================================
44.) Type-specific prevalence of human papillomavirus DNA among Jamaican colposcopy patients. (JAMAICA)
===================================================================
J Infect Dis 1996 Mar;173(3):718-21

Rattray C, Strickler HD, Escoffery C, Cranston B, Brown C, Manns A,
Schiffman MH, Palefsky JM, Hanchard B, Blattner WA
Department of Obsterics/Gynecology, University Hospital of the West Indies,
Kingston, Jamaica.

Human papillomavirus (HPV) types differ in their association with cervical
cancer. Therefore, the types of HPV in precancerous lesions are important.
In many regions with high cancer incidence, the HPV types in precancerous
lesions have not been well studied. In Jamaica, a country that has high
cervical cancer incidence, 174 colposcopy patients were tested for HPV DNA
using polymerase chain reaction. HPV DNA detection was strongly related to
presence and grade of cervical neoplasia (P<.001). Furthermore, severe
neoplastic change was most highly associated with HPV DNA types also
considered high-risk for severe neoplasia in other populations. HPV-45 DNA,
a high-risk type uncommon in most previously tested countries, was detected
in 12% of patients who had neoplasia. Thus, cervical neoplasia in Jamaica,
as elsewhere, is linked to HPV. The high prevalence of HPV-45 was notable,
and its relation to high cervical cancer incidence in Jamaica must be
assessed.

===================================================================
45.) Polymerase chain reaction detection and restriction enzyme typing of human papillomavirus in cervical carcinoma. (MALAYA)
===================================================================
Med J Malaysia 1995 Mar;50(1):64-71

Yadav M, Nurhayati ZA, Padmanathan A, Abdul Aziz Y, Norhanom AW
Department of Genetics & Cellular Biology, University of Malaya, Kuala
Lumpur.

Specific human papillomavirus (HPV) types have been implicated in the
development of cervical carcinoma worldwide. Novel molecular techniques
have facilitated the detection and typing of HPV in cervical lesions. DNA
preparations from a series of 23 histopathologically confirmed cervical
carcinoma patients were analyzed by polymerase chain reaction (PCR) using
degenerate primers for the presence of HPV DNA sequences. A total of 22 of
23 cases studied (95.7%) were found positive for HPV DNA sequences. Further
studies by DNA hybridization with viral specific probe and restriction
enzyme analysis demonstrated the presence of HPV 16 in 73.9% (17/23) and
HPV 18 in 65.2% (15/23) of the cases examined. Interestingly, the uncommon
HPV 31 and 33 were also found but with a lower percentage (16.9%). It was
noted that HPV 16 frequency in the carcinoma increased with age but HPV 18
was evenly present at all ages investigated. We found that HPV was
frequently associated with the majority of the cervical carcinomas, and in
all but one case, oncogenic high risk HPV genotypes were present. We
conclude that HPV infection of the genital tract has an important role in
the development of the disease in Malaysia.

===================================================================
46.) Human papillomavirus (HPV) cervical lesions: results from 300 Italian
women studied with DNA hybridization techniques and morphology. (ITALY)
===================================================================
Tumori 1988 Dec 31;74(6):745-9

Nuzzo F, Tison V, Castagnoli A, Tiboni M, De Villiers EM
Dipartimento di Patologia, Osp. M. Bufalini, Cesena, Italia.

Human papillomavirus cervical infection was investigated in a series of 300
unselected women by comparing morphological diagnoses (cytology and
histology) with results of DNA hybridization techniques (filter in situ
hybridization of DNA from exfoliated cervical cells and Southern blot
analysis of HPV-DNA in cervical biopsy specimens). The prevalence of HPV
cervical infection diagnosed by PAP smears was 11.6%. Despite
disadvantages, filter in situ hybridization was confirmed to be
particularly useful for screening purposes to detect HPV in cervical
scrapings. In 3 cases it was the only applicable method for diagnosing
"high-risk" HPV infection. Southern blot hybridization of tissue DNA with
HPV 16-DNA revealed the presence of this virus in 8 cases, and HPV 31-DNA
and HPV 42-DNA in 1 case each.

===================================================================
47.) Detection of human papillomavirus (HPV) DNA in human prostatic tissues by polymerase chain reaction (PCR). (USA)
===================================================================
Prostate 1993;22(2):171-80

Sarkar FH, Sakr WA, Li YW, Sreepathi P, Crissman JD
Department of Pathology, Wayne State University School of Medicine,
Detroit, Michigan 48201.

Human papillomavirus (HPV) infections are strongly linked to the
pathogenesis of uterine cervical neoplasms, and have been implicated in
other cancers of the female genital tract. In contrast, the association of
HPV with the cancers of the male urogenital tract is less evident, except
in anal and penile cancers. However, recent studies reporting the
prevalence of HPV infections in human prostate cancers (60-100% HPV 16
positive vs. no infection of HPV) have raised controversies regarding the
prevalence of HPV in benign and neoplastic human prostate. We investigated
the prevalence of HPV infections in prostatic intraepithelial neoplasia
(PIN) and prostatic adenocarcinomas in 23 surgically resected prostates.
Polymerase chain reaction (PCR) was used to amplify HPV 6b/11, 16, and 18
specific DNA sequences, using type specific HPV primers selected from the
transforming gene E6-E7. The areas of PIN and cancer in 6 microns H&E
stained tissue sections were identified, and respective areas of PIN and
cancer were isolated from the adjacent serial sections and used for DNA
amplification and HPV detection (Fig. 1). Our results demonstrated the
presence of HPV 16 in three carcinomas (13%), using type specific primers
in PCR amplified samples. We were not able to demonstrate the presence of
other HPV types (HPV 6b/11 or HPV 18) in any of the samples using specific
primers. Two of these prostates showed relatively strong positive signals
by dot blot analysis, when hybridized with a 32P-labeled HPV 16 type
specific oligonucleotide probe. One more sample showed weak positivity,
when hybridized with a 32P-labeled HPV 16 type specific oligonucleotide
probe. Subsequently, we have confirmed these results by Southern
hybridization of the samples transferred to nylon membrane after agarose
gel electrophoresis and detected by HPV 16 type specific oligonucleotide
probe, using chemiluminescent assay. We, therefore, conclude that HPV
infections of the prostate in general are not as common as has been
previously claimed by other investigators.

