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Background Human papillomavirus (HPV)-related oropharyngeal cancer (OPC) incidence is increasing among men. Biomarkers that can identify oral HPV16/18 infections likely to persist, the obligate precursor for HPV-OPC, are needed. Methods We assessed the association between oral Epstein-Barr virus (EBV) and oral HPV16/18 persistence among 63 men in the HPV Infection in Men Study who tested positive for HPV16/18 at the baseline visit. Control of oral coinfections, including EBV, could serve as a biomarker of immune competence and the ability to control oral HPV. Results Detection of oral EBV was significantly associated with oral HPV16/18 ≥12-month persistence. Conclusions Detection of oral EBV deserves evaluation as a biomarker for oral HPV persistence and HPV-related OPC.

Background In men, the incidence of human papillomavirus (HPV)–related cancer is rising, but data regarding male HPV infection and seroprevalence are available from only a few countries. Methods This analysis of a global HPV vaccine trial evaluated baseline data from 1399 human immunodeficiency virus–negative heterosexual men (HM) and men who have sex with men (MSM). Key objectives included assessment of HPV prevalence and risk factors for seropositivity to 9-valent HPV (9vHPV) vaccine types (6, 11, 16, 18, 31, 33, 45, 52, and 58), and concordance between seropositivity and prevalent HPV type. Results Overall, 455 of 3463 HM (13.1%) and 228 of 602 MSM (37.9%) were HPV DNA positive for any 9vHPV vaccine type at baseline. Infection prevalence and seroprevalence (≥1 9vHPV vaccine type) were 13.2% and 8.1%, respectively, among 333 HM from Europe, and 37.9% and 29.9%, respectively, among 335 MSM from Europe or North America. Among men with baseline infection, MSM had higher seroprevalence for concordant HPV types (39.5% vs 10.8% in HM). The seropositivity risk (irrespective of baseline infection status) was higher among MSM versus HM (age-adjusted odds ratio, 3.0 [95% confidence interval, 2.4–6.4]). Among MSM, statistically significant seropositivity risk factors included younger age at sexual debut, higher number of receptive anal sex partners, and less frequent condom use. No factors assessed were associated with seropositivity in HM. Conclusions Higher proportions of MSM than HM were HPV DNA positive and seropositive, and concordance between HPV DNA positivity and seropositivity, a potential marker of true infection versus carriage, was higher in MSM. Most MSM and HM were seronegative for all 9vHPV vaccine types, suggesting the potential benefit of catch-up vaccination after sexual debut. Clinical Trials Registration. NCT00090285.

Background Genital wart (GW) incidence is high among men. The percentage and rate at which subsequent GW events occur are understudied. The purpose of this study was to describe the rate of subsequent GWs, associated human papillomavirus (HPV) types, and time to subsequent GW event among unvaccinated men. Methods The study was nested within a multinational prospective HPV natural history study of men aged 18-70 years in the United States, Mexico, and Brazil, examined every 6 months for a median follow-up of 50.4 months. Subsequent GW events were defined as GWs detected after ≥16 weeks of the prior event. Results Forty-four percent of men experienced ≥1 GW following the initial episode. Men with ≥2 subsequent events were at highest risk of continued GW experiences, with as high as 10 postinitial GW events. The incidence rate of each subsequent GW increased with increasing events (incidence of first subsequent event was 13.1 vs 36.6/1000 person-months for the fourth event). The proportion of GWs among HPV-6 and/or -11-positive patients remained constant across events. Approximately 63%-69% were positive for ≥1 of the 9-valent HPV vaccine types. Conclusions These data highlight the high burden of GWs among men across the lifespan and the need for vaccination to prevent multiple GW episodes.

BACKGROUND: Findings from previous studies of cutaneous human papillomavirus (cuHPV) infection and keratinocyte carcinomas have varied due to several factors, including use of different sample types for cuHPV DNA detection. Elucidating the relationship between cuHPV infection in eyebrow hairs (EBHs) and skin swabs (SSWs) is critical for advancing the design of future studies. METHODS: DNA corresponding to 46 β-HPV and 52 γ-HPV types was measured in EBHs and SSWs obtained from 370 individuals undergoing routine skin cancer screening examinations. RESULTS: Prevalence of β-HPV/γ-HPV was 92%/84% and 73%/43% in SSWs and EBHs, respectively, with 71%/39% of patients testing positive for β-HPV/γ-HPV in both sample types. Number of cuHPV types detected and degree of infection were correlated across SSWs and EBHs. When the EBH was positive for a given β-HPV/γ-HPV type, the SSW was positive for that same type 81%/72% of the time. CONCLUSIONS: Testing SSWs captures more cuHPV infection than EBHs, with EBH infections usually representing a subset of SSW infections. The importance of optimizing sensitivity of cuHPV infection detection using SSWs vs specificity using EBHs (or a combination of the 2) will be ascertained in an ongoing cohort study investigating cuHPV associations with subsequent keratinocyte carcinomas.

