Factors Associated With Persistence and Clearance of High-Risk Oral Human Papillomavirus (HPV) Among Participants in the HPV Infection in Men (HIM) Study.

BACKGROUND: Human papillomavirus (HPV)-attributable oropharyngeal cancer (HPV-OPC) incidence is increasing in many high-income countries among men. Factors associated with oral HPV persistence, the precursor of HPV-OPC, are unknown. Data from the HPV Infection in Men (HIM) Study, which followed participants >7 years, were utilized to examine rates of persistence and associated factors. METHODS: Oral gargle samples from 3095 HIM study participants were HPV genotyped using the SPF10 PCR-DEIA-LiPA25 assay (DDL Diagnostic Laboratory). Oral HPV persistence for individual and grouped high-risk HPV types among 184 men positive for any high-risk HPV at their oral baseline visit was assessed at 6-month intervals. Factors associated with grouped high-risk HPV/HPV16 persistence were examined using logistic regression. Kaplan-Meier curves were constructed to examine median time to HPV clearance overall, and by selected risk factors. RESULTS: Among the 7 HPV vaccine types, HPV33 had the longest median duration (7.6 months) followed by HPV16 and HPV45 (6.4 months). 10-30% of oral high-risk HPV infections persisted ≥24 months. Six months' persistence of oral high-risk HPV infections was positively associated with age and gingivitis and negatively with lifetime number of sexual partners, while 12 months' persistence was only inversely associated with lifetime number of sexual partners. Oral HPV16 persistence was positively associated with baseline HPV16 L1 antibody status. CONCLUSIONS: Eighteen percent of HPV16 infections persisted beyond 24 months, potentially conferring higher risk of HPV-OPC among these men. Older age appears to be an important factor associated with oral high-risk HPV persistence. More studies among healthy men are required to understand the progression of oral HPV infection to HPV-OPC.

Oral human papillomavirus prevalence and type distribution by country (Brazil, Mexico and the United States) and age among HPV infection in men study participants.

Incidence of human papillomavirus (HPV) attributable oropharyngeal cancers (OPCs) has been increasing globally, especially among men in high-income countries. There is a lack of studies comparing oral HPV prevalence by age and country among healthy men. The purpose of our study was to assess oral HPV prevalence by country and age. Participants of the HPV Infection in Men Study (HIM), a cohort of 3,098 healthy men from São Paulo, Brazil, Cuernavaca, Mexico and Tampa, USA, were studied. Oral HPV prevalence and type distribution were assessed using the SPF10 PCR-DEIA-LiPA25 system. The prevalence of any HPV in Brazil, Mexico and the US was 8.7% (95% CI: 7.1%, 10.4%), 10.0% (95% CI: 8.3%, 12.1%) and 7.6% (95% CI: 5.9%, 9.5%), respectively, while the prevalence of high-risk HPV was 5.3% (95% CI: 4.1%, 6.7%), 7.3% (95% CI: 5.7%, 9.0%) and 5.4% (95% CI: 4.0%, 7.0%), respectively. No significant differences in prevalence of grouped HPV types were observed by country despite significant differences in sexual behaviors. However, the age-specific prevalence of oral HPV differed by country. Brazilian (6.0% [95% CI: 3.4%, 9.7%]) and Mexican (9.2% [95% CI: 5.6%, 14.0%]) participants had peak high-risk HPV prevalence among men aged 41-50 years whereas the US participants had peak prevalence at ages 31-40 years (11.0% [95% CI: 6.4%, 17.3%]). In conclusion, oral HPV prevalence was low with no difference in overall prevalence observed by country. Factors associated with the differences in oral HPV age-patterning by country and sexual orientation require further study.

HPV-6 Molecular Variants Association With the Development of Genital Warts in Men: The HIM Study.