===================================================================
48.) High-risk human papillomavirus types in cytologically normal cervical scrapes from Kenya. (KENYA)
===================================================================
Med Microbiol Immunol (Berl) 1992;180(6):321-6

Czegledy J, Rogo KO, Evander M, Wadell G
Institute of Microbiology, University Medical School of Debrecen, Hungary.

Seventy-seven women with normal cervical cytology on routine visit to a
family planning clinic in Nairobi, Kenya, were analysed for genital human
papillomavirus (HPV) types by polymerase chain reaction (PCR). We applied a
general primer pair (GP60/GP124) recognising sequences conserved among HPV
types 6, 11, 16, 18, 31 and 33. Of the 77 specimens tested 15 (19.5%)
proved to be positive for genital HPV. Amplification products were examined
for the presence of high-risk HPV types by Slot-blot hybridization. Out of
the 15 PCR-positive samples, 4 were positive for HPV 16.3 for HPV 18, while
1 contained both HPV 16 and 33. HPV DNA prevalence in this group of women
from a "high-risk" area is similar to that in "low-risk" Swedish women but
much lower than in cervical cancer samples from the same region.

===================================================================
49.) Detection of type specific human papillomavirus (HPV) DNA in cervical cancers of Indian women. (INDIA)
===================================================================
Indian J Pathol Microbiol 1995 Jan;38(1):33-42

Chatterjee R, Roy A, Basu S
Department of Tumor Virology, Chittaranjan National Cancer Institute,
Calcutta, India.

Commercial Vira Pap and Vira Type kits of Life Technologies Inc., U.S.A.,
were used to determine prevalence and type specific distribution of human
papilloma viruses (HPV) in 18 biopsy samples of cervical carcinomas and 26
specimens of exfoliated cervical cells (swabs). The women were either
attending out-patient's department of a suburban hospital or a cancer
hospital in Calcutta, India. HPV DNA was detected in 9 biopsy specimens but
not in any of the cervical swabs. Five of the 9 HPV positive biopsies had
HPV DNA type 16/18. Neither HPV 6/11 nor HPV 31/33/35 DNAs were detected in
any of these 9 specimens. Results indicated possible presence of HPV DNAs
of types other than the above in at least 4 specimens.

===================================================================
50.) Natural history of cervical human papillomavirus lesions. (JAPAN)
===================================================================
Intervirology 1995;38(3-4):192-4

Katase K, Teshima H, Hirai Y, Hasumi K
Department of Gynecology, Cancer Institute Hospital, Tokyo, Japan.

A total of 87 HPV-positive patients with grade I and II cervical
intraepithelial neoplasia (CIN I and II) were followed up by cytology and
colposcopy every 3 months for more than 5 years following the first biopsy.
These patients were classified into three groups (progressive, persistent,
and regressive disease) according to the results. The human papillomavirus
(HPV) genome and viral types were identified by Southern blot hybridization
at Tm-40 degrees and Tm-20 degrees with DNA extracted from exfoliated
cervical cells. The lesion progressed to CIN III in 4/87 patients (4.6%),
persisted in 39 patients (44.8%), and regressed in 44 patients (50.6%). In
the progressive disease group, HPV 16 was detected in 2 patients, HPV 33 in
1 patient, and HPV 52 in 1 patient. In the persistent disease group, HPV 58
was predominant (28%), whereas in the regressive disease group, there was
no predominant HPV type. In 10/39 patients from the persistent disease
group, cytological examination transiently revealed severe dysplasia and/or
findings similar to carcinoma in situ. These patients showed severe
cytological abnormalities only once or twice during the follow-up. These
results suggest that the natural history of CIN possibly depends upon the
type of HPV that infects the cervix, and the relative risk of progression
was similar to that shown by previous cross-sectional studies.

===================================================================
51.) Detection of human papillomavirus types in cervical lesions of patients from Taiwan by the polymerase chain reaction. (TAIWAN)
===================================================================
Sex Transm Dis 1994 Nov-Dec;21(6):309-14

Wu CH, Lee MF, Chang MC, Ho SC
Department of Medical Research, Taichung Veterans General Hospital, Taiwan,
Republic of China.

BACKGROUND AND OBJECTIVES: The association of human papillomavirus (HPV)
infection with cervical carcinoma is well documented. The HPV types in
cervical lesions of patients from Taiwan are analyzed by the polymerase
chain reaction (PCR). STUDY DESIGN: DNA was extracted from
paraffin-embedded, formalin-fixed tissues using a sonication method. PCR
was performed using type-specific primers for the presence of HPV types 6,
11, 16, 18, 31, and 33 DNA. Amplified product was subjected to gel
electrophoresis and Southern blot hybridization analysis. RESULTS: A total
of 129 cervical lesions and normal cervical biopsies were examined.
Histologic examination revealed a spectrum of lesions, which were
classified as condyloma acuminata (AC), condyloma (CL), koilocytosis (KL),
various grades of cervical intraepithelial neoplasia (CIN I, II, and III),
carcinoma in situ (CIS), and invasive carcinoma (ICa). Of 114 cervical
lesions, 65% (26 of 40) of AC; 61% (11 of 18) of CL; 20% (2 of 10) of KL;
25% (1 of 4) of CIN I; 69% (9 of 13) of CIN II; 80% (12 of 15) of CIN III;
83% (5 of 6) of CIS; and 100% (8 of 8) of ICa were positive for at least
one type of HPV by the PCR. Among the 74 HPV-positive specimens, 19 (26%)
were detected with multiple types. HPV DNA was detected in the cervical
biopsies of 1 of 15 (6.7%) normal individuals. CONCLUSION: Excluding AC,
HPV 6 and/or 11 (HPV 6/11), HPV 16 and/or 18 (HPV 16/18), and HPV 31 and/or
33 (HPV 31/33) were detected in 40% (19 of 48), 71% (34 of 48), and 12% (6
of 48) of neoplastic lesions of patients from Taiwan respectively. These
findings are compatible with those reported by others worldwide.

