Our observation of high prevalence of anal HPV infection among 176 HIV-negative MSM from Latin America and the United States is consistent with past estimates for HIV-negative MSM in Western Europe, Australia, and the United States [8
]. For all HPV outcomes, prevalence among MSM was at least twice as high as among MSW who were recruited from the same source population.
We are aware of 4 studies of anal HPV infection among HIV-negative MSM that have used genotyping assays that detected a comparable number of HPV types as in the current study [8
]. Estimates from these studies for oncogenic HPV prevalence were 26%–73%, whereas HPV-16 prevalence was 9%–27%. Our prevalence estimates in MSM are somewhat lower (27.3% for oncogenic and 6.3% for HPV-16). The MSM in this study were not recruited from gay-identified organizations or events or from HIV-prevention projects, as in other studies in which MSM with increased risk for STDs may have been enrolled; however, one-third of all men enrolled in São Paulo where recruited at an STD clinic that tests for STDs and HIV. It is also possible that different anal sample collection methods, such as different sampling devices, could account for the varying prevalence estimates among studies.
Our estimates among MSW are consistent with our prior research [20
]. However, the estimates are somewhat higher than in 2 other studies [22
], possibly because of the current study's genotyping assays that detect a larger number of genotypes.
Because anal HPV infection is often observed in men who deny receptive anal sex [24
], the mechanism of transport to the anal canal is unclear. Multiple studies have detected mucosal/genital HPV genotypes on fingers [26
], and 1 investigation offered evidence of HPV transmission between hands and anogenital sites [28
]. In the current study, almost 50% of MSW with any anal HPV genotype had dual type-specific infection, at both the anal canal and the genitals, a pattern that also occurred with all common genotypes except HPV-16. We did not ask questions regarding nonpenetrative sexual behaviors, which may have been helpful in understanding anal HPV infection in MSW.
We observed a stable age-specific prevalence of anal HPV in MSW aged 18–70 years, reflecting our previous results in a smaller group of MSW from the same cohort [29
] but in contrast to our prior study of 222 MSW aged 18–40 years [20
In contrast, the current study observed a decreasing age-specific prevalence among MSM, which has been reported elsewhere [30
]; however, these results differ from 2 studies of anal HPV infection in HIV-negative MSM that reported a similar prevalence of anal HPV infection across age groups [8
]. Different source populations may explain the different estimates. For example, Chin-Hong's large study among urban MSM in the United States selected men on the basis of sexual behavior that put them at high risk for HIV infection [9
], whereas MSM in the current study were not targeted for recruitment and, therefore, may have a different pattern of risk for anal HPV infection throughout their lifetimes.
These age-specific HPV infection prevalence trends may result from age-specific sexual behavior. For example, MSM aged 45–70 years reported a mean of .9 new anal sex partners in the prior 3 months, whereas MSM aged <45 years reported 2.7 new partners. Conversely, MSW <45 years of age and >45 years of age reported the same mean of .5 new partners. In addition, when MSM were stratified by number of male anal sex partners (ie, 0 vs. 1 vs. ≥2 partners) in the prior 3 months and by age group, the prevalence of any HPV type at the anal canal decreased with age in every category of number of male anal sex partners (data not shown).
In addition to sexual behavior, immunological processes may mediate age-specific anal HPV infection prevalence in men. Multiple studies have reported increasing age-specific antibody prevalence against HPV type 6, 11, 16, and/or 18 among men [31
] and a positive association between sex with men and HPV seroprevalence in men [32
]. Nevertheless, even if immune responses control some anal infections in older MSM, higher initial prevalence may still leave a substantial burden of infection in older age.