Background: Human papillomavirus type 6 (HPV-6) and HPV-11 are the etiological agents of approximately 90% of genital warts (GWs). The impact of HPV-6 genetic heterogeneity on persistence and progression to GWs remains undetermined. Methods: HPV Infection in Men (HIM) Study participants who had HPV-6 genital swabs and/or GWs preceded by a viable normal genital swab were analyzed. Variants characterization was performed by polymerase chain reaction sequencing and samples classified within lineages (A, B) and sublineages (B1, B2, B3, B4, B5). Country- and age-specific analyses were conducted for individual variants; odds ratios and 95% confidence intervals for the risk of GWs according to HPV-6 variants were calculated. Results: B3 variants were most prevalent. HPV-6 variants distribution differed between countries and case status. HPV-6 B1 variants prevalence was increased in GWs and genital swabs of cases compared to controls. There was difference in B1 and B3 variants detection in GW and the preceding genital swab. We observed significant association of HPV-6 B1 variants detection with GW development. Conclusions: HPV-6 B1 variants are more prevalent in genital swabs that precede GW development, and confer an increased risk for GW. Further research is warranted to understand the possible involvement of B1 variants in the progression to clinically relevant lesions.

Country-specific HPV-related genital disease among men residing in Brazil, Mexico and The United States: The HIM study.

The purpose of this study was to assess whether the incidence of histopathologically confirmed condyloma and penile intraepithelial neoplasia (PeIN) and rates of genital HPV infection progression to these lesions differs by country (Brazil, Mexico and the U.S.). At each visit, lesions were biopsied and were categorized by pathologic diagnoses. The Linear Array genotyping method was used to identify HPV genotypes from genital swabs, while the INNO-LiPA HPV Genotyping Extra method was used for tissue specimens. Age-specific analyses were conducted for lesion incidence by country, with Kaplan-Meier estimation of cumulative incidence. The proportion of HPV infections that progressed to condyloma and PeIN, the median time to lesion development and the incidence rates were estimated by country. When comparing demographic and sexual characteristics across the three countries, sexual orientation (p = 0.008) and lifetime number of female sexual partners (p < 0.0001) were differentially associated with lesion incidence in the three countries. Condyloma incidence in Brazil and the U.S. decreased with age, while incidence remained constant across the lifespan in Mexico. There were no differences by country and age for PeIN incidence. HPV types 6 and 11 were the most common types to progress to condyloma and HPV types 16, 6 and 11 were the most common types to progress to PeIN in all three countries. The continuous risk of condyloma and PeIN across all age groups and countries in this study emphasizes the need to ensure that strong HPV immunity, such as that obtained through vaccination, is maintained across the lifespan of men.

Sequential Acquisition of Anal Human Papillomavirus (HPV) Infection Following Genital Infection Among Men Who Have Sex With Women: The HPV Infection in Men (HIM) Study.

BACKGROUND: The purpose of this study was to assess the risk of sequential acquisition of anal human papillomavirus (HPV) infection following a type-specific genital HPV infection for the 9-valent vaccine HPV types and investigate factors associated with sequential infection among men who have sex with women (MSW). METHODS: Genital and anal specimens were available for 1348 MSW participants, and HPV genotypes were detected using the Roche Linear Array assay. Sequential risk of anal HPV infection was assessed using hazard ratios (HRs) among men with prior genital infection, compared with men with no prior genital infection, in individual HPV type and grouped HPV analyses. RESULTS: In individual analyses, men with prior HPV 16 genital infections had a significantly higher risk of subsequent anal HPV 16 infections (HR, 4.63; 95% confidence interval [CI], 1.41-15.23). In grouped analyses, a significantly higher risk of sequential type-specific anal HPV infections was observed for any of the 9 types (adjusted HR, 2.80; 95% CI, 1.32-5.99), high-risk types (adjusted HR, 2.65; 95% CI, 1.26, 5.55), and low-risk types (adjusted HR, 5.89; 95% CI, 1.29, 27.01). CONCLUSIONS: MSW with prior genital HPV infections had a higher risk of a subsequent type-specific anal infection. The higher risk was not explained by sexual intercourse with female partners. Autoinoculation is a possible mechanism for the observed association.

Distribution and factors associated with salivary secretory leukocyte protease inhibitor concentrations.