===================================================================
52.) Human papillomaviruses in cervical cancer I. HPV-16 and 18 predominate in the Greek population. (GREEK)
===================================================================
Anticancer Res 1997 Jan-Feb;17(1A):117-20

Vassilandonopoulou G, Panotopoulou E, Fotiou S, Tserkezoglou A, Machera E,
Kottaridis S
St. Savas Hospital, Papanikolaou Research Center, Athens, Greece.

Human papillomaviruses (HPV) and their role in carcinogenesis have been the
subject of extensive investigation Specific types of HPV have been
associated with cervical carcinoma HPV 16 and 18 are mainly associated with
malignant progression and considered "high risk" viruses Using Southern
blot analysis and in situ hybridization we investigated the presence of
papilloma viruses in cervical carcinoma patients as well as appropriate
controls. The results presented here support the aetiological role of HPV
16 and 18 in cervical carcinoma and demonstrate the prevalence of these
viruses in Greek women. The role of viruses in carcinogenesis in well
established in almost all species from fishes, to birds, to mammals.
Although not well circumstantiated, viruses probably play as-great a role
in human cancer as in other species. The role of human papillomaviruses
(HPV) not only in benign proliferations, but also in a number of
malignancies has long been postulated (1,2). Presently over 20 HPV types
have been identified and there is evidence now associating specific types
with certain human anogenital cancers, notably cervical cancer (3,4).
Advance neoplasias such as squamous cell carcinomas are associated with
types, 16,18 and 31, with type 16 prevailing in these lesions (5,6). In
this paper we shall present evidence which extends and confirms that
previously reported on the prevalence of HPV 16 and 18 in Greek women.

===================================================================
53.) The prevalence of cervical infection with human papillomaviruses and cervical dysplasia in Alaska Native women. (ALASKA)
===================================================================
J Infect Dis 1994 Apr;169(4):792-800

Davidson M, Schnitzer PG, Bulkow LR, Parkinson AJ, Schloss ML, Fitzgerald
MA, Knight JA, Murphy CM, Kiviat NB, Toomey KE, et al
National Center for Infectious Diseases, Centers for Disease Control and
Prevention, Anchorage, Alaska.

Alaska Native women historically have high rates of sexually transmitted
diseases (STDs) and invasive cervical cancer. Their prevalence of cervical
infections with human papillomavirus (HPV) in relation to cervical
dysplasia was determined with a commercial dot hybridization test for seven
HPV genotypes. Type-specific HPV DNA, similarly distributed between
genotype groups 16/18 and 31/33/35, was detected in 234 cervical specimens
(21%) from 1126 Alaska Native women seeking routine care and colposcopy or
from population-based lists. The prevalence of HPV DNA declined with age
and increased with sexual activity and cigarette smoking. It was unrelated
to use of oral contraceptives or condoms or to STDs. Relative risks
associating HPV with increasing severe grades of cervical dysplasia
increased markedly with HPV infection, up to 7.1 for high-risk genotypes
16/18 and 14.4 for coinfection with 31/33/35. These genotypes were detected
in 8% of women without dysplasia seeking routine care. Screening for
strain-specific HPV DNA may identify women at highest risk for cervical
neoplasia.

===================================================================
54.) Detection of human papillomaviruses in exfoliated cervicovaginal cells by in situ DNA hybridization analysis. (TAIWAN-CHINA)
===================================================================
J Clin Microbiol 1989 Jan;27(1):168-73

Pao CC, Lai CH, Wu SY, Young KC, Chang PL, Soong YK
Department of Biochemistry, Chang Gung Medical College, Taipei, Taiwan,
Republic of China.

A total of 851 specimens of exfoliated cervicovaginal cells and 27
specimens of male urethral smears obtained from 706 individuals with
various clinical findings were examined for the presence of human
papillomavirus (HPV) types 6, 11, 16, 18, 31, and 33 by in situ DNA
hybridization analysis. The nonradioactive DNA in situ hybridization method
used in this study showed no detectable cross-hybridization either among
different types of HPV (except between types 6 and 11) or between HPV DNA
and human cellular DNA. Furthermore, this system was found to be more
sensitive than the Southern blotting method in detecting HPV. HPV was found
in 233 of 276 (84.4%) and in 34 of 47 (72.3%) samples of cervicovaginal
cells from patients with urogenital condylomata and cervical dysplasia,
respectively. HPV was also detected in 6 of 39 (15.4%) women with normal
cytological findings who were also symptom-free. Young women who were at
low risk but were infected with HPV showed significantly reduced ratios of
helper-inducer T lymphocytes to suppressor-cytotoxic T lymphocytes compared
with those of uninfected normal controls (1.28 +/- 0.31 versus 2.47 +/-
0.64; P less than 0.001). This in situ DNA hybridization method can have
broad application to the screening of HPV in early lesions and in
normal-looking tissues and may be used to identify patients at risk of more
serious or possibly malignant progression.

===================================================================
55.) Detection and typing of human papillomavirus in cervical specimens of Turkish women. (TURKEY)
===================================================================
Eur J Gynaecol Oncol 1997;18(6):546-50

Guney AI, Ince U, Kullu S, Pekin S, Cirakoglu B
Department of Medical Biology and Genetics, Faculty of Medicine, University
of Marmara, Istanbul, Turkey.

