An expanding, worldwide HIV epidemic is increasingly being documented in men who have sex with men (MSM) and transwomen.1,2 At the same time, those populations are especially vulnerable to sexually transmitted infections (STIs), many of which—including human papillomavirus virus (HPV), gonorrhoea, syphilis, and herpes simplex II virus—are independently associated with HIV aquisition.3–5 Condomless receptive anal intercourse is the main risk behavior for HIV acquisition among MSM and transwomen,6 and for this reason, self-reported sexual behaviors form the backbone of many risk assessment surveys. However, self-report of HIV sexual risk behaviors can be unreliable because of social desirability bias. In clinical settings, fear of discrimination by MSM and transwomen hampers efforts to arrive at an accurate sexual health history.7,8 For these reasons, several tools have been developed to improve the measurement of HIV/STI risks, particularly in a research context, including the use of computer-assisted self-interviewing9 and semen biomarkers.10 However, having a visible marker for HIV risk could be an important, “low-tech” tool that could guide clinicians during assessments of MSM and transwomen in the absence of accurate behavioral data or testing. This is of particular importance for Latino, non–gay-identified MSM (i.e., MSM who self-identify as bisexual or heterosexual) because they are less likely to be targeted in STI/HIV prevention interventions than other MSM.11
Human papillomavirus virus infection specifically in the anal canal among MSM takes place rapidly after sexual debut and persists in approximately 60% of individuals throughout their lifetime.12 Of the most common STIs, HPV is unique in its frequent clinical manifestation of “cauliflower-like” lesions commonly found on the penis, on the scrotum, or in the anus and could serve as a convenient, noninvasive, objective indicator triggering a clinician to consider potential concomittment HIV infection risk. Prevalence of HPV infection ranges from approximately 60% to almost 100% in HIV-uninfected and HIV-infected MSM, respectively.13,14 Although individuals infected with HPV may be more likely to acquire HIV,15,16 the relationship between the clinical manifestation of HPV—anogenital warts—and HIV risk behaviors and acquisition is unknown. Studies have shown that although some risk factors such as number of recent male sex partners and both recent and a lifetime history of receptive anal intercourse are shared risk factors for HPV (but not necessarily genital warts) and HIV infection,12,17,18 an association between anal HPV and unprotected anal intercourse has not always been observed.19–21
In Peru, the estimated HIV prevalence is 12.4% among MSM and 20.8% among transwomen22 compared with 0.40% in the general population.23 Although data on HPV prevalence in these populations are scarce, a recent study of 105 MSM recruited from an urban STI clinic found that 77.1% tested positive for HPV by polymerase chain reaction on anorectal samples.24 In this cross-sectional study, we examined factors associated with visible anogenital warts (overall and by anatomical site), including those that are known to confer increased risk for HIV infection, among HIV-uninfected MSM and transwomen in Lima, Peru.
MATERIALS AND METHODS
Participants and Procedures
Between February 2012 and February 2013, 600 MSM and transwomen were invited to participate in a research study based at Epicentro Salud, a community-based health center in Lima, Peru, that provides STI/HIV services to these populations. In addition to center-based recruitment, participants were also recruited at bars, clubs, and volleyball courts; via social media; and by snowball sampling. The study sought participants both with and without a history of HPV or anogenital warts. Individuals were eligible to participate if they were born anatomically male, were at least 18 years old, reported any anal intercourse with a man during the previous 12 months, were residing in Lima, tested HIV uninfected at enrolment, and had not previously participated in an HIV or HPV vaccine study. HIV status was determined using the Determine HIV-1/2 Combo Ag/Ab test (Alere Inc, Waltham, MA) and confirmed by indirect immunofluorescence assay (in-house test; Peruvian National Institute of Health); individuals testing positive were linked to the national HIV program for free HIV care and treatment. Enrolled participants were first screened for syphilis using the Determine TP test (ALERE Medical Co) and then completed a 20-minute, computer-assisted self-interview. Next, participants underwent a physical examination for circumcision status and the presence of visible anogenital warts by a study clinician who was trained and supervised by an experienced physician from one of Lima’s largest STI clinics. Anogenital warts were treated with 25% podophyllin or liquid nitrogen. Participants with other types of anal lesions or abnormalities were referred to a specialist for follow-up. Participants received US $3 for transportation as well as condoms, lubricant, and a small gift. Institutional review boards at the University of California, Los Angeles, and the Asociación Civil Impacta Salud y Educación in Lima, Peru, reviewed and approved all study materials before implementation.