Background The purpose of this study was to assess genital recurrence of human papillomavirus (HPV) genotypes included in the 9-valent vaccine and to investigate factors associated with recurrence among men in the HPV Infection in Men (HIM) Study. Methods Men were followed every 6 months for a median of 3.7 years. HPV genotypes were detected using Roche linear array. Factors associated with type-specific HPV recurrence (infections occurring after a ≥12-month infection-free period) were assessed. Results In type-specific analyses, 31% of prior prevalent and 20% of prior incident infections recurred. Among prevalent infections, HPV types 52, 45, 16, 58, and 6 and among incident infections, HPV types 58, 52, 18, 16, and 11 had the highest rates of recurrence. New sexual partners (male or female) and frequency of sexual intercourse with female partners were associated with HPV-6, -16, -31, and -58 infection recurrence. In grouped analyses, lifetime and new male sexual partners were associated with recurrence of prior incident infection with any of the 9 HPV types. Conclusions Recurrence of genital HPV infections is relatively common among men and associated with high-risk sexual behavior. Further studies are needed to understand the role of HPV recurrence in the etiology of HPV-associated diseases.

Background Young men who have sex with men (MSM) are at increased risk for human papillomavirus (HPV)-associated disease as a result of HPV infection. Our objective was to characterize the prevalence of high-risk anal HPV infection and factors associated with prevalence in a group of young, primarily black MSM in Houston, Texas. Methods MSM aged 18-29 years were recruited using a respondent-driven sampling method to study HIV and sexually transmitted disease transmission and risk. All engaged in peer-recruitment chains and self-collected anal exfoliated cells. Prevalence ratios assessed factors associated with high-risk HPV and HPV types in the 9-valent vaccine. Results Black race was reported by 87% of men. Slightly over one half (53%) were human immunodeficiency virus (HIV) positive. Approximately 75% of men had at least 1 high-risk HPV type, and 39% of HIV-positive men harbored HPV-16. Analysis that controlled for potential confounders revealed that only HIV infection was associated with high-risk HPV infection. Conclusion Black MSM would benefit from increased HPV vaccination efforts, owing to high rates of HPV infection, increased HPV disease, and low vaccination series completion rates in this population.

Background Little is known about the natural history of human papillomavirus (HPV) infection in male virgins. This study estimated the incidence and clearance of genital HPV infection and the factors associated with these measures among men who denied at baseline ever having penetrative sex. Methods A cohort of 4123 men residing in Brazil, Mexico, and the United States were followed every 6 months for up to 10 visits. Genital exfoliated cells were collected and genotyped for 36 HPV types. Eighty-seven men were classified as virgins and included for analysis. Cox proportional hazards models identified factors associated with the incidence and clearance of genital HPV infection. Results The incidence rates for any HPV infection among virgins who did and those who did not initiate sex during follow-up were 26.2 and 14.6 cases/1000 person-months, respectively. After penetrative sex initiation, 45.5% of men acquired HPV within 24 months. Younger age, current smoking, no recent female sex partners, and prevalent HPV infection were associated with high-risk HPV clearance. Conclusion Virgins who did not initiate sex during follow-up still acquired HPV infection, possibly through nonpenetrative sexual contact. Further prospective cohort studies are needed to better understand factors associated with HPV acquisition and clearance in male virgins and recent nonvirgins.

Background Cutaneous beta human papillomavirus (HPV) infection across cutaneous and mucosal tissues within individuals has not been examined. Methods A subcohort of men (n = 87) participating in the HPV Infection in Men (HIM) study provided eyebrow hairs, forearm skin swabs, genital skin swabs, oral rinse samples, and anal swabs. Beta-HPV DNA in the 5 tissues was detected using a multiplex assay, and site-specific beta-HPV prevalence was examined. Results Any beta-HPV was most prevalent in genital skin (81.6%), followed by forearm skin (64.4%), eyebrow hairs (60.9%), oral mucosa (35.6%), and anal mucosa (33.3%). Most prevalent beta-HPV types included HPV-38 (beta-2) in both genital skin (32.2%) and eyebrow hairs (16.1%), HPV-12 (beta-1) in forearm skin (23%) and oral mucosa (9.2%), and HPV-76 (beta-3) in anal mucosa (14.9%). Concordance of any beta-HPV infection was greater (31.0%) across the 3 keratinized tissue sites (genital skin, eyebrow hairs, forearm skin) than across the 2 mucosal sites (anal and oral mucosa, 6.9%). Conclusions Prevalence of beta-HPV varied by anatomic site of infection. Biological properties of beta-HPV types detected at mucosal sites and their role in disease pathogenesis should be examined.

