Alan G. Nyitray

The Epidemiology of Oral HPV Infection among a Multinational Sample of Healthy Men

Background: Oral human papillomavirus type-16 (HPV16) infection is a risk factor for oropharyngeal cancer. We examined oral HPV infection among healthy men. Methods: Oral rinse/gargle specimens and questionnaire data were collected from 1,688 healthy men aged 18 to 74 (median = 31 years), from the United States, Mexico, and Brazil. HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59, and noncarcinogenic HPV types were detected using Roche Linear Array. Results: Oral HPV DNA was detected in 67 of 1,680 (4.0%, 95% CI = 3.1%–5.0%) β-globin–positive specimens; carcinogenic HPVs were detected in 1.3% (95% CI = 0.8%–2.0%; n = 22) and HPV16 was the most commonly detected carcinogenic HPV type (0.6%, 95% CI = 0.2%–1.1%; n = 10). The prevalence of oral HPV infection was similar by country except for HPV55, which had notably higher prevalence in Mexico (3.0%) than Brazil (0%) or the United States (0.2%). Oral HPV prevalence nonsignificantly increased over increasing age categories (Ptrend = 0.096). The strongest predictor of oral HPV was current tobacco use, which increased the odds 2.5-fold (95% CI = 1.4–4.4). Oral sexual behaviors were not associated with oral HPV infection. Conclusions: Oral HPV16 infection was rare in healthy men, especially at younger ages, and was positively associated with current tobacco use. Impact: Oral HPV appears to be about 10-fold less prevalent than infection at genital sites in men (4% vs. ∼40%, respectively). It remains unclear whether this reflects reduced exposure or if the oral region is more resistant to HPV infection compared with anogenital sites. Cancer Epidemiol Biomarkers Prev; 20(1); 172–82. ©2011 AACR.

Age-specific prevalence of and risk factors for anal human papillomavirus (HPV) among men who have sex with women and men who have sex with men: the HPV in men (HIM) study.

BACKGROUND 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. METHODS 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. RESULTS 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 relationship <1 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. CONCLUSIONS 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.

EUROGIN 2014 roadmap: Differences in human papillomavirus infection natural history, transmission and human papillomavirus-related cancer incidence by gender and anatomic site of infection

Human papillomaviruses (HPVs) cause cancer at multiple anatomic sites in men and women, including cervical, oropharyngeal, anal, vulvar and vaginal cancers in women and oropharyngeal, anal and penile cancers in men. In this EUROGIN 2014 roadmap, differences in HPV‐related cancer and infection burden by gender and anatomic site are reviewed. The proportion of cancers attributable to HPV varies by anatomic site, with nearly 100% of cervical, 88% of anal and <50% of lower genital tract and oropharyngeal cancers attributable to HPV, depending on world region and prevalence of tobacco use. Often, mirroring cancer incidence rates, HPV prevalence and infection natural history varies by gender and anatomic site of infection. Oral HPV infection is rare and significantly differs by gender; yet, HPV‐related cancer incidence at this site is several‐fold higher than at either the anal canal or the penile epithelium. HPV seroprevalence is significantly higher among women compared to men, likely explaining the differences in age‐specific HPV prevalence and incidence patterns observed by gender. Correspondingly, among heterosexual partners, HPV transmission appears higher from women to men. More research is needed to characterize HPV natural history at each anatomic site where HPV causes cancer in men and women, information that is critical to inform the basic science of HPV natural history and the development of future infection and cancer prevention efforts.

Prevalence of and Risk Factors for Anal Human Papillomavirus Infection in Heterosexual Men

In US men, the incidence of anal cancer, the primary cause of which is human papillomavirus (HPV) infection, has increased almost 3-fold in 3 decades; however, little is known about the epidemiology of anal HPV infection, especially in heterosexual men. In 2 US cities, behavioral data and anal biological specimens were collected from 253 men who acknowledged having engaged in sexual intercourse with a woman during the preceding year. On the basis of DNA analysis, overall prevalence of anal HPV infection was found to be 24.8% in 222 men who acknowledged having had no prior sexual intercourse with men. Of the men with anal HPV infection, 33.3% had an oncogenic HPV type. Risk factors independently associated with anal HPV were lifetime number of female sex partners and frequency of sex with females during the preceding month. These results suggest that anal HPV infection may be common in heterosexual men.