OBJECTIVES: This cross-sectional study examined the distribution and correlates of salivary secretory leukocyte protease inhibitor (SLPI) concentrations within a multinational cohort of men. METHODS: Extracellular SLPI was measured in oral gargle cell supernatants of 378 men from three countries using an ELISA-based assay. Risk factor data were collected by a questionnaire. Factors associated with SLPI were assessed using linear and logistic regression for continuous and categorical SLPI, respectively. RESULTS: Among men aged 18-73 years, the median SLPI concentration was 492.0 ng ml-1 (range: 2.3-1919.9). In multivariable modeling, men in Brazil and younger men (18-30 years) were more likely to have higher levels of SLPI [adjusted odds ratio (aOR) 3.84; 95% confidence interval (CI): 1.94-7.59, and aOR 3.84; 95% CI: 1.98-7.43, respectively]. Men with a self-reported sexually transmitted diseases diagnosis in the past 6 months were more likely to have higher SLPI levels (aOR 2.98; 95% CI: 1.1-7.83) and men reporting bleeding/swollen gums were less likely to have higher SLPI (aOR 0.34; 95% CI: 0.15-0.79). Similar results were observed for linear regression models. CONCLUSIONS: Secretory leukocyte protease inhibitor concentrations varied significantly by country and decreased with increasing age. The interaction between SLPI, modifiable factors, and oral infections that influence cancer risk warrants further investigation.

Human papillomavirus virus (HPV) genotype- and age-specific analyses of external genital lesions among men in the HPV Infection in Men (HIM) Study.

BACKGROUND: Human papillomavirus (HPV) causes external genital lesions (EGLs) in men, including condyloma and penile intraepithelial neoplasia (PeIN). We sought to determine the incidence of pathologically confirmed EGLs, by lesion type, among men in different age groups and to evaluate the HPV types that were associated with EGL development. METHODS: HPV Infection in Men (HIM) study participants who contributed ≥2 visits from 2009-2013 were included in the biopsy cohort. Genotyping by an HPV line-probe assay was performed on all pathologically confirmed EGLs. Age-specific analyses were conducted for incident EGLs, with Kaplan-Meier estimation of cumulative incidence. RESULTS: This biopsy cohort included 2754 men (median follow-up duration, 12.4 months [interquartile range, 6.9-19.2 months]). EGLs (n = 377) were pathologically confirmed in 228 men, 198 of whom had incident EGLs. The cumulative incidence of any EGL was highest among men <45 years old and, for condyloma, decreased significantly over time with age. The genotype-specific incidence of EGL varied by pathological diagnoses, with high- and low-risk genotypes found in 15.6% and 73.2% of EGLs, respectively. Condyloma primarily contained HPV 6 or 11. While PeIN lesions primarily contained HPV 16, 1 PeIN III lesion was positive for HPV 6 only. CONCLUSION: Low- and high-risk HPV genotypes contribute to the EGL burden. Men remain susceptible to HPV-related EGLs throughout the life span, making it necessary to ensure the longevity of immune protection against the most common causative HPV genotypes.

Consistent condom use reduces the genital human papillomavirus burden among high-risk men: the HPV infection in men study.

BACKGROUND: Data supporting the efficacy of condoms against human papillomavirus (HPV) infection in males are limited. Therefore, we examined the effect of consistent condom use on genital HPV acquisition and duration of infection. METHODS: A prospective analysis was conducted within the HPV Infection in Men Study, a multinational HPV cohort study. Men who were recently sexually active (n = 3323) were stratified on the basis of sexual risk behaviors and partnerships. Using Cox proportional hazards regression, type-specific incidence of HPV infection and clearance were modeled for each risk group to assess independent associations with condom use. RESULTS: The risk of HPV acquisition was 2-fold lower among men with no steady sex partner who always used condoms, compared with those who never used condoms (hazard ratio, 0.54), after adjustment for country, age, race, education duration, smoking, alcohol, and number of recent sex partners. The probability of clearing an oncogenic HPV infection was 30% higher among nonmonogamous men who always used condoms with nonsteady sex partners, compared with men who never used condoms (hazard ratio, 1.29), after adjustment for country, age, race, education duration, marital status, smoking, alcohol, and number of recent sex partners. No protective effects of condom use were observed among monogamous men. CONCLUSIONS: Condoms should be promoted in combination with HPV vaccination to prevent HPV infection in men.