This study determined the prevalence and risk factors for genital human papillomavirus (HPV) detection among men who deny ever engaging in penetrative sex. A questionnaire was administered to 4123 men from a cohort study of HPV natural history. Genital exfoliated cells were collected and genotyped for 36 HPV types. Eighty-eight men were classified as virgins. Log-binomial regression models identified factors associated with genital HPV detection. The prevalence of any and high-risk HPV types among 88 male virgins was 25.0% and 18.2%, respectively. Age and smoking status were associated with HPV detection. Further studies are needed to better understand the risk for HPV infection among male virgins.

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.

The role of antibody-mediated immunity in preventing newly acquired oral human papillomavirus (HPV) is not well understood. Among 1618 men participating in the HPV Infection in Men (HIM) Study, we evaluated oral rinses for HPV DNA and baseline sera for HPV-6, -11, -16, and -18 L1 antibodies. Thirty percent of men (486) were seropositive for ≥1 HPV type, and 25 men developed incident oral HPV infection (HPV-6 was detected in 7, HPV-11 in 0, HPV-16 in 17, and HPV-18 in 1). Cox models revealed that men with circulating antibodies to HPV-6, -11, -16, or -18 were not less likely to acquire type-specific oral HPV than men without antibodies (hazard ratio for the risk of acquiring HPV-6, -11, -16, or -18, 1.63; 95% confidence interval, .56–4.76).

The incidence of genital warts has been increasing in many western countries since the 1970s [1]. Sexually transmitted human papillomavirus (HPV) infection, usually with types 6 or 11, causes these condylomas, which incur significant morbid effects and substantial economic costs [2, 3]. In addition, genital HPV-16 infection is a major cause of penile squamous cell carcinoma, which, though rare, has either a declining, stable, or increasing incidence in recent decades, depending on country [4–6]. Like cervical cancer, the incidence of penile carcinoma is higher in developing than in developed countries [7]. The burden of some HPV-associated anogenital diseases, but not all, is higher among men having sex with men (MSM) than among men having sex with women (MSW). For example, the incidence of anal cancer, almost all of which is caused by HPV, is many times higher in MSM than in MSW [8]. On the other hand, genital condylomas may have a similar prevalence among these populations [9]. Although anogenital HPV infection is thought to be the most common sexually transmitted infection (STI), there are few published data comparing genital HPV infection among human immunodeficiency virus (HIV)–negative MSM and MSW [10, 11]; however, there is a substantial amount of data from the US STI surveillance system indicating that MSM are more likely than MSW to report a prior diagnosis of certain STIs, such as HIV, syphilis, gonorrhea, human herpesvirus, and hepatitis B [12]. The prevalence of HPV infection in the anal canal is much higher in MSM than in MSW [13], but studies of genital HPV prevalence comparing MSM and MSW have found little difference or even a higher prevalence of genital HPV among MSW than among MSM [10, 14]. Among HIV-infected men, the prevalence of genital HPV is also higher in MSW than in MSM [15]. To our knowledge, however, no prospective studies have examined the incidence and clearance of genital HPV among HIV-negative MSW and MSM. Our objective was to estimate and compare the incidence of genital HPV infections and the duration of incident infections among HIV-negative MSM and MSW. We also examined the incidence of HPV in MSM stratified into men having sex only with men (MSOM) and men having sex with both women and men (MSWM).

Background. Several new polyomaviruses have been discovered in the last decade, including Merkel cell polyomavirus (MCPyV). Little is known about the natural history of the more recently discovered polyomaviruses. We estimated the incidence, prevalence, and persistence of 9 polyomaviruses (MCPyV, BK polyomavirus, KI polyomavirus, JC polyomavirus, WU polyomavirus, Human polyomavirus 6 [HPyV6], HPyV7, HPyV9, and Trichodysplasia spinulosa–associated polyomavirus) and examined factors associated with MCPyV infection in a prospective cohort of 209 men initially enrolled in the HPV Infection in Men (HIM) study. Methods. Participants enrolled at the US site of the HIM study were recruited into a substudy of cutaneous viral infections and followed for a median of 12.6 months. Eyebrow hair and normal skin swab specimens were obtained at each study visit, and the viral DNA load was measured using multiplex polymerase chain reaction. Results. MCPyV infection showed the highest prevalence (65.1% of normal skin swab specimens and 30.6% of eyebrow hair specimens), incidence (81.7 cases per 1000 person-months among normal skin swab specimens, and 24.1 cases per 1000 person-months among eyebrow hair specimens), and persistence (85.8% of normal skin swab specimens and 58.9% of eyebrow hair specimens) among all polyomaviruses examined. Age of >44 years (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.03–4.33) and Hispanic race (OR, 2.64; 95% CI, 1.01–6.88) were associated with an increased prevalence of MCPyV infection in eyebrow hair and normal skin swab specimens, respectively. Conclusion. MCPyV infection is highly prevalent in adults, with age and race being predisposing factors.