The DNA in situ hybridization (DISH) and conventional solution phase
polymerase chain reaction (PCR) were applied to identify human
papillomavirus (HPV) DNA in cervical specimens of Turkish women. Samples
consisted of 21 cervical brushings from pregnant women and 20
paraffin-embedded biopsies from women with condylomatous or dysplasic
lesions. It was found that two out of 21 (9.5%) pregnant women were
harbouring HPV-DNA detected by PCR. One woman was infected with HPV 16/30's
and the other with an unidentified type. As for the biopsy specimens, the
rate of HPV-DNA positivity was 30% and 45% by DISH and PCR, respectively. A
double infection was observed in more than 50% of the positive cases.
Moreover, HPV 18 was never detected. The results indicated that HPV-DNA is
rarely present in cytomorphologically normal smears from pregnant women.
The PCR method was successfully adapted for HPV typing in clinical lesions
which simultaneously contained different HPV sequences.

===================================================================
56.) Prevalence of human papillomavirus DNA in cervical tissue. Retrospective analysis of 855 cervical biopsies. (GERMANY)
===================================================================
Arch Gynecol Obstet 1997;259(2):69-77

Backe J, Roos T, Mulfinger L, Martius J
Department of Obstetrics and Gynecology, University of Wurzburg, Germany.

The histopathologic features of 855 cervical biopsies were correlated with
the presence of human papillomavirus DNA using in situ hybridization (ISH)
with biotin labeled type specific probes for Human Papilloma Virus (HPV)
types 6, 11, 16, 18, 31, 33 and 51. HPV-DNA was found in 18% (13/72) of
cervical intraepithelial neoplasia I (CIN I), 30% (35/115) of CIN II, 28%
(57(206) of CIN III, in 84% (21/25) of flat condyloma and in 13% (15/112)
of normal cervical tissue. HPV DNA was detectable in 11% (5/46) of cervical
adenocarcinoma and in 21% (59/279) of squamous cell carcinoma (SCC) of the
cervix. High risk HPV types were identified more often than low risk HPV
types in CIN I, CIN II, CIN III and SCC. HPV type 16/18 predominates over
HPV types 31/33/51 in CIN I, flat condyloma and in SCC. The prevalence of
HPV was strongly associated with the grade of differentiation of SCC. It
was identified in 59% (23/39) of well differentiated SCC, in 18% (25/142)
of moderately differentiated and in 11% (11/98) of poorly differentiated SCC.

===================================================================
57.) Prevalence of human papillomavirus DNA in female cervical lesions from Rio de Janeiro, Brazil. (BRAZIL)
===================================================================
Mem Inst Oswaldo Cruz 1994 Oct-Dec;89(4):575-80

Cavalcanti SM, Frugulhetti IC, Passos MR, Fonseca ME, Oliveira LH
Departamento de Microbiologia e Parasitologia, Universidade Federal
Fluminense, Niteroi, RJ, Brasil.

A hundred-sixty paraffin-embedded specimens from female cervical lesions
were examined for human papillomavirus (HPV) types 6, 11, 16 and 18
infections by non-isotopic in situ hybridization. The data were compared
with histologic diagnosis. Eighty-eight (55%) biopsies contained HPV DNA
sequences. In low grade cervical intraepithelial neoplasias (CIN I), HPV
infection was detected in 78.7% of the cases, the benign HPV 6 was the most
prevalent type. HPV DNA was detected in 58% of CIN II and CIN III cases and
in 41.8% of squamous cell carcinomas (SCC). Histologically normal women
presented 20% of HPV infection. Oncogenic HPV was found in 10% of these
cases, what may indicate a higher risk of developing CINs and cancer.
Twenty-five percent of the infected tissues contained mixed infections. HPV
16 was the most common type infecting the cervix and its prevalence raised
significantly with the severity of the lesions, pointing its role in cancer
pathogenesis. White women presented twice the cervical lesions of mulatto
and African origin women, although HPV infection rates were nearly the same
for the three groups (approximately 50%). Our results showed that HPV
typing by in situ hybridization is a useful tool for distinguishing between
low and high risk cervical lesions. Further studies are required to
elucidate risk factors associated with HPV infection and progression to
malignancy in Brazilian population.

===================================================================
58.) Prevalence of human papilloma virus 16 or 18 in cervical cancer in Hualien, eastern Taiwan. (TAIWAN)
===================================================================
Kao Hsiung I Hsueh Ko Hsueh Tsa Chih 1997 May;13(5):315-9

Hsu YH, Wei TC, Horng IJ, Jan WC, Su IJ
Department of Pathology, Tzu-Chi General Hospital, Hualien, Taiwan,
Republic of China.

In order to determine the association of human papilloma virus (HPV) with
cervical cancer of patients in the Hualien area, we analyzed 40 cervical
cancer specimens using polymerase chain reaction (PCR) to detect the
presence of HPV type 16 (HPV-16) and type 18 (HPV-18) genomes. The results
showed that at least 70% (28/40) of the specimens had HPV DNA. Of the 37
squamous cell carcinomas of the cervix, HPV-16 was present in 25 cases
(68%) and HPV-18 in 2 (5.4%). HPV-16 DNA was detected in one of 2
adenocarcinomas and HPV-18 in a case of small cell carcinoma. Seven (87.5%)
of 8 specimens from aborigines were HPV-positive. These findings support a
role for HPV in the development of cervical cancer in the Hualien population

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59.) Human papillomavirus types 52 and 58 are prevalent in cervical cancers from Chinese women. (CHINA)
===================================================================
Int J Cancer 1997 Feb 7;70(4):408-11

Huang S, Afonina I, Miller BA, Beckmann AM
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center,
Seattle, WA, USA.

