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Goal: To determine type-specific seroprevalence of herpes simplex viruses (HSV-1 and HSV-2) and HSV-2 risk factors. Study Design: Six-hundred fifty eight middle-aged control women (hospital-based in 4 of 6 countries) from a multicenter cervical cancer case--control study participated from 1985 to 1997. Type-specific serum IgG antibodies against HSV-1 and HSV-2 were detected with Western Blot. Results: HSV-1 seroprevalence was 89% to 100% everywhere except Thailand (51%). HSV-2 seroprevalence ranged from 9% (Spain) to 57% (Colombia), and was independently associated with having [greater than or equal to] 2 lifetime sexual partners overall [Odds ratio (OR), 2.1; 95% confidence interval (CI) 2.5-3.1], and in Morocco (OR, 2.7; 95% CI, 1.2-6.1) and Thailand (OR, 4.4; 95% CI, 1.3-15.4), and with being unmarried in Colombia, Peru, Spain, but not significantly in Mali. Women whose male partner's sexual debut was [less than or equal to] 17 years had a higher HSV-2 risk (OR, 4.3 95% CI, 1.3-13.7). Conclusions: HSV-2 seroprevalence in middle-aged women varied over 4-fold and was associated with riskier sexual behaviors in women and their male partners.

Background: Limited data are available on whether sampling from the penile shaft or urethra increases detection of penile HPV infection in men beyond that found in the glans and coronal sulcus. Methods: Within a randomized clinical trial, a validation study of penile sampling was conducted in Kisumu, Kenya. Young men (18-24 years) were invited to provide penile exfoliated cells using prewetted Dacron swabs to determine the best site for HPV detection, [beta]-Globin gene PCR and HPV DNA type GP5 +/6+ PCR status were ascertained from 3 anatomical sites. Results: A total of 98 young HIV-seronegative, uncircumcised men participated. Penile HPV prevalence varied by anatomical site: 50% in penile exfoliated cells from the glans, coronal sulcus, and inner foreskin tissue; 43% in the shaft and external foreskin tissue; and 18% in the urethra (P Discussion: Penile HPV prevalence was approximately 50% among young men in Kisumu, Kenya. Urethral sampling for HPV detection in men added no sensitivity for HPV detection over that found from sampling the glans/coronal sulcus and penile shaft. These data will help inform studies on HPV transmission dynamics, and on the efficacy of HPV prophylactic vaccines on penile HPV carriage in men.

Objectives: Better information on the prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection is needed in many world areas. Study Design: Cross-sectional study of population-based samples of nonpregnant women aged 15 to 44 years in Nigeria, Colombia, Argentina, Vietnam (2 areas), China, Thailand (2 areas), Korea, and Spain. 5,328 consenting women aged 15 to 44 years participated. Exfoliated cervical cells were collected and testing for CT and NG and human papillomavirus (HPV) was done using PCR-based assays. Results: Age-standardized CT prevalence ranged between 0.2% (95% confidence interval, CI: 0.0-0.7%) in Spain and 5.6% (95% CI: 3.4-7.8%) in Nigeria. NG ranged between 0% (with broad CIs) in several areas and 2.6% (95% CI: 1.0-4.2%) in Nigeria. Prevalence of CT in all areas combined was greater in women aged 15 to 24 (4.5; 95% CI: 3.4-5.8%) than 25 to 44 (2.6; 95% CI: 2.1-3.1%), whereas NG prevalence was similar in the 2 age groups (0.3%). The only significant risk factors were NG infection (for CT), CT infection (for NG) and infection with high-risk HPV types (for both). Conclusions: The prevalence of CT and, most notably, NG was relatively low in a variety of countries. Our findings, however, do not apply to subsets of high-risk women who are likely to be underrepresented in our population-based samples.