Interleukins (ILs) are key regulators of immune response. Genetic variation in IL genes may influence breast cancer risk and mortality given their role in cell growth, angiogenesis and regulation of inflammatory process. We examined 16 IL genes with breast cancer risk and mortality in an admixed population of Hispanic/Native American (NA) (2111 cases and 2597 controls) and non-Hispanic white (NHW) (1481 cases and 1585 controls) women. Adaptive Rank Truncated Product (ARTP) analysis was conducted to determine gene significance and lasso (least absolute shrinkage and selection operator) was used to identify potential gene by gene and gene by lifestyle interactions. The pathway was statistically significant for breast cancer risk overall (P ARTP = 0.0006), for women with low NA ancestry (P(ARTP) = 0.01), for premenopausal women (P(ARTP) = 0.02), for estrogen receptor (ER)+/progesterone receptor (PR)+ tumors (P(ARTP) = 0.03) and ER-/PR- tumors (P(ARTP) = 0.02). Eight of the 16 genes evaluated were associated with breast cancer risk (IL1A, IL1B, IL1RN, IL2, IL2RA, IL4, IL6 and IL10); four genes were associated with breast cancer risk among women with low NA ancestry (IL1B, IL6, IL6R and IL10), two were associated with breast cancer risk among women with high NA ancestry (IL2 and IL2RA) and four genes were associated with premenopausal breast cancer risk (IL1A, IL1B, IL2 and IL3). IL4, IL6R, IL8 and IL17A were associated with breast cancer-specific mortality. We confirmed associations with several functional polymorphisms previously associated with breast cancer risk and provide support that their combined effect influences the carcinogenic process.

BACKGROUND: In this analysis, we examine the incidence and clearance of external genital human papillomavirus (HPV) infection among heterosexual males aged 16-24 years. METHODS: A total of 1732 males aged 16-24 years old in the placebo arm of a quadrivalent HPV vaccine trial were included in this analysis. Participants were enrolled from 18 countries in Africa, the Asia-Pacific region, Europe, Latin America, and North America. Subjects underwent anogenital examinations and sampling of the penis, scrotum, and perineal/perianal regions. RESULTS: The incidence rate of any HPV DNA genotype 6, 11, 16, and/or 18 detection was 9.0 cases per 100 person-years. Rates of HPV DNA detection were highest in men from Africa. Median time to clearance of HPV genotypes 6, 11, 16, and 18 DNA was 6.1, 6.1, 7.7, and 6.2 months, respectively. Median time to clearance of persistently detected HPV 6, 11, 16, and 18 DNA was 6.7, 3.2, 9.2, and 4.7 months, respectively. CONCLUSION: The study results suggest that the acquisition of HPV 6, 11, 16, and/or 18 in males is common and that many of these so-called infections are subsequently cleared, similar to findings for women. Nevertheless, given the high rate of HPV detection among young men, HPV vaccination of males may reduce infection in men and reduce the overall burden of HPV-associated disease in the community.

Presently, there are few validated biomarkers that can predict survival or treatment response for non-small cell lung cancer (NSCLC) and most are based on tumor markers. Biomarkers based on germ line DNA variations represent a valuable complementary strategy, which could have translational implications by subclassifying patients to tailored, patient-specific treatment. We analyzed single nucleotide polymorphisms (SNPs) in 53 inflammation-related genes among 651 NSCLC patients. Multivariable Cox proportional hazard models, adjusted for lung cancer prognostic factors, were used to assess the association of genotypes and haplotypes with overall survival. Four of the top 15 SNPs associated with survival were located in the TNF-receptor superfamily member 10b (TNFRSF10B) gene. The T-allele of the top ranked SNP (rs11785599) was associated with a 41% increased risk of death (95% confidence interval [CI] = 1.16-1.70) and the other three TNFRSF10B SNPs (rs1047275, rs4460370 and rs883429) exhibited a 35% (95% CI = 1.11-1.65), 29% (95% CI = 1.06-1.57) and 24% (95% CI = 0.99-1.54) increased risk of death, respectively. Haplotype analyses revealed that the most common risk haplotype (TCTT) was associated with a 78% (95% CI = 1.25-2.54) increased risk of death compared with the low-risk haplotype (CGCC). When the data were stratified by treatment, the risk haplotypes exhibited statistically significantly increased risk of death among patients who had surgery only and no statistically significant effects among patients who had surgery and adjuvant chemotherapy. These data suggest that possessing one or more risk alleles in TNFRSF10B is associated with an increased risk of death. Validated germ line biomarkers may have potential important clinical implications by optimizing patient-specific treatment.