A substantial body of evidence has confirmed human papillomavirus (HPV)
infection as an etiologic agent in human cervical cancer. To evaluate the
association between HPV and cervical cancer in Chinese women, we examined
tumor specimens from women who lived in Shanghai, People's Republic of
China. Biopsies from 40 women, diagnosed with either squamous-cell
carcinoma (n = 35) or adenocarcinoma (n = 5) were tested for HPV DNA by
PCR. The HPV types present in tumors were determined either by
hybridization of PCR products with HPV type-specific probes or by PCR-based
sequencing. A total of 35 of the 40 cervical cancer specimens (87.5%)
contained HPV DNA. The following distribution and types were detected: 7.5%
HPV 16, 10% HPV 18, 20% HPVs 16 and 18, 15% HPV 52, 15% HPV 58, 12.5% HPVs
52 and 58 and 7.5% unclassified HPVs. In this population of Chinese women
with cervical cancer, HPV 52 and 58 were as prevalent as the "high-risk"
(for cervical cancer) viruses HPVs 16 and 18.

===================================================================
60.) Human papillomavirus infection and risk determinants for squamous intraepithelial lesion and cervical cancer in Japan. (JAPAN)
===================================================================
Jpn J Cancer Res 1997 Apr;88(4):376-84

Sasagawa T, Dong Y, Saijoh K, Satake S, Tateno M, Inoue M
Department of Obstetrics and Gynecology, School of Medicine, Kanazawa
University, Takara-machi.

A case control design was used to investigate human papillomavirus (HPV)
prevalence and risk factors associated with development of cervical
squamous intraepithelial lesion (SIL) and cervical cancer (CC) in Japan.
One hundred and twenty-three women with histologically confirmed SIL or CC
were compared to a control group of 778 cytologically normal women. With
the use of a polymerase chain reaction (PCR)-based method for detection of
low-risk (types 6 and 11) and high-risk (types 16, 18, 31, 33, 35, 52 and
58) HPVs, a high prevalence of HPV infection was observed in smokers among
the controls. Logistic regression analysis demonstrated that high-risk HPV
infection was the most significant risk determinant for LSIL (OR=9.4, 95%
CI=4.5-19), HSIL (OR=77, 95% CI=28-217) and CC (OR=97, 95% CI=35-269). It
also showed that unmarried women, women married for 5 to 19 years and
smokers represented high risk groups for SIL, while smokers and women with
a history of many pregnancies/parities had increased risk for CC. Smoking
was the only HPV infection-independent factor for CC, suggesting that
smoking may have a carcinogenic effect on the cervix. Since neither history
of other cancer nor family cancer history was associated with SIL or CC,
genetic factors appear to play little role in cervical carcinogenesis. The
risk for cervical neoplasia due to HPV infection increased after marriage
in Japan, suggesting a role for husbands as carriers of HPV transmission.
Protection from high-risk HPV infection may be of greatest importance for
prevention of cervical cancer.

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61.) Detection and typing of human papillomavirus in cervical carcinomas in Russian women: a prognostic study. (RUSSIA)
===================================================================
Cancer 1999 May 1;85(9):2011-6

van Muyden RC, ter Harmsel BW, Smedts FM, Hermans J, Kuijpers JC, Raikhlin
NT, Petrov S, Lebedev A, Ramaekers FC, Trimbos JB, Kleter B, Quint WG
Department of Gynecology, Reinier de Graaf Gasthuis, Delft, The Netherlands.

BACKGROUND: The correlation between human papillomavirus (HPV) infection
and tumor prognosis in 159 Russian women with cervical carcinoma was
investigated. The presence of various HPV types was correlated with the
histologic parameters of the carcinomas and with their immunoreactivity
with antibodies to p53, Ki-67-Ag, and bcl-2. METHODS: Formalin fixed,
paraffin embedded tissue specimens representing 159 cases of International
Federation of Gynecology and Obstetrics Stage I and II were used. HPV DNA
was detected by polymerase chain reaction (PCR) using a general primer set
that targets the L1 region and synthesizes a product of only 65 base pairs.
The HPV types were determined by direct sequencing and compared with known
HPV types. RESULTS: All 159 carcinomas were positive for HPV. HPV 16
(64.8%) was most frequently found, followed by HPV 18 (10.7%) and HPV 45
(8.2%). In 6 patients (3.8%), HPV types could not been further classified,
and these cases were therefore categorized as HPV X. Although a trend was
noted toward poorer prognosis for women with carcinomas harboring HPV types
16, 18, and 45 than for patients with carcinomas harboring HPV types 31,
33, 35, 52, 56, 58, and 68, the differences were not statistically
significant. The prevalence of adenocarcinoma and adenosquamous carcinoma
was higher among HPV 18 positive patients than among patients with the
other known HPV types (P=0.0002). CONCLUSIONS: The rate of HPV positivity
in these 159 cervical carcinomas was 100%. These findings challenge the
assumption that HPV negative cervical carcinomas exist. This high rate
might be attributed to the use of a new broad-spectrum HPV PCR test. HPV
typing in cervical carcinoma was not significantly related to clinical
outcome. HPV 18 was significantly more frequently found in adenocarcinoma
and adenosquamous carcinoma. The possibility of classifying HPV 45 as an
oncogenic high risk type should be considered.

===================================================================
62.) Serologic response to human papillomavirus type 16 (HPV-16) virus-like particles in HPV-16 DNA-positive invasive cervical cancer and cervical intraepithelial neoplasia grade III patients and controls from Colombia and Spain. (COLOMBIA AND SPAIN)
===================================================================
ARTICLE SOURCE: J Infect Dis (United States), Jul 1995, 172(1) p19-24
AUTHOR(S): Nonnenmacher B; Hubbert NL; Kirnbauer R; Shah KV; Munoz N; Bosch FX; de
Sanjose S; Viscidi R; Lowy DR; Schiller JT
ABSTRACT: A human papillomavirus (HPV) type 16 virus-like particle-based ELISA was used to
assess antivirion immune responses in 300 women participating in cervical cancer case-control
studies in Colombia and Spain. Virion IgG antibodies were detected in the sera of 51% and 59% of
women with HPV-16 DNA-positive invasive cervical cancer and 81% and 73% of women with
HPV-16 DNA-positive cervical intraepithelial neoplasia grade III (CIN III) in Colombia and Spain,
respectively. Capsid antibodies were detected in 22% and 3% of cancer controls (P .001) and in
43% and 10% of CIN III controls (P = .010) from Colombia and Spain, respectively. Since
Colombia has an 8-fold higher incidence of cervical cancer, these results demonstrate an association
between ELISA positivity and cancer risk. Capsid antibody responses did not correlate with
humoral responses of the same women to HPV-16 E6 and E7 oncoproteins.