Background: Most cancers of the uterine cervix are squamous cell carcinomas. Although the incidence of such carcinomas of the uterine cervix has declined over time, that of cervical adenocarcinoma has risen in recent years. The extent to which human papillomavirus (HPV) infection and cofactors may explain this differential trend is unclear. Methods: We pooled data from eight case-control studies of cervical cancer that were conducted on three continents. A total of 167 case patients with invasive cervical adenocarcinoma (112 with adenocarcinoma and 55 with adenosquamous carcinoma) and 1881 hospital-based control subjects were included. HPV DNA was analyzed in cervical specimens with the GP5+/6+ general primer system followed by type-specific hybridization for 33 HPV genotypes. Blood samples were analyzed for chlamydial and herpes simplex virus 2 (HSV-2) serology. Multivariable unconditional logistic regression modeling was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs). All tests of statistical significance were two-sided. Results: The adjusted overall odds ratio for cervical adenocarcinoma in HPV-positive women compared with HPV-negative women was 81.3 (95% CI = 42.0 to 157.1). HPV 16 and HPV 18 were the two most commonly detected HPV types in case patients and control subjects. These two types were present in 82% of the patients. Cofactors that showed clear statistically significant positive associations with cervical adenocarcinoma overall and among HPV-positive women included never schooling, poor hygiene, sexual behavior-related variables, long-term use of hormonal contraception, high parity, and HSV-2 seropositivity. Parity had a weaker association with adenocarcinoma and only among HPV-positive women. Use of an intrauterine device (IUD) had a statistically significant inverse association with risk of adenocarcinoma (for ever use of an IUD compared with never use, OR = .41 [95% CI = 0.18 to 0.931). Smoking and chlamydial seropositivity were not associated with disease. Conclusions: HPV appears to be the key risk factor for cervical adenocarcinoma. HPV testing in primary screening using current mixtures of HPV types and HPV vaccination against main HPV types should reduce the incidence of this cancer worldwide.

Background: Transcriptionally active high-risk human papilloma viruses (HPVs), particularly HPV type 16 (HPV16), are found in a subset of head and neck squamous-cell carcinomas (HNSCCs). HPV16-associated carcinogenesis is mediated by expression of the viral E6 and E7 oncoproteins, which cause deregulation of the cell cycle by inactivating p53 and pRb, respectively. We tested the hypothesis that HPV-associated HNSCCs display a pattern of genetic alterations different from those of HNSCCs without HPV DNA. Methods: Polymerase chain reaction-based assays were used to examine 143 consecutive HNSCCs (106 of the oral cavity and 37 of the oropharynx) for the presence of HPV DNA and for viral E6 and/or E7 messenger RNA (mRNA) expression. The HPV DNA- and E6 and E7 mRNA-positive HNSCCs and an equal number of HPV DNA-negative HNSCCs were further analyzed for mutations in TP53, the gene encoding p53, and for allelic loss of 28 microsatellite markers at chromosome arms 3p, 6q, 8p, 9p, 13q, 17p, and 18q, including markers located in regions of chromosome arms 9p and 17p that harbor genes involved the p53 and pRb pathways. All statistical tests were two-sided. Results: Twenty-four (16.7%) of the 143 HNSCCs were positive for HPV16 DNA, and 12 of these HNSCCs (8.4% of total number) expressed E6 and E7 mRNAs. None of the HPV DNA- and E6/E7 mRNA-positive tumors had TP53 gene mutations, whereas nine (75%) of the 12 HPV DNA-negative tumors had such mutations (P

Background: Cervical carcinogenesis is initiated by infection with high-risk (i.e., carcinogenic) human papillomavirus (HPV) types. The subsequent progression from premalignant cervical intraepithelial neoplasia (CIN) to invasive cancer is driven by both genetic and epigenetic processes. We assessed the role of the gene encoding the adhesion molecule tumor suppressor in lung cancer 1 (TSLC1) in this progression. Methods: We analyzed TSLC1 gene expression by real-time quantitative reverse transcription-polymerase chain reaction, promoter methylation by sodium bisulfite genomic DNA sequencing, and allelic loss by microsatellite analysis in primary keratinocytes, in four non-tumorigenic HPV-immortalized human keratinocyte cell lines, and in 11 human cervical cancer cell lines that were positive for a high-risk HPV DNA type and in normal cervical epithelial cells. We transfected cervical cancer SiHa cells that did not express TSLC1 mRNA with an expression vector containing the TSLC1 complementary DNA (cDNA) or an empty vector and analyzed transfectants for anchorage-independent growth and tumorigenicity in nude mice. We also examined TSLC1 promoter methylation in premalignant cervical lesions and in cervical carcinomas and smears. All statistical tests were two-sided. Results: TSLCI mRNA was strongly reduced, relative to levels in primary keratinocytes, or absent in 10 (91%) of 11 cervical carcinoma cell lines but in none (0%) of the four HPV-immortalized cell lines (difference = 91%, 95% confidence interval [CI] = 74% to 100%; P = .004). The TSLC1 promoter was hypermethylated, relative to normal foreskin and cervical epithelial cells, in nine (82%) of the 11 cervical carcinoma cell lines but in none (0%) of the four HPV-immortalized cell lines (difference = 82%, 95 CI = 59% to 100%; P = .01). Seven (88%, 95% CI = 47% to 100%) of the eight SiHa/TSLC1 transfectants displayed a marked reduction in anchorage-independent growth (i.e., 0-100 colonies per 5000 cells) compared with none of the four (0%, 95% CI = 0% to 60%) SiHa transfectants bearing the empty vector (i.e., SiHa/hygro transfectants; difference = 88%, 95% CI = 65% to 100%; P = .01) or untransfected SiHa cells. All seven mice (100%, 95% CI = 59% to 100%) injected with untransfected SiHa cells or SiHa/hygro transfectants displayed tumors of at least 50 [mm.sup.3] by 2-6 weeks after injection compared with none of eight mice (0%, 95% CI = 0% to 37%) injected with the SiHa/TSLC1 transfectants (difference = 100%, 95% CI = 68% to 100%; P