Hispanic women in the USA have lower breast cancer incidence than non-Hispanic white (NHW) women. Genetic factors may contribute to this difference. Breast cancer genome-wide association studies (GWAS) conducted in women of European or Asian descent have identified multiple risk variants. We tested the association between 10 previously reported single nucleotide polymorphisms (SNPs) and risk of breast cancer in a sample of 4697 Hispanic and 3077 NHW women recruited as part of three population-based case-control studies of breast cancer. We used stratified logistic regression analyses to compare the associations with different genetic variants in NHWs and Hispanics classified by their proportion of Indigenous American (IA) ancestry. Five of 10 SNPs were statistically significantly associated with breast cancer risk. Three of the five significant variants (rs17157903-RELN, rs7696175-TLR1 and rs13387042-2q35) were associated with risk among Hispanics but not in NHWs. The odds ratio (OR) for the heterozygous at 2q35 was 0.75 [95% confidence interval (CI) = 0.50-1.15] for low IA ancestry and 1.38 (95% CI = 1.04-1.82) for high IA ancestry (P interaction 0.02). The ORs for association at RELN were 0.87 (95% CI = 0.59-1.29) and 1.69 (95% CI = 1.04-2.73), respectively (P interaction 0.03). At the TLR1 locus, the ORs for women homozygous for the rare allele were 0.74 (95% CI = 0.42-1.31) and 1.73 (95% CI = 1.19-2.52) (P interaction 0.03). Our results suggest that the proportion of IA ancestry modifies the magnitude and direction of the association of 3 of the 10 previously reported variants. Genetic ancestry should be considered when assessing risk in women of mixed descent and in studies designed to discover causal mutations.

Human papillomavirus (HPV) is the most common sexually transmitted infectious agent worldwide. It can cause or facilitate cervical cancer and other epithelial malignancies [1]. More than 100 HPV types [2] have been identified and are typically classified as low-risk (LR) or high-risk (HR) based on their proclivity to cause cancer. Most HPV types are LR, and only a few, such as HPV 16 and 18, commonly lead to cancer [3]. Distinct molecular differences separate LR and HR HPV types [4], and their course of infection in a host and their transmission between hosts varies. However, the mechanisms linking the evolutionary dynamics of HPV and the sexual activities of human hosts are not well understood. Both HR and LR types of HPV have independently evolved twice in the α genus [2], suggesting convergent evolution in HR and LR forms. This suggests that each type represents a phenotypic strategy that successfully exploits consistent ecological opportunities with human populations. The classic evolutionary trade-off for viruses is virulence versus per-contact transmissibility [5]. More virulent phenotypes produce more virions, increasing the probability of transmission between hosts. However, excessive virion production may either kill the host or trigger a more vigorous immune response. Natural selection often favors intermediate phenotypes, although some ecological circumstances may promote extremes of persistence or virulence [6, 7]. No HPV type is particularly virulent in the sense of directly causing host death. Perhaps because HPV is vulnerable to vigorous immune responses, the majority of HPV infections clear within 1 year [8]. LR types, which produce more virions [9], are typically cleared by the immune system more quickly than HR types [10]. The significance of these differences will become apparent below. We propose that the central trade-off governing HPV phenotypes is virion production, which affects both per-contact transmissibility and the length of infection prior to immune clearance. We hypothesize that this produces 2 divergent strategies. LR HPV types use high virion production to maximize transmissibility per contact while tolerating a shorter persistence time because of immune stimulation. HR HPV types produce fewer virions, which reduces the per-contact transmission rate but permits longer infection time and a greater number of sexual contacts. We find that the relative advantage of each HPV strategy depends on the sexual behaviors in a human population. In our model, HR gains an ecological advantage in a host population, with sexual behavior characterized by monogamous relationships maintained for months to years. LR gains an ecological advantage in a host population in which individuals are serially monogamous, having a high turnover rate of partners. Here, we develop a simple ecological susceptible-infectious-resistant model that includes the sexual behaviors of the host population. We demonstrate that subpopulations will exert different selection pressure on HPV, resulting in speciation into LR and HR phenotypes. In reality of course, most human populations exhibit great diversity of sexual activities and individual behaviors change with time. We find that this promotes ecological coexistence of HPV types. Finally, we examine the dynamics of removing dominant populations from the HR niche through vaccination and the likely evolutionary consequences.