Six-Month Incidence, Persistence, and Factors Associated With Persistence of Anal Human Papillomavirus in Men: The HPV in Men Study

BACKGROUND Although there are limited numbers of incidence and persistence estimates for anal human papillomavirus (HPV) in women and in men who have sex with men (MSM), there are no such reports for men who have sex with women (MSW). METHODS Genotyping was performed on anal samples from men, aged 18-70, from São Paulo, Brazil; Cuernavaca, Mexico; and Tampa, Florida, who provided specimens at enrollment and the 6-month visit of a 4-year prospective study. Eligibility included no history of genital warts or human immunodeficiency virus. A total of 954 MSW and 156 MSM provided evaluable specimens at both visits. Persistence was defined as type-specific infection at each visit. RESULTS Incident anal infection was common among both MSM and MSW but generally higher for MSM for HPV groups and specific genotypes. A total of 5.1% of MSM and 0.0% of MSW had a persistent HPV-16 infection at the 6-month visit. Cigarette smoking among MSM and age among MSW were associated with persistent infection with any HPV genotype. CONCLUSIONS Although anal HPV infection is commonly acquired by both MSW and MSM, incident events and persistence occurred more often among MSM. Cigarette smoking is a modifiable risk factor that may contribute to HPV persistence among MSM.

Epidemiology and pathology of HPV disease in males

It is currently recognized that besides the significant impact of human papillomavirus (HPV) infection in females, HPV causes substantial disease in men as well. Genital warts are a common manifestation of male infection with HPV. Genital warts are highly infectious and approximately 65% of people who have sex with an infected partner will develop warts themselves. More than 90% of genital warts are caused by non-oncogenic HPV types 6 and 11. In addition, recurrent respiratory papillomatosis is a rare disease most often associated with HPV types 6 and 11. Several cancers of the anogenital tract and upper aero-digestive tract, and their precursor lesions in men are now understood to be caused by infection with sexually transmitted HPV. For example, there is increasing incidence of anal cancer in western countries; however, there are limited data on its primary cause, anal canal HPV infection. Genital HPV infection is very common in men with an ongoing international study estimating a prevalence of 65.2% in asymptomatic males aged 18-70 years. Lifetime number of sexual partners was the most significant risk factor for the acquisition of HPV infection (P<0.05), and circumcision has been associated with reduced detection of HPV infection in men. HPV infections may be less likely to persist in men than in women. In men, the median time to clearance of any HPV infection was 5.9 months, with 75% of infections clearing within 12 months. More data are needed to better understand the natural history of HPV infection. Although the quadrivalent HPV vaccine has been shown to be effective and safe in men, low awareness of HPV in males may be a barrier to its use for the prevention of HPV infection.

Prevalence of and Risk Factors for Anal Human Papillomavirus Infection in Men Who Have Sex with Women: A Cross-National Study

BACKGROUND Although the primary cause of anal cancer is human papillomavirus (HPV) infection in the anal canal, little attention has been paid to the epidemiology of anal HPV infection in men who have sex with women (MSW). METHODS Exfoliated cells from the anal canal of 902 MSW in Brazil (São Paulo), Mexico (Cuernavaca), and the United States (Tampa) were tested for HPV DNA. RESULTS The prevalence of HPV infection in the anal canal (12.0%) was similar among MSW in each city (P=.77), whereas 7.0% had infection with oncogenic types. Men in Tampa had a 4-fold higher prevalence of infection with HPV type 16 (HPV-16) than that among men in São Paulo or Cuernavaca (P<.001). Duration of relationship with a primary sex partner and ever having oral or anal sex with a man was associated with infection with any HPV type and with any oncogenic type, whereas lifetime number of female sex partners was associated with infection with any HPV type. CONCLUSIONS Anal canal HPV infection is commonly found among MSW, and the prevalence of infection with HPV-16 may differ substantially by geography. Men who have a larger lifetime number of female sex partners, who are in a sexual relationship of <1 year in duration, and who have a history of oral or anal sex with men were most likely to have an anal HPV infection.

