Of 1033 participants aged 18–26 years who completed the questionnaire and provided adequate specimens, 111 who reported receiving any HPV vaccine were excluded from this analysis, and the remaining 922 were considered vaccine eligible. Mean and median age was 23 years. Participants represented a variety of races and ethnicities (Table 1). Most identified as male gender (853 [92.5%]), with a sexual orientation of homosexual or gay (643 [69.7%]). Mean age at first sex with any partner was 16 years, and mean number of lifetime sex partners was 37 (median, 15 lifetime sex partners). There were 88 (9.5%) who self-reported their most recent HIV test result as positive. Other results included HIV-negative for 712 (77.2%) and indeterminate for 11 (1.2%); 26 (2.8%) did not get or did not remember their result, and 85 (9.2%) provided no response.

Any type of HPV at the oral site or anal site was detected in 678 participants (73.5%): 661 (71.7%) had any anal HPV, and 87 (9.4%) had any oral HPV, while 70 (7.6%) had any HPV at both sites. Overall, 534 (57.9%) had any high-risk HPV detected in anal or oral specimens. In univariate analysis, prevalence of any HPV and high-risk HPV among vaccine-eligible participants varied significantly (P < .05) by HIV status, sexual orientation, gender identity, and lifetime sex partners but not by race/ethnicity (Table 2). In multivariate analysis, variables associated with any HPV were sexual orientation (P = .0009), HIV status (P = .001), and lifetime number of sex partners (P < .01); for high-risk HPV, associated variables were HIV status (P < .0001) and sexual orientation (P = .006; each analysis was adjusted for city, age group, race/ethnicity, sexual orientation, lifetime number of sex partners, and HIV test result).

The prevalence of oral and anal HPV DNA and seropositivity by HPV type were analyzed according to self-reported HIV status (Table 3). Among 834 participants with negative or unknown HIV status, any HPV was detected in 579 anal specimens (69.4%), including 422 (50.6%) with multiple types. Any HPV was detected in 70 oral specimens (8.4%) from this group. In anal and oral specimens, respectively, high-risk HPV was detected in 438 (52.5%) and 41 (4.9%), HPV 16 was detected in 104 (12.5%) and 9 (1.1%), and at least 1 additional 9vHPV type was detected in 202 (24.2%) and 10 (1.2%). Seropositivity to 4vHPV types was 39.8% for HPV 6, 26.3% for HPV 11, 22.8% for HPV 16, and 19.9% for HPV 18. Combining HPV DNA and serologic results, 525 (62.9%) had evidence of past or current infection with at least 1 4vHPV type, and 255 (30.6%) had evidence of HPV 16; yet only 71 (8.5%) had evidence of all 4vHPV types (Figure 1).

Among 88 HIV-positive participants, any HPV was detected in 82 anal specimens (93.2%), including 80 (90.9%) with multiple types. Any HPV was detected in 17 oral specimens (19.3%) from this group. In anal and oral specimens, respectively, high-risk HPV was detected in 78 (88.6%) and 10 (11.4%), HPV 16 was detected in 32 (36.4%) and 2 (2.3%), and at least 1 additional 9vHPV type was detected in 55 (62.5%) and 3 (3.4%). Seropositivity to 4vHPV types was 64.8% for HPV 6, 50.0% for HPV 11, 51.1% for HPV 16, and 44.3% for HPV 18. Combining HPV DNA and serologic results, 80 (90.9%) had evidence of past or current infection with at least 1 4vHPV type, and 59 (67.1%) had evidence of HPV 16; 26 (29.6%) had evidence of all 4vHPV types (Figure 1).

None of the 922 vaccine-eligible participants had evidence of current anal or oral infection with all 9 of the 9vHPV types or with all 5 additional 9vHPV vaccine types (Table 3).

HPV prevalence was high in this population of young MSM and transgender women. However, despite high numbers of sex partners and other risk factors for HPV infections, most participants in this large study, even those with HIV infection, lacked evidence of current infection or past exposure to all 4vHPV types. Less than one third of those without HIV infection and about two thirds of those with HIV infection had any evidence of past or current infection with HPV 16 alone. In addition, none of the 922 participants had evidence of current infection with all 9vHPV types. Although HPV vaccination is most effective when given before first sexual activity, our findings suggest that many sexually active MSM who are 18–26 years old could benefit from HPV vaccination.

Anal HPV DNA prevalence results from this study are consistent with those of previously published studies conducted among MSM of various ages [2, 11]. In anal specimens, we detected any HPV in 69.4% of specimens from participants without HIV infection and in 93.2% of those with HIV infection. A meta-analysis of HPV prevalence among MSM estimated that the pooled prevalence of any anal HPV was 64.9% among those without HIV infection and 92.6% among those with HIV infection [11]. For high-risk HPV types, pooled prevalence in anal specimens was 37.2% among those without HIV infection and 73.5% among those with HIV infection [11]. Given high baseline prevalence of anal HPV, especially among HIV-positive MSM, HPV vaccine impact among young MSM might be detected earliest among anal specimens as vaccine uptake among eligible young men increases over time.