===================================================================
63.) Detection of human papillomavirus-related oral verruca vulgaris among Venezuelans. (VENEZUELA)
===================================================================
ARTICLE SOURCE: J Oral Pathol Med (Denmark), Mar 1993, 22(3) p113-6
AUTHOR(S): Premoli-de-Percoco G; Galindo I; Ramirez JL; Perrone M; Rivera H
AUTHOR'S ADDRESS: Instituto de Investigaciones Raul Vicentelli, Facultad de Odontologia,
Universidad Central de Venezuela, Caracas.
ABSTRACT: A sensitive in situ hybridization test under low stringency conditions (LCS) with a set
of digoxigenin-labeled human papillomavirus mixed probes (D-L HPV MP) revealed a positive
reaction in 8 of 10 cases of oral verruca vulgaris (OVV). Ages ranged from 5 to 37 years with a
mean of 14.5 years. 50% of all cases were located intraorally on the hard palate, followed in
frequency by the commissures. These preliminary findings provide evidence of the role of HPV in
OVV from a sample of the Venezuelan population. We show that in situ hybridization conducted
under LSC is useful in HPV detection (regardless of the type) and the digoxigenin-labeling system is
a rapid, relatively easy and specific method. In addition, this technique permits the retrospective
evaluation of routinely processed material, thus widening the investigative spectrum for HPV.

===================================================================
64.) Oncogenic association of specific human papillomavirus types with cervical neoplasia. (USA, PERU, BRAZIL)
===================================================================
ARTICLE SOURCE: J Natl Cancer Inst (United States), Oct 1987, 79(4) p671-7
AUTHOR(S): Lorincz AT; Temple GF; Kurman RJ; Jenson AB; Lancaster WD
ABSTRACT: Molecular hybridization analysis of human papillomavirus (HPV) DNA from 190
cervical biopsy specimens from women in the United States, Brazil, and Peru revealed viral
sequences in 2 (9%) of 23 biopsy specimens of normal mature squamous epithelium, 7 (44%) of 16
biopsy specimens of metaplastic squamous epithelia, 60 (77%) of 78 cervical intraepithelial
neoplasia (CIN), 57 (89%) of 64 invasive squamous carcinomas, and 8 (89%) of 9 endocervical
adenocarcinomas. HPV typing by DNA hybridization revealed HPV 6 and HPV 11 sequences in
metaplastic squamous epithelia, CIN I, and CIN II, but not in CIN III lesions or invasive
carcinomas. HPV 16 was detected in metaplastic epithelium and in nearly half of the invasive
squamous carcinomas and adenocarcinomas. It was present in 31% of CIN lesions, increasing in
frequency with the severity of CIN from 20% of CIN I to 50% of CIN III. HPV 16 showed a
striking difference in geographic distribution, being detected in 36% of the carcinomas from the
United States compared to 64% of the carcinomas from Brazil and Peru. HPV 18 was found in
metaplastic epithelia and in 17% of carcinomas but in only 1% of CIN lesions. HPV 31 was not
found in metaplastic epithelium but was present in 6% of carcinomas and in 18% of CIN lesions. In
addition, a group of uncharacterized HPVs, not corresponding to any of the probes used, was found
in 5% of normal and metaplastic epithelia and in 18% of CIN and 19% of invasive cancers. These
results suggest that individual HPV types that infect the cervix have varying degrees of oncogenic
association. HPV 6 and HPV 11 appear to have very little oncogenic association, HPV 31 has low
oncogenic association, and HPV 16 and HPV 18 have high oncogenic association.

===================================================================
65.) Chromosome fragility in lymphocytes of women with cervical uterine lesions produced by human papillomavirus. (ECUADOR)
===================================================================
ARTICLE SOURCE: Cancer Genet Cytogenet (United States), Apr 1992, 59(2) p173-6
AUTHOR(S): Paz-y-Mino C; Ocampo L; Narvaez R; Narvaez L
AUTHOR'S ADDRESS: Departamento de Ciencias Biologicas, Facultad de Ciencias Exactas y
Naturales, P. Universidad Catolica del Ecuador, Quito.
ABSTRACT: We studied 30 women with cervical lesions that showed human papillomavirus
infection (HPV). Cervical HPV infection was diagnosed by cytology, histology,
immunohistochemistry, and electron microscopy, as well as by DNA viral hybridization in situ with 6,
11, 16, and 18 HPV types. Three groups of patients were studied: 15 women infected by HPV of 6
and 11 types with koilocytic lesions and benign evolution, 15 women infected by HPV of 16 and 18
types with koilocytic lesions and malignant evolution, and 15 normal women without cervical lesions
who served as controls. For each group, chromosome fragility was studied in peripheral blood
lymphocytes. Aphidicolin (AP) was used as a clastogenic agent at a concentration of 0.12 microM.
There were significant differences (p less than 0.001) between the control population and the
patients affected by HPV. There were also significant differences (p less than 0.001) between the
two groups infected with HPV. Our findings support the concept that chromosome fragility could
serve as a cytogenetic marker to measure evolution, prognosis, and treatment of cervical lesion
associated with HPV.