Prevalence and persistence of HPV-16 molecular variants in the anal canal of men: The HIM study.

BACKGROUND: HPV-16 causes approximately 90% of anal canal (AC) cancers worldwide. This study aimed to evaluate the prevalence and persistence of HPV-16 genetic variants in the AC of men from three different countries (Brazil, Mexico and United States) and to further identify sociodemographic and behavioral factors associated with these infections. METHODS: Participants from the multinational prospective HPV Infection in Men (HIM) Study who had at least one HPV-16 positive AC swab were included. Characterization into HPV-16 genetic variants was successfully performed by PCR-sequencing in 95.6% (217/227) samples and these were classified into HPV-16 lineages and sublineages. RESULTS: We observed higher prevalence of lineage A variants, mainly from A1 sublineage, in all countries. Non-A lineage variants were mostly detected in men from Brazil, where higher diversity of sublineage variants was detected during follow-up. Compare to men detected with Non-A HPV-16 lineage variants, men infected with lineage A reported a higher lifetime number of female sexual partners. Finally, a significantly higher prevalence of Non-A lineage variants was observed among men who have sex with men (MSM) with a transient HPV-16 AC infection (p = 0.033), but no significant differences regarding variants lineages and persistence status were observed when stratified by country, self-reported ethnicity or age. CONCLUSIONS: Our data extend previous reports which indicate that globally HPV-16 variants are unevenly distributed, and contribute further to studies of the natural history of AC HPV infections in men.

Comparison of anal HPV natural history among men by country of residence: Brazil, Mexico, and the United States.

OBJECTIVES: Globally, anal cancer incidence is rare, but is increasing in some world regions. Our objective was to assess differences in anal HPV natural history in three countries. METHODS: Men aged 18-70 years were recruited from the US (n = 634), Mexico (n = 665), and Brazil (n = 731). Anal specimens were collected every six-months. HPV genotyping was assessed by Linear Array. Anal HPV prevalence was compared using the Fisher's exact test. HPV infection incidence rates (IR) and 95% confidence intervals (CI) were calculated. RESULTS: Any anal HPV prevalence was highest among men from Brazil (24%) compared to Mexico (15%) and the US (15%). When stratified by sexual history, the prevalence of any HPV among MSM/MSMW was 43%, 37%, and 45% and 9%, 12%, and 10% for MSW from Brazil, Mexico, and US, respectively. Any HPV incidence was significantly higher among men from Brazil compared to US men (IRR = 2.4, 95% CI = 1.7-3.4) and comparable between men from Mexico and the US (IRR = 1.2, 95% CI = 0.8-1.8). CONCLUSION: Men in Brazil and Mexico often have similar, if not higher incidence of anal HPV compared to men from the U.S., and may benefit from gender neutral HPV vaccine policies.

Concordance of Beta-papillomavirus across anogenital and oral anatomic sites of men: The HIM Study.

We evaluated the concordance between ß-HPVs detected in external genital skin, anal canal, and oral cavity specimens collected simultaneously from 717 men that were participating in the multinational HIM Study. Viral genotyping was performed using the Luminex technology. Species- and type-specific concordance was measured using kappa statistics for agreement. Overall, concordance of ß-HPVs across sites was low and mainly observed among paired genital/anal canal samples. When grouped by species, solely ß-4 HPVs showed moderate concordance in genital/anal pairs (κ = 0.457), which could be attributed to the substantial concordance of HPV-92 in men from Brazil and Mexico (κ > 0.610). ß-HPV type concordance was higher in Mexico, where HPV-19 was consistently concordant in all anatomic site combinations. Our analysis indicates that type-specific concordance across sites is limited to few viral types; however, these infections seem to occur more often than would be expected by chance, suggesting that although rare, there is agreement among sites.

