Worldwide use of HPV self-sampling for cervical cancer screening.

An increasing body of evidence supports the validity of self-sampling as an alternative to clinician collection for primary Human Papillomavirus (HPV) screening. Self-sampling effectively reaches underscreened women and can be a powerful strategy in low- and high-resource settings for all target ages. This work aims to summarize the current use of HPV self-sampling worldwide. It is part of a larger project that describes cervical cancer screening programmes and produces standardized coverage estimates worldwide. A systematic review of the literature and official documents supplemented with a formal World Health Organisation country consultation was conducted. Findings show that the global use of HPV self-sampling is still limited. Only 17 (12%) of countries with identified screening programs recommend its use, nine as the primary collection method, and eight to reach underscreened populations. We identified 10 pilots evaluating the switch to self-sampling in well-established screening programs. The global use of self-sampling is likely to increase in the coming years. COVID-19's pandemic has prompted efforts to accelerate HPV self-sampling introduction globally, and it is now considered a key element in scaling up screening coverage. The information generated by the early experiences can be beneficial for decision-making in both new and existing programs.

Long-term predictors of residual or recurrent cervical intraepithelial neoplasia 2-3 after treatment with a large loop excision of the transformation zone: a retrospective study.

OBJECTIVE: To assess the long-term risk factors predicting residual/recurrent cervical intraepithelial neoplasia (CIN 2-3) and time to recurrence after large loop excision of the transformation zone (LLETZ). DESIGN: Retrospective study. SETTING: Colposcopy clinic. POPULATION: 242 women with CIN 2-3 treated between 1996 and 2006 and followed up until June 2016. METHODS: Age, margins, and high-risk human papillomavirus (HR-HPV) were estimated using Cox proportional hazard and unconditional logistic regression models. The cumulative probability of treatment failure was estimated by Kaplan-Meier analysis. MAIN OUTCOME MEASURE: Histologically confirmed CIN 2-3, HR-HPV, margins, age. RESULTS: CIN 2-3 was associated with HR-HPV (HR = 30.5, 95% confidence interval [CI] = 3.80-246.20), age >35 years (HR = 5.53, 95% CI = 1.22-25.13), and margins (HR = 7.31, 95% CI = 1.60-33.44). HR-HPV showed a sensitivity of 88.8% and a specificity of 80%. Ecto+ /endocervical+ (16.7%), uncertain (19.4%) and ecto- /endocervical+ margins (9.1%) showed a higher risk of recurrence (odds ratio [OR] = 13.20, 95% CI = 1.02-170.96; OR = 15.84, 95% CI = 3.02-83.01; and OR = 6.60, 95% CI = 0.88-49.53, respectively). Women with involved margins and/or who were HR-HPV positive had more treatment failure than those who were HR-HPV negative or had clear margins (P-log-rank <0.001). CONCLUSIONS: HR-HPV and margins seem essential for stratifying post-LLETZ risk, and enable personalised management. Given that clear margins present a lower risk, a large excision may be indicated in older women to reduce the risk. TWEETABLE ABSTRACT: After LLETZ for CIN 2-3, recurrences appear more often in women with positive HR-HPV and involved margins and aged over 35.

Differential HPV16 variant distribution in squamous cell carcinoma, adenocarcinoma and adenosquamous cell carcinoma.

Human Papillomavirus 16 (HPV16) causes 70% of invasive cervical cancers (ICC) worldwide. Interaction between HPV16 genetic diversity, host genetics and target tissue largely determine the chances to trigger carcinogenesis. We have analyzed the differential prevalence of viral variants in 233 HPV16-monoinfected squamous (SCC), glandular (ADC) and mixed (ADSC) ICCs from four continents, assessing the contribution of geographical origin and cancer histology. We have further quantified the contribution of viral variants and cancer histology to differences in age at tumor diagnosis. The model fitted to the data explained 97% of the total variance: the largest explanatory factors were differential abundance among HPV16 variants (78%) and their interaction with cancer histology (9.2%) and geography (10.1%). HPV16_A1-3 variants were more prevalent in SCC while HPV16_D variants were increased in glandular ICCs. We confirm further a non-random geographical structure of the viral variants distribution. ADCs were diagnosed at younger ages than SCCs, independently of the viral variant triggering carcinogenesis. HPV16 variants are differentially associated with histological ICCs types, and ADCs are systematically diagnosed in younger women. Our results have implications for the implementation of cervical cancer screening algorithms, to ensure proper early detection of elusive ADCs.