===================================================================
66.) Multifocal papilloma virus epithelial hyperplasia [see comments] (GUATEMALA)
===================================================================
COMMENTS: Comment in: Oral Surg Oral Med Oral Pathol 1994 Dec; 78(6):680
ARTICLE SOURCE: Oral Surg Oral Med Oral Pathol (United States), Jun 1994, 77(6) p631-5
AUTHOR(S): Carlos R; Sedano HO
ABSTRACT: Multifocal papilloma virus epithelial hyperplasia is an infection of the oral mucosa
produced by human papilloma virus types 13 and 32, which primarily bilaterally affects lips, lateral
borders of tongue, and buccal mucosa. The attached oral mucosa, floor of mouth, soft palate, and
oropharynx are sites that appear not to be affected. This study comprises 110 patients with
multifocal papilloma virus epithelial hyperplasia identified over a period of 3 years in Guatemala City
and neighboring rural areas. All but four patients were younger than 18 years of age. More than one
affected patient was observed in several families. All but three cases occurred in patients living in
extreme poverty (annual family income less than $1,200 in U.S. dollars). Biopsies of 60 lesions
demonstrated acanthosis and nuclear degeneration within the epithelium. We suggest that the
eponym Heck's disease be abandoned because this disease was described in the Latin-American
literature before the initial description in the American literature. We propose the term multifocal
papilloma virus epithelial hyperplasia, which best describes the nature and multifocality of this
disease.

===================================================================
67.) Genital human papillomavirus infection in Panama City prostitutes. (PANAMA)
===================================================================
ARTICLE SOURCE: J Infect Dis (United States), Oct 1989, 160(4) p599-603
AUTHOR(S): Reeves WC; Arosemena JR; Garcia M; de Lao SL; Cuevas M; Quiroz E; Caussy
D; Rawls WE
ABSTRACT: Little is known of the natural history of genital human papillomavirus (HPV) infections
in women from high-risk populations. Samples were collected from 183 Panama City prostitutes and
assessed for HPV (filter in situ DNA hybridization) and for sexually transmitted agents. The cohort
was followed for 8 mo; 51% of subjects completed four monthly return visits and 16% were
sampled eight times. The proportion of women found infected with HPV increased significantly with
increasing numbers of consecutive samples tested; 38 (21%) of 183 women were positive after one
visit and 46 (82%) of 56 who completed six visits were infected. The pattern of viral detection over
time was not random, which implied that most prostitutes were persistently infected with genital
HPVs and that either scattered foci of infection or periodic reactivation of latent virus occurred. Our
findings suggest that multiple sampling is necessary to accurately estimate HPV infection rates and to
define whether patterns of DNA expression are present.

===================================================================
68.) Risk factors for genital papillomavirus infection in populations at high and low risk for cervical cancer. (PANAMA)
===================================================================
ARTICLE SOURCE: J Infect Dis (United States), Oct 1994, 170(4) p753-8
AUTHOR(S): Reeves WC; Gary HE Jr; Johnson PR; Icenogle JP; Brenes MM; de Britton RM;
Dobbins JG; Schmid DS
ABSTRACT: This study sought to determine risk factors for genital infection with papillomavirus
(HPV) in Panamanian women 20-49 years old. Subjects were randomly selected from Herrera and
Panama provinces (cervical cancer incidence 79 and 25/100,000, respectively). Participants were
interviewed to determine sexual behavior. Cervicovaginal lavage specimens were obtained to test for
HPV DNA by commercial dot blot hybridization. HPV-16/18 DNA was detected significantly more
frequently (5%) in Panama than Herrera (2%) samples (P = .002). Clearly, infection with high-risk
HPV types alone cannot account for the differences in cervical cancer incidence between the two
populations. HPV-16/18 detection decreased with increasing years of sexual experience among all
women in Panama and among women with multiple partners in Herrera. However, HPV-16/18
detection did not change with sexual experience among monogamous women in Herrera. Thus, the
epidemiology of HPV is complex and reflects both virus- and population-specific factors.

===================================================================
69.) Demonstration of multiple HPV types in normal cervix and in cervical squamous cell carcinoma using the polymerase chain reaction on paraffin wax embedded material. (ENGLAND)
===================================================================
ARTICLE SOURCE: J Clin Pathol (England), Jan 1990, 43(1) p52-6
AUTHOR(S): Griffin NR; Bevan IS; Lewis FA; Wells M; Young LS
AUTHOR'S ADDRESS: Department of Pathology, University of Leeds, England.
ABSTRACT: The prevalence of human papilloma virus (HPV) types 6, 11, 16 and 18 was
investigated using the polymerase chain reaction on formalin fixed, paraffin wax embedded material
in 19 cases of cervical squamous cell carcinoma and in 10 normal cervices. HPV DNA was
detected in 16 of 19 carcinomas, with multiple types present in 11 of these. HPV 16 or 18, or both,
were present in all cases in which HPV was shown. Six of 10 cases of normal cervix contained
HPV; five of these contained two or more HPV types, including HPV 16 or 18, or both. This study
shows the feasibility of using the PCR on paraffin wax embedded material and indicates a high rate
of carriage of multiple HPV types in both normal and neoplastic cervix.