Background. Data on the natural history of human papillomavirus (HPV)–related genital warts (GWs) in men are sparse. We described the distribution of HPV types in incident GWs and estimated GW incidence and time from type-specific incident HPV infections to GW detection in a multinational cohort of men aged 18–70 years. Methods. Participants included 2487 men examined for GWs and tested for HPV every 6 months and followed up for a median of 17.9 months. Samples were taken from 112 men with incident GWs to test for HPV DNA by polymerase chain reaction. Results. Incidence of GWs was 2.35 cases per 1000 person-years, with highest incidence among men aged 18–30 years (3.43 cases per 1000 person-years). HPV 6 (43.8%), HPV 11 (10.7%), and HPV 16 (9.8%) were the genotypes most commonly detected in GWs. The 24-month cumulative incidence of GWs among men with incident HPV 6/11 infections was 14.6% (95% confidence interval [CI], 7.5%–21.1%). Median time to GW detection was 17.1 months (95% CI, 12.4–19.3 months), with shortest time to detection among men with incident infections with HPV 6/11 only (6.2 months; 95% CI, 5.6–24.2 months). Conclusions. HPV 6/11 plays an important role in GW development, with the highest incidence and shortest time to detection among men with incident HPV 6/11 infection.

Anal cancer is the result of infection with an oncogenic human papillomavirus (HPV) type, followed by the development of high-grade anal intraepithelial neoplasia and then invasive cancer. A likely crucial step in anal cancer carcinogenesis is the establishment of a persistent oncogenic HPV infection in anal canal epithelium [1]. Although the annual incidence of anal cancer is rare among men in general (∼1 in 100 000) [2], it is considerably higher among men who have sex with men (MSM), among whom incidence was estimated to be as high as 36 per 100 000 before the human immunodeficiency virus (HIV) epidemic [3, 4]; however, the difference in prevalence of anal canal HPV among MSM and men who have sex with women (MSW) is modest. For example, our cross-sectional studies among HIV-negative men indicate that anal HPV infection is common among MSW: among 1305 MSW, approximately 12% harbored HPV in the anal canal compared with 47% of MSM (including bisexual men) [5]. Thus, whereas prevalence of anal HPV is approximately 4 times higher among MSM, anal cancer incidence among HIV-negative MSM may be approximately 35 times greater. No literature has explained this considerable difference in anal cancer incidence in the context of these populations’ relatively modest difference in anal HPV prevalence. Likewise, there are no published data on behavioral factors associated with anal HPV persistence among HIV-negative MSM and MSW. The identification of modifiable risk factors for anal HPV persistence may be important for anal cancer interventions. Our primary objective was to estimate and compare the incidence and persistence of anal HPV among MSM and MSW. We hypothesized that anal HPV infection was transient among MSW and more persistent among MSM. Our second objective was to assess factors associated with anal HPV persistence.

Background. We examined the baseline prevalence of penile, scrotal, perineal/perianal, and intra-anal human papillomavirus (HPV) infection in human immunodeficiency virus (HIV)‐seronegative men who have sex with men (MSM). Methods. Data were analyzed from 602 MSM aged 16‐27 years with

Background. We examined the baseline prevalence of penile, scrotal, and perineal/perianal human papillomavirus (HPV) in heterosexual men (HM). We also evaluated baseline characteristics of HM to assess factors associated with prevalent HPV detection. Methods. We tested serum samples from 3463 HM aged 16–24 years with 1–5 lifetime female sexual partners for antibodies to HPV 6, 11, 16, and 18. We collected baseline swab specimens for the detection of DNA of HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59 from 3 areas: penile, scrotal, and perineal/perianal. Risk factors for prevalent HPV DNA detection were evaluated. Results. The prevalence of any tested HPV type was 18.7% at the penis, 13.1% at the scrotum, 7.9% at the perineal/perianal region, and 21.0% at any site. Having .3 lifetime female sexual partners had the greatest impact on HPV prevalence: odds ratio (OR) 3.2 (95% confidence interval (CI) 2.1–4.9) for HPV 6, 11, 16, and 18; and OR 4.5 (95% CI 3.3–6.1) for all HPV types tested. HPV DNA detection was highest in Africa. Neither condom usage nor circumcision was associated with HPV DNA prevalence. Conclusion. Genital-HPV DNA detection is common in young, sexually active HM. We found HPV to be most prevalent in African men and least prevalent in men from the Asia-Pacific region. Increased numbers of sexual partners was an important risk factor for HPV DNA prevalence.

An increasing incidence of anal cancer among men suggests a need to better understand anal canal human papillomavirus (HPV) infection among human immunodeficiency virus-negative men.Genotyping for HPV was conducted on cells from the anal canal among men who have sex with women (MSW) and men who have sex with men (MSM), aged 18-70 years, from Brazil, Mexico, and the United States. Factors associated with anal HPV infection were assessed using multivariable logistic regression.The prevalence of any HPV type and oncogenic HPV types did not differ by city. Anal canal HPV prevalence was 12.2% among 1305 MSW and 47.2% among 176 MSM. Among MSW, reporting a lifetime number of ≥ 10 female sex partners, a primary sexual relationship1 year in duration, and a prior hepatitis B diagnosis were independently associated with detection of any anal HPV in multivariable analysis. Among MSM, a younger age, reporting ≥ 2 male anal sex partners in the past 3 months, and never using a condom for anal sex in the past 6 months were independently associated with detection of any anal HPV in multivariable analysis.Number of sex partners was associated with anal HPV infection in both MSW and MSM. Anal HPV infection in men may be mediated by age, duration of sexual relationship, and condom use.