Occupational exposure to endocrine disruptors and lymphoma risk in a multi-centric European study.

BACKGROUND: Incidence rates of lymphoma are usually higher in men than in women, and oestrogens may protect against lymphoma. METHODS: We evaluated occupational exposure to endocrine disrupting chemicals (EDCs) among 2457 controls and 2178 incident lymphoma cases and subtypes from the European Epilymph study. RESULTS: Over 30 years of exposure to EDCs compared to no exposure was associated with a 24% increased risk of mature B-cell neoplasms (P-trend=0.02). Associations were observed among men, but not women. CONCLUSIONS: Prolonged occupational exposure to endocrine disruptors seems to be moderately associated with some lymphoma subtypes.

Interlaboratory reproducibility and proficiency testing within the human papillomavirus cervical cancer screening program in Catalonia, Spain.

In Catalonia, a screening protocol for cervical cancer, including human papillomavirus (HPV) DNA testing using the Digene Hybrid Capture 2 (HC2) assay, was implemented in 2006. In order to monitor interlaboratory reproducibility, a proficiency testing (PT) survey of the HPV samples was launched in 2008. The aim of this study was to explore the repeatability of the HC2 assay's performance. Participating laboratories provided 20 samples annually, 5 randomly chosen samples from each of the following relative light unit (RLU) intervals: <0.5, 0.5 to 0.99, 1 to 9.99, and ≥10. Kappa statistics were used to determine the agreement levels between the original and the PT readings. The nature and origin of the discrepant results were calculated by bootstrapping. A total of 946 specimens were retested. The kappa values were 0.91 for positive/negative categorical classification and 0.79 for the four RLU intervals studied. Sample retesting yielded systematically lower RLU values than the original test (P<0.005), independently of the time elapsed between the two determinations (median, 53 days), possibly due to freeze-thaw cycles. The probability for a sample to show clinically discrepant results upon retesting was a function of the RLU value; samples with RLU values in the 0.5 to 5 interval showed 10.80% probability to yield discrepant results (95% confidence interval [CI], 7.86 to 14.33) compared to 0.85% probability for samples outside this interval (95% CI, 0.17 to 1.69). Globally, the HC2 assay shows high interlaboratory concordance. We have identified differential confidence thresholds and suggested the guidelines for interlaboratory PT in the future, as analytical quality assessment of HPV DNA detection remains a central component of the screening program for cervical cancer prevention.

Occupational exposure to trichloroethylene and risk of non-Hodgkin lymphoma and its major subtypes: a pooled InterLymph [correction of IinterLlymph] analysis.

OBJECTIVES: We evaluated the association between occupational exposure to trichloroethylene (TCE) and risk of non-Hodgkin lymphoma (NHL) in a pooled analysis of four international case-control studies. METHODS: Overall, the pooled study population included 3788 NHL cases and 4279 controls. Risk of NHL and its major subtypes associated with TCE exposure was calculated with unconditional logistic regression and polytomous regression analysis, adjusting by age, gender and study. RESULTS: Risk of follicular lymphoma (FL), but not NHL overall or other subtypes, increased by probability (p=0.02) and intensity level (p=0.04), and with the combined analysis of four exposure metrics assumed as independent (p=0.004). After restricting the analysis to the most likely exposed study subjects, risk of NHL overall, FL and chronic lymphocytic leukaemia (CLL) were elevated and increased by duration of exposure (p=0.009, p=0.04 and p=0.01, respectively) and with the combined analysis of duration, frequency and intensity of exposure (p=0.004, p=0.015 and p=0.005, respectively). Although based on small numbers of exposed, risk of all the major NHL subtypes, namely diffuse large B-cell lymphoma, FL and CLL, showed increases in risk ranging 2-3.2-fold in the highest category of exposure intensity. No significant heterogeneity in risk was detected by major NHL subtypes or by study. CONCLUSIONS: Our pooled analysis apparently supports the hypothesis of an increase in risk of specific NHL subtypes associated with occupational exposure to TCE.