Cutaneous HPV and alpha-mucosal 9-valent HPV sero-status associations.

Seroepidemiology of human papillomaviruses (HPV) among men is poorly understood. We examined the association between seropositivity to cutaneous HPV and 9-valent HPV (9vHPV) types. Six hundred men were randomly selected from the HPV Infection in Men (HIM) Study. Archived serum specimens were tested for antibodies against 9vHPV types [low-risk (6/11) and high-risk (16/18/31/33/45/52/58)], and 14 cutaneous types, including ß-types 5/8/12/14/17/22/23/24/38/47, α-type-27, γ-type-4, µ-type-1, and ν-type-41, using a GST L1-based multiplex serology assay. Risk factor data were collected through questionnaires. Logistic regression was used to evaluate associations between mucosal and cutaneous HPV types. Approximately 21% of men were positive for ≥ 1 cutaneous HPV type, and ≥ 1 nine-valent HPV vaccine type at the same time. Men who were seropositive for any-cutaneous HPV were nearly twice as likely to be seropositive for 9vHPV (adjusted odds ratio (AOR) = 1.97, 95% confidence interval (CI): 1.30-2.99), high-risk (AOR = 1.83; 95% CI: 1.04-3.20), low-risk (AOR = 1.92; 95% CI: 1.16-3.18), and four-valent, 4vHPV, (AOR = 2.01; 95% CI: 1.25-3.21). Type-specific cutaneous HPV seropositivity (types: 8/14/17/23/38/27/4/1) was also positively associated with seropositivity to 9vHPV, high-risk, and low-risk categories. These data indicate that exposure to cutaneous HPV and 9vHPV types is common. Future longitudinal studies are needed to assess the temporality of these associations.

Diversity of beta-papillomavirus at anogenital and oral anatomic sites of men: The HIM Study.

Our goal was to describe prevalence of ß-HPVs at three anatomic sites among 717 men from Brazil, Mexico and US enrolled in the HPV Infection in Men (HIM) Study. ß-HPVs were genotyped using Luminex technology. Overall, 77.7%, 54.3% and 29.3% men were positive for any ß-HPV at the genitals, anal canal, and oral cavity, respectively. Men from US and Brazil were significantly less likely to have ß-HPV at the anal canal than men from Mexico. Older men were more likely to have ß-HPV at the anal canal compared to younger men. Prevalence of ß-HPV at the oral cavity was significantly associated with country of origin and age. Current smokers were significantly less likely to have ß-HPV in the oral cavity than men who never smoked. Lack of associations between ß-HPV and sexual behaviors may suggest other routes of contact such as autoinoculation which need to be explored further.

Cutaneous beta human papillomaviruses and the development of male external genital lesions: A case-control study nested within the HIM Study.

BACKGROUND: Cutaneous human papillomaviruses (HPVs) increase the risk of non-melanoma skin cancer in sun-exposed skin. We examined the role of beta-HPV in the development of male external genital lesions (EGLs), a sun-unexposed site. METHODS: In this nested case-control study (67 men with pathologically-confirmed EGLs and 134 controls), exfoliated cells collected from the surface of lesions and normal genital skin 0, 6, and 12 months preceding EGL development were tested for beta-HPV DNA using a type-specific multiplex genotyping assay. Beta-HPV prevalence was estimated and conditional logistic regression was used to evaluate the association with condyloma, the most common EGL. RESULTS: While beta-HPV prevalence among controls remained stable, the prevalence among cases was lowest on the surface of lesion. Detecting beta-HPV on the normal genital skin was not associated with the presence or development of condyloma. CONCLUSIONS: Cutaneous beta-HPV does not appear to be contributing to pathogenesis in male genital skin.

Genital Human Papillomavirus Infection Progression to External Genital Lesions: The HIM Study.