Background. Little is known about the risk factors for cutaneous human papillomavirus (HPV) infection. Methods. To investigate factors associated with cutaneous HPV seropositivity, we conducted a cross-sectional study of 411 patients undergoing routine skin cancer screening examinations. Serum antibodies were measured and evaluated for 36 cutaneous HPV types in the genera alpha, beta, gamma, mu, and nu. Associations of demographic and lifestyle factors with cutaneous HPV seropositivity were estimated using odds ratios and 95% confidence intervals calculated using logistic regression. Results. The seroprevalence of ≥1 cutaneous HPV type was 96% and 90% for men and women, respectively. Seroprevalence was highest for HPV types 4 (46%), 1 (37%), and 8 (31%) in men and for types 4 (47%), 63 (34%), and 1 (33%) in women. Independent associations of demographic and skin cancer risk factors with genus-specific HPV seropositivity differed by sex. For example, white skin, inability to tan, and lifetime residency in Florida were factors associated with genus-specific HPV seropositivity in men. Heavy smoking, sunscreen use, and green eye color were associated with genus-specific HPV seropositivity in women. Conclusions. Seroreactivity to cutaneous HPV types was highly prevalent in our study population. Different risk factors were independently associated with genus-specific cutaneous HPV seropositivity in men and women.

Invasive cervical cancer accounts for 11.6% of all cancers worldwide and is the second most common cancer among women. It is the most common cancer among women living in less developed countries. Although infection with oncogenic-type human papillomaviruses (HPV) is associated with most cases of cervical cancer, HPV infection alone is an insufficient cause of cervical cancer. Research from the last two decades suggests a role for nutrients in the prevention of cervical cancer. However, results from phase III folic acid and β-carotene chemoprevention trials have been negative. Potential reasons for the lack of treatment effect are discussed within the context of cervical carcinogenesis.

BACKGROUND Male circumcision may lower men's risk of human papillomavirus (HPV) infection and reduce transmission to sex partners. Reported associations between circumcision and HPV infection in men have been inconsistent. METHODS Four hundred sixty-three men in 2 US cities were tested at 6 anogenital sites and in semen for 37 types of HPV. Men were eligible if they reported sex with a woman within the past year, no history of genital warts or penile or anal cancer, and no current diagnosis of a sexually transmitted infection. Participants completed a self-administered questionnaire. Circumcision status was assessed by the study clinician. Logistic regression was used to examine associations between circumcision and HPV detection at each site and in semen, with adjustment for potential confounders. RESULTS Seventy-four men (16.0%) were uncircumcised. Adjusted odds ratios (AORs) for any HPV genotype and circumcision were 0.53 (95% confidence interval [CI], 0.28-0.99) for any anatomic site/specimen, 0.17 (95% CI, 0.05-0.56) for the urethra, 0.44 (95% CI, 0.23-0.82) for the glans/corona, and 0.53 (95% CI, 0.28-0.99) for the penile shaft. AORs were

Human papillomavirus (HPV) infection is the necessary etiologic agent for cervical carcinogenesis, with HPV infection in men significantly contributing to infection and subsequent cervical disease in women as well as to disease in men [1–4]. Case-control studies of women with cervical cancer and their husbands have demonstrated that men’s sexual behavior affects women’s risk of cervical neoplasia, even when controlling for female sexual activity. In areas with a high incidence of cervical cancer, men’s sexual behavior is a risk factor for cervical neoplasia [5]. Available information regarding penile HPV infection is primarily derived from 3 sources: (1) studies of husbands of women with cervical cancer [6–9]; (2) cross-sectional studies of select populations, such as patients with sexually transmitted diseases (STDs) and military recruits [10, 11]; and (3) small prospective studies [12, 13] (see [14] for a recent review of the literature). The reported prevalence of HPV infection in men varies widely. Early studies used acetowhitening of the penis as a diagnostic marker for HPV infection and examined men for epithelial lesions [15]. Although HPV is significantly associated with acetowhite penile lesions [16], many other genital conditions are also associated with these lesions [17, 18], resulting in poor specificity for HPV detection. To accurately assess HPV infection in men, molecular techniques must be used. Recent studies using polymerase chain reaction (PCR), a method sensitive enough to detect 10–100 copies of viral DNA, have found HPV detection in men to be as high as in their female counterparts [19]. Most studies of HPV infection in men have sampled penile skin—specifically, the coronal sulcus and glans penis—and the urethra [6–9, 11–13, 20–23]. Many studies combined specimens from the skin and urethra to report HPV DNA prevalence. In 2 studies, urine was collected [21, 24]; however, neither reported HPV DNA results. There is some consensus that sampling the coronal sulcus and glans penis is necessary for assessing HPV status in men because of direct contact with the cervix [14]. There is less consensus regarding urethral sampling, particularly among asymptomatic men. In addition to potentially not yielding informative data, urethral sampling may decrease study participation, particularly in prospective studies that require repetitive sampling of anatomic sites. Several studies have evaluated the scrotum and semen for the presence of HPV DNA [25–38]; however, the majority did not also evaluate the presence of HPV at other anatomic sites [25, 27, 29–31, 34, 36]. As a result, it is unclear whether sampling the scrotum and semen contribute meaningful information to the estimation of HPV prevalence. Twelve studies have attempted to evaluate HPV sampling at multiple anatomic sites [12, 21, 26, 28, 33, 37, 39–44]. The purpose of the present study was to determine the optimal anatomic site(s) for the detection of HPV infection among heterosexual men by assessing HPV DNA in urethral, glans penis/coronal sulcus, penile shaft/prepuce, scrotal, perianal, anal canal, semen, and urine samples.