Antibodies against lytic and latent Kaposi's sarcoma-associated herpes virus antigens and lymphoma in the European EpiLymph case-control study.

BACKGROUND: Kaposi's sarcoma-associated herpes virus is associated with primary effusion lymphoma and multicentric Castleman's disease. METHODS: Seropositivity to lytic and latent Kaposi's sarcoma herpes virus (KSHV) antigens were examined in 2083 lymphomas and 2013 controls from six European countries. RESULTS: Antibodies against KSHV latent and lytic antigens were detectable in 4.5% and 3.4% of controls, respectively, and 3.6% of cases (P>0.05). The KSHV seropositivity was associated with splenic marginal zone lymphoma (SMZL) (odds ratio (OR)=4.11, 95% confidence interval (CI)=1.57-10.83) and multiple myeloma (OR=0.31, 95% CI=0.11-0.85). CONCLUSION: The KSHV is unlikely to contribute importantly to lymphomagenesis among immunocompetent subjects. However, the observed association with SMZL may underline a chronic antigen mechanism in its aetiology.

Worldwide burden of cervical cancer in 2008.

BACKGROUND: The knowledge that persistent human papillomavirus infection is the main cause of cervical cancer has resulted in the development of assays that detect nucleic acids of the virus and prophylactic vaccines. Up-to-date and reliable data are needed to assess impact of existing preventive measures and to define priorities for the future. MATERIALS AND METHODS: Best estimates on cervical cancer incidence and mortality are presented using recently compiled data from cancer and mortality registries for the year 2008. RESULTS: There were an estimated 530,000 cases of cervical cancer and 275,000 deaths from the disease in 2008. It is the third most common female cancer ranking after breast (1.38 million cases) and colorectal cancer (0.57 million cases). The incidence of cervical cancer varies widely among countries with world age-standardised rates ranging from <1 to >50 per 100,000. Cervical cancer is the leading cause of cancer-related death among women in Eastern, Western and Middle Africa; Central America; South-Central Asia and Melanesia. The highest incidence rate is observed in Guinea, with ∼6.5% of women developing cervical cancer before the age of 75 years. India is the country with the highest disease frequency with 134,000 cases and 73 000 deaths. Cervical cancer, more than the other major cancers, affects women <45 years. CONCLUSIONS: In spite of effective screening methods, cervical cancer continues to be a major public health problem. New methodologies of cervical cancer prevention should be made available and accessible for women of all countries through well-organised programmes.

Appraisal of the burden of genital warts from a healthcare and individual patient perspective.

OBJECTIVE: Worldwide, genital warts, caused by human papillomavirus (HPV) is a common, sexually transmitted disease. The overall disease management strategy for genital warts should be determined not only by the prevalence, but also by the impact of the disease on individuals and society. The purpose of this study was therefore to investigate the epidemiological, economic and quality of life (QoL) burden of genital warts. METHODS: A systematic literature review was conducted on the epidemiology, QoL and management cost of genital warts in the USA, UK and France, based on studies published between 1998 and 2008. Due to scarcity of data, all studies reporting standardized QoL assessments among patients with genital warts were utilized, regardless of country of origin. Original studies were preferred over information cited in review articles. RESULTS: Data from three countries suggest that genital warts occur in 0.06-0.23% of the population each year. Despite the fact that spontaneous remissions occur frequently (up to 40%), patients often prefer immediate treatment. While treatment can be costly in absolute terms (€163-510 per treatment episode), these costs are lower compared with other sexually transmitted infections (STIs). Modest reductions in QoL have been noted, which may be mitigated through adequate patient education and support. CONCLUSIONS: While genital warts are an inconvenience for many patients, the occurrence may be lower than often quoted in the literature, and the economic burden on society is less than for other prominent STIs. However, concerted efforts to establish improved data collection and surveillance systems are needed in order to accurately define the burden of genital warts on individuals and society.