===================================================================
70.) Morphological correlation of human papillomavirus infection of matched cervical smears and biopsies from patients with persistent mild cervical cytological abnormalities. (ENGLAND)
===================================================================
ARTICLE SOURCE: Hum Pathol (United States), Sep 1995, 26(9) p951-5
AUTHOR(S): Herrington CS; Evans MF; Gray W; McGee JO
ABSTRACT: Human papillomavirus (HPV) analysis of cytological material has been advocated for
determining those patients with low-grade cervical cytological abnormalities who have current
high-grade squamous intraepithelial lesions (SILs). In this study, we analyzed concurrent cervical
smears and biopsies from 167 patients with Papanicolaou (Pap) smears showing persistent atypical
squamous cells of uncertain significance (ASCUS) or low grade SILs (1) to compare the detection
of HPV by nonisotopic in situ hybridization (NISH) on matched smears and biopsies; (2) to analyze
the type and distribution of NISH signal within lesions; and (3) to define further the ability of NISH
techniques to distinguish between patients with low- and high-grade SIL. Whether present in cervical
smears or biopsies, high-risk HPV types (16, 18, 31, 33, and related types) were significantly
associated with high-grade SILs (P .001) but were found in 15% of low-grade SILs. Ninety percent
of high grade lesions were directly infected by these HPV types, and good concordance (92.2%)
was found between NISH analysis of matched cervical smears and biopsies, indicating accurate
colposcopic targetting of biopsies and excision specimens. Punctate signal morphology, which
correlates with viral integration, was associated with high-grade SILs but was also observed in two
low-grade SILs. Although the presence of high-risk HPV types in low-grade SILs limits the
predictive ability of HPV testing by this means in this group of patients, those patients with high-risk
HPV infection of low-grade SILs may be a greater risk of progression to high-grade SIL or invasive
carcinoma. If this were the case, HPV testing would be of potential value in the management of
patients with low-grade cytological abnormalities.

===================================================================
71.) Epidermodysplasia verruciformis in Africans. (SOUTH AFRICA)
===================================================================
ARTICLE SOURCE: Int J Dermatol (United States), Nov 1993, 32(11) p806-10
AUTHOR(S): Jacyk WK; De Villiers EM
ABSTRACT: BACKGROUND. Epidermodysplasia verruciformis (EV) is a rare cutaneous
disorder characterised by persistent, refractory infection with human papillomaviruses (HPV).
Although EV does not seem to have racial or geographic preference, there is a scarcity of reports on
its occurrence in Africans. METHODS. Twenty Africans with EV were studied, and the literature on
this condition in Africans was reviewed. Virologic studies were performed on 10 patients.
RESULTS. Three types of lesions were observed: flat warts, pityriasis versicolor-like macules, and
seborrheic keratosis-like changes. Malignant transformation occurred in only one patient. HPV-3
was isolated only from flat warts, HPV-5 and HPV-17 were isolated only from PV-like lesions,
whereas an HPV-5-related type was found in all three types of changes. HPV-5-related type
revealed DNA that was related but not identical to any of the viruses in the HPV-5 group. This
particular type was isolated from all five South African patients with EV in whom virologic studies
were performed. CONCLUSIONS. The benign nature of EV in dark-skinned Africans has been
confirmed. Four HPV types have been isolated, of which HPV-related type was found in all South
African patients with EV and in all types of skin changes, regardless of their morphology. African
patients with EV frequently present seborrheic keratosis-like changes.

===================================================================
72.) Transmissibility and treatment failures of different types of human papillomavirus. (ISRAEL)
===================================================================
ARTICLE SOURCE: Obstet Gynecol (United States), Mar 1989, 73(3 Pt 1) p308-11
AUTHOR(S): Gal D; Friedman M; Mitrani-Rosenbaum S
ABSTRACT: In order to evaluate the transmissibility and treatment failures of different types of
human papillomavirus (HPV), we obtained biopsy specimens from genital lesions related to HPV in
113 women prior to laser therapy. Sixty-eight had condylomata acuminata, 14 had flat condyloma,
and 31 had cervical intraepithelial neoplasia with or without condylomata. Of 76 male sexual
partners examined colposcopically, 58 (76%) had HPV-related lesions. All biopsy specimens were
analyzed for specific type of HPV DNA by Southern blot hybridization with probes for HPVs 6, 11,
16, and 18. Sixty-one women had HPV 6 or 11 (6/11), 40 had HPV 16 or 18 (16/18), and in 12
the analysis was negative for these types of viral DNA. Deoxyribonucleic acid analysis of biopsy
specimens from recurrent lesions showed the same type of viral DNA as in the primary lesion.
Significantly more male partners (28 of 47) with the same HPV type were found among women with
HPV 6/11 than among women with HPV 16/18 (P less than .005). Patients with HPV 16/18 had
significantly more recurrences (14 of 40) after laser therapy than patients with HPV 6/11 (six of 60)
(P less than .001).

===================================================================
73.) High frequency of detection of epidermodysplasia verruciformis-associated human papillomavirus DNA in biopsies from malignant and premalignant skin lesions from renal transplant recipients. (THE NETHERLANDS)
===================================================================
ARTICLE SOURCE: J Invest Dermatol (United States), Sep 1995, 105(3) p367-71
AUTHOR(S): de Jong-Tieben LM; Berkhout RJ; Smits HL; Bouwes Bavinck JN; Vermeer BJ; van der Woude FJ; ter Schegget J
AUTHOR'S ADDRESS: Department of Dermatology, University Hospital Leiden, The Netherlands.
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: Based on immunologic and epidemiologic data, it is plausible that skin cancer in renal transplant recipients is associated with human papillomaviruses (HPV). At present, conflicting evidence exists concerning the presence of HPV DNA in these cancers. We recently described a nested polymerase chain reaction method that enables the detection of all previously isolated epidermodysplasia verruciformis (EV)-associated HPVs. We now describe the detection of EV-associated HPV DNA in 49 (80%) of 61 biopsies from squamous cell carcinomas, in four (50%) of eight basal cell carcinomas, in 14 (93%) of 15 actinic keratoses, in two (40%) of five cases of Bowen's disease, and in four (57%) of seven keratoacanthomas. HPV DNA typing revealed that all detected HPV types belonged to the EV-associated HPV types. A wide spectrum of EV-associated HPVs was found, including six putative new HPV types. In a high percentage of the lesions more than one HPV type was detected. We often found the same HPV types in different skin biopsies from both malignant and premalignant lesions from the same patient. The high frequency of detection of EV-associated HPV types in biopsies from malignant and premalignant lesions is in agreement with the hypothesis that EV-associated HPVs are involved in the pathogenesis of skin cancer in renal transplant recipients.
 

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