In oral specimens, we detected any HPV in 8.4% of specimens from participants without HIV infection and in 19.3% of those with HIV infection. These results are in line with previously published data for men and older MSM. A nationally representative study found that the prevalence of oral HPV detection among US men aged 14–69 years was 10.1% [27]. A study of HIV-negative MSM aged 16–40 years found that the oral HPV prevalence was 13.7% for any HPV type, and in a study of HIV-positive MSM, the oral prevalence of any HPV type was initially 17.3% [28, 29]. A larger study of MSM aged ≥18 years (median age, 40 years) found oral prevalences of 8.8% among HIV-negative MSM and 24.8% among HIV-positive MSM for any of 25 HPV types [30]. Although no clinical trial has been conducted specifically evaluating oral HPV-associated disease end points, vaccine efficacy against oral vaccine-type HPV in women was suggested in a post hoc analysis [31]. Postlicensure impact and vaccine effectiveness against oral HPV in men should be explored.

We evaluated seroprevalence as a marker of past HPV exposure and also as a way to assess potential benefit from HPV vaccination. Studies of MSM have consistently reported higher seroprevalences than national studies of US men in general [32], possibly because of higher numbers of sex partners or different routes of exposure as compared to men who have had sex exclusively with women. However, direct comparison of seroprevalence between studies is impeded by the use of different assay formats to measure antibody response to HPV [33]. In this study, about half of participants without HIV infection and three-quarters of those with HIV infection had antibodies to at least 1 4vHPV type. Seroprevalence was highest for HPV 6 followed by HPV 16, similar to the pattern among males in the general population [32]. Antibody positivity to HPV 16 was 51.1% and 22.8% among participants with and without HIV infection, respectively. In the 4vHPV efficacy trial, among MSM with a mean age of 22 years and <5 lifetime sex partners (2.0% with previously undiagnosed HIV infection), seroprevalence at enrollment, determined using a competitive Luminex assay (cLIA), was lower at 22.8% for any 4vHPV types and 7.1% for HPV 16 [6]. However, among MSM enrolled from a sexually transmitted disease clinic with a median age of 40.1 years and a median of 200 lifetime sex partners, the seroprevalence of HPV 16, determined using a fluorescent bead–based ELISA, was 37.1% among HIV-negative MSM and 62.7% among HIV-positive MSM [8, 9]. Since seroconversion after natural infection may be less common in men than women, seropositivity in men might be a less accurate marker of past exposure to HPV [34]. Nevertheless, seroprevalence was high in our study population. Some studies have suggested that antibodies induced by natural infection may not be protective against subsequent HPV [35, 36]; if men with detectable antibody who cleared a previous natural infection are not protected from repeat infections with that type, we might be underestimating the percentage of MSM standing to benefit from vaccination.

Factors associated with HPV infection in our study included lifetime number of sex partners, sexual orientation, and HIV status, consistent with other studies [3, 6–9]. Our study did not identify significant differences in HPV prevalence by race/ethnicity. One analysis of racial differences in HPV incidence and clearance found that Asian/Pacific Islander men had a lower incidence of HPV than white or black men [37]. Additional data are needed on racial disparities in anal HPV and anal cancer prevalence among MSM [38].

Monitoring using self-collected specimens may be a feasible way to assess early vaccine impact in MSM and could also reduce the burden on clinics and clinical staff. The vast majority of self-collected anal swab and oral rinse specimens were adequate for analysis (95.9% and 98.9%, respectively). Methods used in this study may be used to assess HPV prevalence and potential vaccine impact in the future, as more men are vaccinated against HPV. Since HPV vaccine was routinely recommended for US males in late 2011, uptake has risen among males, although remaining low overall: in several large surveys of US MSM aged 18–26 years, self-reported HPV vaccine uptake was 4.9% during 2011 [39], 6.8% at the end of 2011 [40], and 13% by 2013 [41]. Increasing vaccination rates suggest that the vaccine impact in this population could be monitored using baseline data from this study.

Data in this report are subject to several limitations. First, enrollment from clinics serving MSM resulted in a convenience sample that may not be broadly representative of MSM. Also, the 45 transgender women included in this analysis might have unique risk factors worthy of additional investigation; little is known about HPV in this population, and evidence-based clinical recommendations for transgender women are needed. Second, HPV vaccine history and HIV status were self-reported, and medical record review was not conducted to confirm vaccine eligibility, allowing the possibility of misclassification, reporting, or recall bias. Third, since external genital surfaces were not tested, it is possible that some additional current infections might have been missed; however, genital without concurrent anal HPV infection is uncommon among MSM [34].

The United States was one of the first countries to recommend routine HPV vaccination for males. Various countries around the world are considering whether to expand HPV vaccination programs to all boys or to attempt to target young MSM and transgender women despite programmatic difficulties [42–45]. The early impact of HPV vaccination programs, including significant reductions in HPV 16 prevalence and cases of anogenital warts, have been identified in populations where HPV vaccine uptake is <50% and only among females, and cross-protection and herd immunity effects have been detected in populations with higher vaccine uptake among females [46]. Cost-effectiveness modeling suggests that when uptake among girls is low, increasing uptake among girls is still a more cost-effective approach to preventing HPV-associated disease than vaccinating men; however, this strategy would be of limited benefit for MSM [47–50]. Even as more MSM and transgender women are vaccinated, HPV vaccine impact might be challenging to detect if they also have more risk factors for HPV and a higher burden of disease. For these reasons, baseline data on HPV prevalence and seroprevalence among young, vaccine-eligible MSM and transgender women should be useful for planning policy and prevention programs, as well as for monitoring HPV vaccine impact in these at-risk populations.