Does the number of doses matter? A qualitative study of HPV vaccination acceptability nested in a dose reduction trial in Tanzania.

BACKGROUND: The multi-dose regimen is a known barrier to successful human papillomavirus (HPV) vaccination. Emerging evidence suggests that one vaccine dose could protect against HPV. While there are clear advantages to a single dose schedule, beliefs about vaccine dosage in low and middle income countries (LMICs) are poorly understood. We investigated acceptability of dose-reduction among girls, and parents/guardians of girls, randomised to receive one, two or three doses in an HPV vaccine dose-reduction and immunobridging study (DoRIS trial) in Tanzania. METHODS: Semi-structured interviews with girls (n = 19), and parents/guardians of girls (n = 18), enrolled in the study and completing their vaccine course. RESULTS: Most participants said they entrusted decisions about the number of HPV vaccine doses to experts. Random allocation to the different dose groups did not feature highly in the decision to participate in the trial. Given a hypothetical choice, girls generally said they would prefer fewer doses in order to avoid the pain of injections. Parental views were mixed, with most wanting whichever dose was most efficacious. Nonetheless, a few parents equated a higher number of doses with greater protection. CONCLUSION: Vaccine trials and programmes will need to employ careful messaging to explain that one dose offers sufficient protection against HPV should emerging evidence from ongoing dose-reduction clinical trials support this.

Occupational exposure to solvents and risk of lymphoma subtypes: results from the Epilymph case-control study.

BACKGROUND: Several studies have suggested an association between occupational exposure to solvents and lymphoma risk. However, findings are inconsistent and the role of specific chemicals is not known. Objective To investigate the role of occupational exposure to organic solvents in the aetiology of B-cell non-Hodgkin's lymphoma (B-NHL) and its major subtypes, as well as Hodgkin's lymphoma and T-cell lymphoma. METHODS: 2348 lymphoma cases and 2462 controls participated in a case-control study in six European countries. A subset of cases were reviewed by a panel of pathologists to ensure diagnostic consistency. Exposure to solvents was assessed by industrial hygienists and occupational experts based on a detailed occupational questionnaire. RESULTS: Risk of follicular lymphoma significantly increased with three independent metrics of exposure to benzene, toluene and xylene (BTX) (combined p=4 x 10(-7)) and to styrene (p=1 x 10(-5)), and chronic lymphocytic leukaemia (CLL) risk increased with exposure to solvents overall (p=4 x 10(-6)), BTX (p=5 x 10(-5)), gasoline (p=8 x 10(-5)) and other solvents (p=2 x 10(-6)). Risk of B-NHL for ever exposure to solvents was not elevated (OR=1.1, 95% CI 1.0 to 1.3), and that for CLL and follicular lymphoma was 1.3 (95% CI 1.1 to 1.6) and 1.3 (95% CI 1.0 to 1.7), respectively. Exposure to benzene accounted, at least partially, for the association observed with CLL risk. Hodgkin's lymphoma and T-cell lymphoma did not show an association with solvent exposure. CONCLUSION: This analysis of a large European dataset confirms a role of occupational exposure to solvents in the aetiology of B-NHL, and particularly, CLL. It is suggested that benzene is most likely to be implicated, but we cannot exclude the possibility of a role for other solvents in relation to other lymphoma subtypes, such as follicular lymphoma. No association with risk of T-cell lymphoma and Hodgkin's lymphoma was shown.

Differences in the risk of cervical cancer and human papillomavirus infection by education level.