Health beliefs and attitudes associated with HPV vaccine intention among young gay and bisexual men in the southeastern United States

Gay and bisexual men are at increased risk of anal cancer as a result of human papillomavirus (HPV) infection. Prophylactic vaccination is a potentially effective strategy for preventing anal cancer in this population. The purpose of this study was to identify factors associated with gay and bisexual mens intention to receive HPV vaccine. In the fall of 2010, 179 self-identified gay and bisexual men (mean age 22 years) completed an Internet-based questionnaire assessing beliefs and attitudes toward HPV vaccination. Men were recruited from college-based and Internet venues throughout the southeastern United States. The probability of intent to receive HPV vaccine was modeled using logistic regression. A majority of men (93%) had heard of HPV prior to participation but were generally unaware of the association of HPV with anal, penile, and oral cancers. Only 26% were aware of an HPV vaccine for males. Of the 179 participants, 64 (36%) were likely to be vaccinated. Men most likely to receive HPV vaccine perceived stronger physical and psychological benefits from vaccination and had more positive attitudes toward the vaccine. Conversely, intent to be vaccinated was negatively associated with concern over the financial cost of vaccination. Findings from this study can inform college-based health education programs aimed at increasing vaccine uptake among gay and bisexual men.

The prevalence of genital HPV and factors associated with oncogenic HPV among men having sex with men and men having sex with women and men: The HIM study

Background: Comparative studies of genital human papillomavirus (HPV) among men having sex with men (MSM), men having sex with women and men (MSWM), and men having sex with women (MSW) have not been conducted so far; however, such comparisons may be important for planning prevention strategies like vaccination. Methods: Men, aged 18 to 70 years, were enrolled in a study of genital HPV in São Paulo, Brazil; Cuernavaca, Mexico; and Tampa, FL. Men were classified as MSM (n = 170), MSWM (n = 214), and MSW (n = 3326) based on self-reported sexual behavior. Genotyping for HPV was conducted on cells from the penis and scrotum. Prevalence data were adjusted by country. Factors potentially associated with genital HPV were assessed using multivariable Poisson regression. Results: Genital HPV prevalence was typically higher among MSWM than among MSM or MSW for groups of HPV genotypes including nononcogenic types (51%, 36%, and 42%, respectively), and multiple types (37%, 24%, and 29%, respectively). Age and alcohol consumption in the past month were associated with oncogenic HPV among both MSM and MSWM; however, there were no statistically significant associations between sexual behaviors and genital HPV among MSM or MSWM. Conclusions: Prevalence of genital HPV may be higher among MSWM than among MSW or MSM. Number of female sex partners was associated with genital HPV among MSW, but number of male anal sex partners was not associated with genital HPV among MSM and MSWM.

Prevalent Serum Antibody Is Not a Marker of Immune Protection against Acquisition of Oncogenic HPV16 in Men

In women, naturally induced anti-human papilloma virus (HPV) serum antibodies are a likely marker of host immune protection against subsequent HPV acquisition and progression to precancerous lesions and cancers. However, it is unclear whether the same is the case in men. In this study, we assessed the risk of incident genital infection and 6-month persistent genital infection with HPV16 in relation to baseline serostatus in a cohort of 2,187 men over a 48-month period. Genital swabs were collected every 6 months and tested for HPV presence. Incidence proportions by serostatus were calculated at each study visit to examine whether potential immune protection attenuated over time. Overall, incidence proportions did not differ statistically between baseline seropositive and seronegative men at any study visit or over the follow-up period. The risk of incident and 6-month persistent infection was not associated with baseline serostatus or baseline serum antibody levels in the cohort. Our findings suggest that baseline HPV seropositivity in men is not associated with reduced risk of subsequent HPV16 acquisition. Thus, prevalent serum antibodies induced by prior infection may not be a suitable marker for subsequent immune protection against genital HPV16 acquisition in men.