BACKGROUND: Human papillomavirus (HPV) causes two types of external genital lesions (EGLs) in men: genital warts (condyloma) and penile intraepithelial neoplasia (PeIN). OBJECTIVE: The purpose of this study was to describe genital HPV progression to a histopathologically confirmed HPV-related EGL. DESIGN, SETTING, AND PARTICIPANTS: A prospective analysis nested within the HPV Infection in Men (HIM) study was conducted among 3033 men. At each visit, visually distinct EGLs were biopsied; the biopsy specimens were subjected to pathologic evaluation and categorized by pathologic diagnoses. Genital swabs and biopsies were used to identify HPV types using the Linear Array genotyping method for swabs and INNO-LiPA for biopsy specimens. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: EGL incidence was determined among 1788 HPV-positive men, and cumulative incidence rates at 6, 12, and 24 mo were estimated. The proportion of HPV infections that progressed to EGL was also calculated, along with median time to EGL development. RESULTS AND LIMITATIONS: Among 1788 HPV-positive men, 92 developed an incident EGL during follow-up (9 PeIN and 86 condyloma). During the first 12 mo of follow-up, 16% of men with a genital HPV 6 infection developed an HPV 6-positive condyloma, and 22% of genital HPV 11 infections progressed to an HPV 11-positive condyloma. During the first 12 mo of follow-up, 0.5% of men with a genital HPV 16 infection developed an HPV 16-positive PeIN. Although we expected PeIN to be a rare event, the sample size for PeIN (n=10) limited the types of analyses that could be performed. CONCLUSIONS: Most EGLs develop following infection with HPV 6, 11, or 16, all of which could be prevented with the 4-valent HPV vaccine. PATIENT SUMMARY: In this study, we looked at genital human papillomavirus (HPV) infections that can cause lesions in men. The HPV that we detected within the lesions could be prevented by a vaccine.

An analysis of HPV infection incidence and clearance by genotype and age in men: The HPV Infection in Men (HIM) Study.

OBJECTIVES: Genital HPV infection in men causes benign and cancerous lesions, the incidence of which differs by age. The goal of this work was to comprehensively evaluate incidence and clearance of individual HPV genotypes among men by age group. METHODS: HIV-negative men ages 18-70 with no history of anogenital cancer were recruited for the HPV Infection in Men (HIM) Study. Participants completed clinical exams and questionnaires every six months for up to ~4 years. Genital specimens underwent HPV genotyping, with associations between age and HPV assessed using Cox analyses. RESULTS: 4085 men were followed for a median of 48.6 months (range: 0.3-94.0). Significantly lower HPV incidence rates were observed among the oldest age group (55-70 years) for grouped high-risk (incidence rate ratio [IRR]=0.71), HPV16 (IRR=0.54), grouped low-risk (IRR=0.74), and HPV6 (IRR=0.57) infections compared to men ages 18-24. However, incidence of the grouped 9-valent HPV vaccine types remained constant across the lifespan. Likelihood of HPV6 and HPV16 clearance remained constant until age 54, then increased significantly for men ages 55-70 (adjusted hazard ratio [AHR]=1.92 and 1.65, respectively). CONCLUSIONS: Men remain susceptible to HPV infections throughout their lifespan, highlighting the need for prevention efforts with long-lasting duration.

Diversity of human papillomavirus in the anal canal of men: the HIM Study.

Human papillomavirus (HPV) infections are associated with the development of anogenital lesions in men. There are no reports describing the distribution of non-α HPV types in the anal canal of a sexually diverse group of men. The HPV Infection in Men (HIM) Study is a multicentre study on the natural history of HPV infection in Brazil, Mexico, and the USA. At baseline, 12% of anal canal PCR HPV-positive specimens were not typed by the Roche Linear Array, and were considered to be unclassified. Our goals were to characterize HPVs among these unclassified specimens at baseline, and to assess associations with participant socio-demographic and behavioural characteristics. Unclassified HPVs were typed by sequencing of amplified PGMY09/11 products or cloning of PGMY/GP + nested amplicons followed by sequencing. Further analysis was conducted with FAP primers. Of men with unclassified HPV in the anal canal, most (89.1%) were men who have sex with women. Readable sequences were produced for 62.8% of unclassified specimens, of which 75.2% were characterized HPV types. Eighteen, 26 and three different α-HPV, ß-HPV and γ-HPV types were detected, respectively. α-HPVs were more commonly detected among young men (18-30 years) than among older men (45-70 years), whereas ß-HPVs were more frequent among mid-adult men (31-44 years). ß-HPVs were more common among heterosexual men (85.0%) than among non-heterosexual men. All ß-HPVs detected among non-heterosexual men were ß2-HPV types. The high prevalence of ß-HPV in the anal canal of men who do not report receptive anal sex is suggestive of other forms of transmission that do not involve penile-anal intercourse.