BACKGROUND: Cervical cancer risk is associated with low education even in an unscreened population, but it is not clear whether human papillomavirus (HPV) infection follows the same pattern. METHODS: Two large multicentric studies (case-control studies of cervical cancer and HPV prevalence survey) including nearly 20 000 women. GP5+/GP6+ PCR was used to detect HPV. RESULTS: Education level was consistently associated with cervical cancer risk (odds ratio (OR) for 0 and >5 years vs 1-5 years=1.50, 95% confidence interval (CI): 1.25-1.80 and 0.69, 95% CI: 0.57-0.82, respectively, P for trend <0.0001). In contrast, no association emerged between education level and HPV infection in either of the two IARC studies. A majority of the women studied had never had a Pap smear. The association between low education level and cervical cancer was most strongly attenuated by adjustment for age at first sexual intercourse and first pregnancy. Parity and screening history (but not lifetime number of sexual partners, husband's extramarital sexual relationships, and smoking) also seemed to be important confounding factors. CONCLUSION: The excess of cervical cancer found in women with a low socio-economic status seems, therefore, not to be explained by a concomitant excess of HPV prevalence, but rather by early events in a woman's sexually active life that may modify the cancer-causing potential of HPV infection.

Early age at first sexual intercourse and early pregnancy are risk factors for cervical cancer in developing countries.

Early age at first sexual intercourse (AFSI) has long been associated with an increased risk of invasive cervical carcinoma (ICC). Age at first pregnancy (AFP) and ICC have been investigated less, although AFSI and AFP are strongly interrelated in most developing countries. A pooled analysis of case-control studies on ICC from eight developing countries with 1864 cases and 1719 controls investigated the roles of AFSI, AFP, and ICC risk. Age at first sexual intercourse, AFP and age at first marriage (AFM) were highly interrelated and had similar ICC risk estimates. Compared with women with AFSI > or = 21 years, the odds ratio (OR) of ICC was 1.80 (95% CI: 1.50-2.39) among women with AFSI 17-20 years and 2.31 (95% CI: 1.85-2.87) for AFSI < or = 16 years (P-trend <0.001). No statistical interaction was detected between AFSI and any established risk factors for ICC. The ICC risk was 2.4-fold among those who reported AFSI and AFP at < or = 16 years compared with those with AFSI and AFP at > or = 21 years. These data confirm AFSI and AFB as risk factors for ICC in eight developing countries, but any independent effects of these two events could not be distinguished.

Laryngeal squamous cell carcinoma in HIV-positive patients: lack of association with human papillomavirus infection.

OBJECTIVES: Neoplasms associated with human papillomavirus (HPV) infection occur at increased frequency in patients with HIV infection/AIDS. Although laryngeal squamous cell carcinomas (LSCCs) in HIV-positive patients are uncommon, a higher incidence of this malignancy in HIV-positive patients than in the general population has been reported. As a proportion of LSCCs are associated with HPV in the general population, the clinicopathological features of a series of LSCCs developing in HIV-positive patients were evaluated to investigate the possible relationship with HPV infection, and infection with other oncogenic viruses. METHODS: All HIV-positive patients with LSCC diagnosed at a single institution from 1998 to 2007 were retrospectively evaluated. The clinicopathological features were analysed and tissues were tested by polymerase chain reaction (PCR), using the short PCR fragment 10 (SPF10) primer, a highly sensitive method for HPV DNA detection. Immunohistochemical studies for HIV p24, p16(INK4a) and p53 were performed. Epstein-Barr virus (EBV) and human herpes virus 8 (HHV-8) were also investigated. RESULTS: Six out of 4987 HIV-infected patients seen in this period in the Infectious Diseases Department developed LSCC (median age 41.5 years; male to female ratio 1:1). All patients were heavy smokers and the tumours presented at an advanced clinical stage. HPV was not detected in any tumour, not even in two patients with coexisting HPV-associated gynaecological neoplasm. Staining for HIV p24 and p16(INK4a) was negative, whereas p53 was positive in half the cases. EBV and HHV-8 were also negative. CONCLUSION: LSCC developing in HIV-positive patients is an infrequent neoplasm, not usually associated with HPV infection. It develops in young, heavy smokers and presents at an advanced clinical stage.

Health and economic impact of HPV 16 and 18 vaccination and cervical cancer screening in India.