BACKGROUND Human papillomavirus (HPV) infection is estimated to be the most common sexually transmitted infection; an estimated 6.2 million persons are newly infected every year in the United States. There are limited data on HPV infection in heterosexual men. METHODS We conducted a systematic review of the literature by searching MEDLINE using the terms "human papillomavirus," "HPV," "male," "seroprevalence," and "serology" to retrieve articles published from 1 January 1990 to 1 February 2006. We included studies that had data on population characteristics and that evaluated male genital anatomic sites or specimens for HPV DNA or included assessments of seropositivity to HPV type 6, 11, 16, or 18 in men. We excluded studies that had been conducted only in children or immunocompromised persons (HIV infected, transplant recipients, or elderly). RESULTS We included a total of 40 publications on HPV DNA detection and risk factors for HPV in men; 27 evaluated multiple anatomic sites or specimens, 10 evaluated a single site or specimen, and 3 evaluated risk factors or optimal anatomic sites/specimens for HPV detection. Twelve studies assessed site- or specimen-specific HPV DNA detection. HPV prevalence in men was 1.3%-72.9% in studies in which multiple anatomic sites or specimens were evaluated; 15 (56%) of these studies reported > or =20% HPV prevalence. HPV prevalence varied on the basis of sampling, processing methods, and the anatomic site(s) or specimen(s) sampled. We included 15 publications reporting HPV seroprevalence. Rates of seropositivity depended on the population, HPV type, and methods used. In 9 studies that evaluated both men and women, all but 1 demonstrated that HPV seroprevalence was lower in men than in women. CONCLUSION HPV infection is highly prevalent in sexually active men and can be detected by use of a variety of specimens and methods. There have been few natural-history studies and no transmission studies of HPV in men. The information that we have reviewed may be useful for future natural-history studies and for modeling the potential impact of a prophylactic HPV vaccine.

The association between dietary intake and persistence of type-specific human papillomavirus (HPV) infection, during a 12-month period, among 433 women participating in the Ludwig-McGill HPV Natural History Study was evaluated by use of a nested case-control design. Dietary intake was assessed by a food-frequency questionnaire at the month-4 visit. HPV status was assessed at months 0, 4, 8, and 12 by polymerase chain reaction (MY09/11). Only women who ever tested positive for HPV were included in the present study: 248 had transient HPV infections (1 of 4 positive tests or nonconsecutively positive), and 185 had persistent HPV infections (> or =2 consecutive tests positive for the same HPV type). Risk of type-specific, persistent HPV infection was lower among women reporting intake values of beta-cryptoxanthin and lutein/zeaxanthin in the upper 2 quartiles and intake values of vitamin C in the upper quartile, compared with those reporting intake in the lowest quartile. Consumption of papaya > or =1 time/week was inversely associated with persistent HPV infection.

Human papillomavirus (HPV) is the main etiologic agent of anogenital cancers, including cervical cancer, but little is known about the type-specific prevalence of HPV in men. Participants were men aged 18-70 years attending a sexually transmitted disease clinic. Penile skin swabs were assessed for HPV DNA using polymerase chain reaction with reverse line-blot genotyping. Of 436 swabs collected, 90.1% yielded sufficient DNA for HPV analysis. Men with inadequate swab samples were significantly more likely to be white and circumcised than men with adequate swab samples. The prevalence of HPV was 28.2%. Oncogenic HPV types were found in 12.0% of participants, nononcogenic types were found in 14.8% of participants, multiple types were found in 6.1% of participants, and unknown types were found in 5.9% of participants. The most prevalent subtypes were nononcogenic 6, 53, and 84. HPV positivity was not associated with age. These results indicate that HPV infection among men at high risk is common but that characteristics of male HPV infection may differ from those of female infection.

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.