Age-related variation in sexual behaviours among heterosexual men residing in Brazil, Mexico and the USA.

OBJECTIVE: To compare the prevalence of demographic characteristics and sexual behaviours across age groups and to estimate their significance in predicting sexual risk factors by age cohort. METHODS: This cohort study examined sexually transmitted infection (STI) prevalence among heterosexual men in Brazil, Mexico and the USA (N=3047). Participants completed a sexual risk factor questionnaire and were tested for chlamydia, gonorrhoea, syphilis and genital herpes. We examined sexual risk in the study population through a composite measure of STI positivity by age cohort (young: 18-30 years; middle-aged: 31-44 years; older: 45-70 years). Multivariable logistic regression models were used to generate adjusted odds ratios (AORs) and 95% confidence intervals (CIs). RESULTS: We found that STI positivity varied significantly by age group among heterosexual men by a number of covariates. In younger men, having more advanced education had a protective effect (16 years: AOR=0.37, 95% CI 0.15- 0.92), whereas higher numbers of sexual partners elevated the risk for STIs (20-49 partners: AOR=2.06, 95% CI 1.04-4.06; ≥ 50 partners: AOR=4.33, 95% CI 1.74-10.76). Middle-aged men who were black (AOR=1.64, 95% CI 1.10-2.42) and divorced/separated/widowed (AOR=1.91, 95% CI 1.21-3.02) had an increased risk for a positive STI test. Among older men, a younger age at first vaginal sexual encounter (AOR=3.75, 95% CI 1.45-9.74) and a history of exchanging sex for money or drugs heightened STI risk (AOR=2.30, 95% CI 1.0-5.04). CONCLUSIONS: These findings demonstrate that age-related life experiences among heterosexual men influence sexual risk and STI transmission. This topic warrants further investigation to support the development and implementation of targeted interventions that may potentially reduce adverse sexual health outcomes.

Cutaneous human papillomavirus types detected on the surface of male external genital lesions: a case series within the HPV Infection in Men Study.

BACKGROUND: Cutaneous human papillomaviruses (HPVs) may be associated with cutaneous epithelial lesions and non-melanoma skin cancers. No study has systematically evaluated the presence of genus beta [ß]-HPV in male genital skin or external genital lesions (EGLs) OBJECTIVES: To examine cutaneous ß-HPV types detected on the surface of EGLs in men and describe their presence prior to EGL development. STUDY DESIGN: A retrospective case series was conducted among 69 men with pathologically confirmed EGLs (n=72) who participated in the HPV Infection in Men Study. Archived exfoliated cells collected from the surface of each EGL and normal genital skin specimens 6-12 months preceding EGL development were tested for ß-HPV DNA using a type-specific multiplex genotyping assay. RESULTS: ß-HPV DNA was detected on 61.1% of all EGLs, with types 38 (16.7%), 5 (15.3%), and 12 (12.5%) most commonly identified. HPV prevalence differed across pathological diagnoses, with the largest number of ß-HPV types detected on condylomas. Most ß-HPV types were detected on normal genital skin prior to EGL development, though the prevalence was lower on EGLs compared to preceding normal genital skin. CONCLUSIONS: EGLs and the normal genital skin of men harbor a large number of ß-HPV types; however, it appears that ß-HPVs are unrelated to EGL development in men. Despite evidence to support a causal role in skin carcinogenesis at UVR-exposed sites, cutaneous HPV appears unlikely to cause disease at the UVR-unexposed genitals.