Cervical cancer is a leading cause of cancer death among women in low-income countries, with approximately 25% of cases worldwide occurring in India. We estimated the potential health and economic impact of different cervical cancer prevention strategies. After empirically calibrating a cervical cancer model to country-specific epidemiologic data, we projected cancer incidence, life expectancy, and lifetime costs (I$2005), and calculated incremental cost-effectiveness ratios (I$/YLS) for the following strategies: pre-adolescent vaccination of girls before age 12, screening of women over age 30, and combined vaccination and screening. Screening differed by test (cytology, visual inspection, HPV DNA testing), number of clinical visits (1, 2 or 3), frequency (1 x , 2 x , 3 x per lifetime), and age range (35-45). Vaccine efficacy, coverage, and costs were varied in sensitivity analyses. Assuming 70% coverage, mean reduction in lifetime cancer risk was 44% (range, 28-57%) with HPV 16,18 vaccination alone, and 21-33% with screening three times per lifetime. Combining vaccination and screening three times per lifetime provided a mean reduction of 56% (vaccination plus 3-visit conventional cytology) to 63% (vaccination plus 2-visit HPV DNA testing). At a cost per vaccinated girl of I$10 (per dose cost of $2), pre-adolescent vaccination followed by screening three times per lifetime using either VIA or HPV DNA testing, would be considered cost-effective using the country's per capita gross domestic product (I$3452) as a threshold. In India, if high coverage of pre-adolescent girls with a low-cost HPV vaccine that provides long-term protection is achievable, vaccination followed by screening three times per lifetime is expected to reduce cancer deaths by half, and be cost-effective.

HPV vaccination of immunocompromised hosts.

It is well-established that immunocompromised people are at increased risk of HPV-related disease compared with those who are immunocompetent. Prophylactic HPV sub-unit vaccines are safe and immunogenic in immunocompromised people and it is strongly recommended that vaccination occur according to national guidelines. When delivered to immunocompromised populations, HPV vaccines should be given as a 3-dose regimen.

Worldwide distribution of human papillomavirus types in cytologically normal women in the International Agency for Research on Cancer HPV prevalence surveys: a pooled analysis.

BACKGROUND: The proportion of women infected with human papillomavirus (HPV) varies greatly across populations, as might the distribution of HPV types. We aimed to compare HPV-type distribution in representative samples of women from different world regions. METHODS: Women were randomly selected from the general population of 13 areas from 11 countries (Nigeria, India, Vietnam, Thailand, Korea, Colombia, Argentina, Chile, the Netherlands, Italy, and Spain). A standardised protocol was used for cervical specimen collection. All HPV testing was by GP5+/6+ PCR-based EIA. The proportion of HPV-positive women infected with different HPV types was compared by study area and between pooled regions with age-adjusted odds ratios (ORs) with corresponding 95% floating CIs. FINDINGS: 15 613 women aged 15-74 years without cytological abnormalities were included in a pooled analysis. Age-standardised HPV prevalence varied nearly 20 times between populations, from 1.4% (95% CI 0.5-2.2) in Spain to 25.6% (22.4-28.8) in Nigeria. Although both overall HPV prevalence and HPV16 prevalence were highest in sub-Saharan Africa, HPV-positive women in Europe were significantly more likely to be infected with HPV16 than were those in sub-Saharan Africa (OR 2.64, p=0.0002), and were significantly less likely to be infected with high-risk HPV types other than HPV16 (OR 0.57, p=0.004) and/or low-risk HPV types (OR 0.44. p=0.0002). Women from South America had HPV-type distribution in between those from sub-Saharan Africa and Europe. Heterogeneity between areas of Asia was significant. INTERPRETATION: Heterogeneity in HPV type distribution among women from different populations should be taken into account when developing screening tests for the virus and predicting the effect of vaccines on the incidence of infection.

Exposure to non-arsenic pesticides is associated with lymphoma among farmers in Spain.