In addition to age, condom use for anal sex and number of sexual partners were associated with anal HPV in MSM. Compared with MSM who reported always using condoms for anal sex, MSM who never used condoms were 6 times more likely to harbor anal canal HPV. In contrast, a previous study reported that risk for anal HPV increased among women who reported condoms being used by male partners; however, that investigation did not ask if condoms were actually used during anal sex [36
]. Our finding that, among MSM, the number of partners was associated with anal HPV is consistent with prior reports [8
Among MSW, number of lifetime sex partners was also associated with anal HPV, which is consistent with our prior 2 reports [20
]. Among MSW we also observed an inverse association between length of sexual relationship and anal HPV. While bivariate analyses among MSM also indicated that longer relationships were protective (data not shown), the association did not remain significant in multivariable analyses. Finally, a history of hepatitis B was strongly associated with both any HPV and oncogenic HPV in MSW. We are not aware of other such reports, although hepatitis has been associated with anal cancer [37
Because we used self–reported data and limited our definition of recent sex to behavior within the prior 3 or 6 months, it is possible that some men were misclassified as either MSW or MSM; however, we have found the CASI instrument to be highly reliable with men in these 3 cities [38
]. Our definition of MSW required that a man had shown a pattern of sexual behavior with women, had reported no recent anal sex with a male, and additionally had reported ≤ 2 male anal partners in his lifetime. We classified a man as MSW even if he acknowledged 1 or 2 male sex partners in his lifetime because sexual experimentation, especially during adolescence, is common in these 3 countries [39
]. To test our definition, we assessed the prevalence of groups of HPV and individual types in MSW who acknowledged no sex with men in their lifetimes. There was no difference in anal HPV prevalence between MSW with 0 lifetime male anal sex partners and MSW with 1 or 2 lifetime male partners (data not shown).
Although all men reported being HIV-negative, we did not test for HIV; therefore, we cannot be certain that all were HIV-negative.
The number of HIV-negative MSM in this study was limited to 176 largely urban men, which, although comparable in size to a number of anal HPV studies in MSM [8
], limits generalization. It possibly also limited our ability to identify statistically significant associations in multivariable analyses. However, a strength of the current study is that both MSM and MSW were recruited from the same source populations which provides a more valid context for comparisons. Finally, although clinicians were trained to deliver the swab directly into the anal canal, it is possible that the swab may have sometimes touched the perianal skin before entry into the anal canal; thus, our estimates may include HPV detected at the perianal region.
Why MSM would have higher β
-globin status than MSW is unclear. One idea is that the practice of receptive anal sex might abrade the mucosal epithelium of the anal canal, allowing better collection of exfoliated cells. However, a subset of MSM were asked about receptive anal sex practices (n
83). Of these there was no difference in β
-globin status among men acknowledging lifetime receptive anal intercourse (β
-globin positivity: 84.5%) and those who said they never had receptive anal intercourse (92.0%, P
.35). With regard to different β
-globin status by clinic site, it is possible that clinicians collecting samples in São Paulo used more pressure on the Dacron swab as it swabbed the anal canal than when the procedure was performed in Cuernavaca or Tampa. While clinicians were all highly trained by an infectious disease physician in this procedure, differential pressure on the Dacron swab by city would be difficult to detect. Nevertheless, since there was little difference in the prevalence of anal HPV by city, we believe different β
-globin results by city should not significantly impact our results.
There were differences in the proportion of men at each clinic site who agreed to an anal sample. For example, more MSW rejected the anal sampling and therefore were excluded the study. If these men also have less risk for anal HPV, then our MSW sample may have been biased toward a population with higher anal HPV prevalence.
Our observation of a higher prevalence of anal HPV in MSM may be due to higher incidence of infection, longer duration, or a combination of these. Further studies are needed to estimate these parameters so that we may better understand how the natural history of anal HPV infection has led to a much higher incidence of anal cancer in MSM.
We believe the current study provides important data for practitioners seeking to lower risk for anal HPV infection in their patients at a time when anal cancer incidence is increasing. Specifically, our data suggest a lower risk for anal HPV infection in MSM who limit their number of male anal sex partners and who always use condoms for anal sex. Secondly, MSW who restrict their number of female sex partners and who remain in relationships for more than 10 years also may lower their risk for anal HPV infection.