Background: Human papillomavirus (HPV), the causal agent of cervical cancer, appears to be involved in the etiology of cancer of the oral cavity and oropharynx. To investigate these associations, we conducted a multicenter case-control study of cancer of the oral cavity and oropharynx in nine countries. Methods: We recruited 1670 case patients (1415 with cancer of the oral cavity and 255 with cancer of the oropharynx) and 1732 control subjects and obtained an interview, oral exfoliated cells, and blood from all participants and fresh biopsy specimens from case patients. HPV DNA was detected by polymerase chain reaction (PCR). Antibodies against HPV16L1, E6, and E7 proteins in plasma were detected with enzyme-linked immunosorbent assays. Multivariable models were used for case--control and case--case comparisons. Results: HPV DNA was detected in biopsy specimens of 3.9% (95% confidence interval [CI] = 2.5% to 5.3%) of 766 cancers of the oral cavity with valid PCR results and 18.3% (95% CI = 12.0% to 24.7%) of 142 cancers of the oropharynx (oropharynx and tonsil combined) with valid PCR results. HPV DNA in cancer biopsy specimens was detected less frequently among tobacco smokers and paan chewers and more frequently among subjects who reported more than one sexual partner or who practiced oral sex. HPV16 DNA was found in 94.7% of HPV DNA--positive case patients. HPV DNA in exfoliated cells was not associated with cancer risk or with HPV DNA detection in biopsy specimens. Antibodies against HPV16L1 were associated with risk for cancers of the oral cavity (odds ratio [OR] = 1.5, 95% CI = 1.1 to 2.1) and the oropharynx (OR = 3.5, 95% CI = 2.1 to 5.9). Antibodies against HPV16 E6 or E7 were also associated with risk for cancers of the oral cavity (OR = 2.9, 95% CI = 1.7 to 4.8) and the oro-pharynx (OR = 9.2, 95% CI = 4.8 to 17.7). Conclusions: HPV appears to play an etiologic role in many cancers of the oropharynx and possibly a small subgroup of cancers of the oral cavity. The most common HPV type in genital cancers (HPV16) was also the most common in these tumors. The mechanism of transmission of HPV to the oral cavity warrants further investigation.

Background and Objective: Human papillomavirus (HPV) is a major cause of invasive cervical cancer. Identification of HPV determinants might allow for targeting of high-risk groups for cervical cancer. Goal: The goal was to estimate the HPV prevalence and its determinants among women from the general population of Barcelona. Study Design: We studied a random sample of female residents in metropolitan Barcelona, Spain (n = 973). Information was obtained through personal interviews and laboratory testing of cervical exfoliated cells. HPV was detected using a GP5+/6+ polymerase chain reaction assay. Results: The average age of participants was 43 years (standard deviation = 16.1 y) and the percentage of lifetime monogamy was 79%. The age-adjusted HPV prevalence was 3.0%. Independent HPV determinants were being born overseas (odds ratio [OR], 8.1; 95% confidence interval [CI], 1.9-33.5), being divorced (OR, 6.7; 95% CI, 1.9-24.3), reporting more than one sexual partner (OR, 2.6; 95% CI, 1.0-6.5), and smoking marijuana and related products (OR, 5.2; 95% CI, 1.2-21.7). Use of condoms with regular partner was protective (OR, 0.14; 95% CI, 0.02-1.0). Conclusion: The study confirms a low overall HPV prevalence in a largely monogamous population. The protection observed with condom use needs further evaluation.