OBJECTIVES: To estimate the risk of lymphoma among farmers in Spain. METHODS: This is a multicentre case control study conducted in Spain. Cases were subjects diagnosed with lymphoma according to the World Health Organization (WHO) classification in four hospitals between 1998-2002. Hospital controls were frequency matched to the cases by sex, age, and centre. All subjects were interviewed about jobs ever held in lifetime for at least one year and the exposures in those jobs were recorded. The risk of lymphomas among subjects ever having had a job as a farmer was compared with all other occupations. Farmers were analysed according to the type of farming job performed: crop farming, animal farming, and general farming. Occupational exposure was summarised into 15 main categories: organic dust, radiation, contact with animals, PAH, non-arsenic pesticides (carbamates, organophosphates, chlorinated hydrocarbons, triazines and triazoles, phenoxy herbicides, chlorophenols, dibenzodioxin, and dibenzofuran), arsenic pesticides, contact with meat, contact with children, solvents, asbestos, soldering fumes, organic colourants, polychlorinated biphenyls, ethylene oxide, and hair dyes. RESULTS: Although farmers were not at an increased risk of lymphoma as compared with all other occupations, farmers exposed to non-arsenic pesticides were found to be at increased risk of lymphoma (OR = 1.8, 95% CI 1.1 to 2). This increased risk was observed among farmers working exclusively either as crop farmers or as animal farmers (OR = 2.8, 95% CI 1.3 to 5.8). Risk was highest for exposure to non-arsenic pesticides for over nine years (OR = 2.4, 95% CI 1.2 to 2.8). CONCLUSIONS: Long term exposure to non-arsenic pesticides may induce lymphomagenesis among farmers.

Difficulty in elucidating the male role in cervical cancer in Colombia, a high-risk area for the disease.

BACKGROUND: Epidemiologic evidence has been inconclusive in linking men's sexual behavior and genital human papillomaviruses (HPVs) with cervical cancer risk in their sexual partners in areas with a high incidence of cervical cancer. PURPOSE: This study assesses the role of men's sexual behavior and the presence of penile HPV DNA on the risk of their wives' developing cervical neoplasia in an area in Colombia with a high incidence of cervical cancer. METHODS: A total of 210 husbands of women with cervical intraepithelial neoplasia grade III (n = 118) or invasive squamous cell carcinoma of the cervix (n = 92) and a total of 262 husbands of women recruited as control subjects (173 and 89, respectively) were interviewed. Questionnaires included detailed information on sexual behavior. Exfoliated cells were obtained from the glans penis and from the distal urethra of the penis. The specimens were analyzed for HPV DNA by use of a polymerase chain reaction-based assay that included a generic probe and 25 type-specific probes. Serum specimens were collected and analyzed for antibodies to Chlamydia trachomatis, Treponema pallidum, herpes simplex virus type II, and Neisseria gonorrhoeae. RESULTS: Limited education (adjusted odds ratio [OR] = 4.4; 95% confidence interval [CI] = 1.9-9.8; for no schooling versus secondary or higher education) and presence of antibodies to C. trachomatis (adjusted OR = 2.5; 95% CI = 1.5-4.4) in husbands were the only identified risk factors for cervical neoplasia in their wives. The prevalence of HPV DNA in the penis was 25.7% among husbands of case women and 18.9% among husbands of control women (adjusted OR = 1.2; 95% CI = 0.6-2.3). Neither the lifetime number of female sexual partners (adjusted OR = 1.0; 95% CI = 0.4-2.6; for > 50 partners versus one to five) nor the lifetime number of female prostitutes as sexual partners (adjusted OR = 1.2; 95% CI = 0.7-2.0; for > or = 21 prostitutes versus one to five) was associated with the risk of cervical cancer. CONCLUSIONS: Our results are compatible with the hypothesis that in the population of Cali, whose women are at high risk of developing cervical cancer, exposure to HPV among young men is a common occurrence and is mediated by contacts with large numbers of female sexual partners and prostitutes. These widespread sexual practices limit the power of case-control studies to detect significant associations between men's sexual behavior and the cervical cancer risk in their sexual partners. HPV DNA detection in the penis of adult men is a poor reflection of lifetime exposure or of etiologically relevant exposure to HPV. The role of C. trachomatis in cervical carcinogenesis deserves further investigation. IMPLICATIONS: Further research is needed to elucidate the male's role in cervical carcinogenesis in populations at high risk for cervical cancer. HPV DNA prevalence surveys and studies of the natural history of HPV in young men will be of great value.