Data collected included birthplace, education, age, sex of sex partner(s), sexual identity, sex role(s), history of transactional sex (exchange of money or other items of value for sex), age at first anal intercourse, sex and concomitant alcohol use, clinician-observed circumcision status, current STI symptoms, and frequency of condomless anal intercourse.
Univariate analysis was used to examine all variables. χ2 Tests were then used to compare sociodemographic characteristics and sexual risk behaviors among participants with and without visible anogenital warts. Logistic regression was used to assess the unadjusted and adjusted association of all visible anogenital warts with select sample characteristics. The final model for the multivariate logistic regression analysis included only those variables that were significant in the univariate analysis. Lastly, a stratified analysis was conducted to examine the characteristics associated with penile-only and anal-only warts, again using χ2 tests to compare sociodemographic characteristics and sexual risk behaviors with each wart type. All analyses were conducted using Stata Version 12.0 (Stata Corp, College Station, TX).
Sample Characteristics and Presence of Visible Anogenital Warts
Sociodemographic characteristics, sexual risk behaviors, and comparison of sample characteristics with and without visible anogenital warts are presented in Table 1. We screened 756 participants for study participation, of whom 156 (21%) tested HIV positive to arrive at the final sample of 600 HIV-uninfected MSM and transwomen. Of these, nearly half (48%) self-identified as gay, 26% as bisexual, 16% as transwoman, and 10% as heterosexual. Participants reported their sex role as equally insertive (36%) and receptive (36%), 78% reported having anal intercourse for the first time at 19 years or younger, 26% reported 11 or more anal intercourse episodes in the previous 3 months, and 70% reported any condomless anal intercourse with their last sex partner. Approximately 41% of participants reported current STI symptoms, and 18% had a positive syphilis serology indicating current or past infection.
Figure 1 shows the anatomical distribution of visible anogenital warts observed in 223 (37%) of 600 participants. Most of the visible genital warts were either anal only (60%) or penile only (28%). Considering all visible anogenital warts (penis, anal, scrotum), compared with participants without visible anogenital warts, those with visible anogenital warts were significantly more likely to have been born in Lima (60% vs. 51%, P < 0.05); have a higher education level (36% vs. 28%, P < 0.01), be younger than 22 years (37% vs. 25%, P < 0.05), and self-identified as gay (55% vs. 44%, P < 0.01; Table 1). In addition, those with visible anogenital warts were more likely to have sex roles that were equally insertive and receptive (33% vs. 24%, P < 0.01), were less likely to engage in transactional sex (23% vs. 44%, P < 0.001), and self-reported significantly more STI symptoms than participants without visible anogenital warts (53% vs. 34%, P < 0.001). Conversely, participants without visible anogenital warts self-reported consuming alcohol before or during sex significantly more often than those with visible anogenital warts (34% vs. 24%, P < 0.01) and reported more condomless anal intercourse with their last partner (73% vs. 64%, P < 0.05).
Factors Associated With Visible Anogenital Warts
Table 2 presents the unadjusted and adjusted odds ratios (AORs) for factors associated with all visible anogenital warts, limited to those covariates that were significant in Table 1 (birthplace, education, age, sexual identity, sex role, transactional sex, past month sex and alcohol, age first anal intercourse, number of anal intercourse episodes past 3 months, condom used during last episode of anal intercourse, and self-reported STI symptoms). In the adjusted model, presence of visible anogenital warts was higher among participants with a tertiary (nondegree) education compared with a primary or secondary education (AOR, 1.79; 95% confidence interval [CI], 1.07–2.00; P < 0.05), participants who reported having any anal intercourse for the first time at 20+ years of age compared with those younger than 14 years (AOR, 2.80; 95% CI, 1.45–5.38; P < 0.01), and participants who reported current STI symptoms compared with those who did not (AOR, 2.38; 95% CI, 1.61–3.52; P < 0.001). Conversely, the presence of visible anogenital warts was lower among those 22 to 32 and 33+ years of age compared with those younger than 22 years (AORs, 0.41 [95% CI, 0.26–0.63; P < 0.001] and 0.38 [95% CI, 0.19-0.74; P < 0.01], respectively). Presence of visible anogenital warts was also lower among participants who reported their sex role as receptive compared with those who were insertive (AOR, 0.56; 95% CI, 0.34–0.92; P < 0.05). Although several variables in the unadjusted analysis were correlated with the presence of visible anogenital warts, and as important risk factors for HIV acquisition among Peruvian MSM and transwomen, the following variables had a negative relationship to their presence: being a transwoman (OR, 0.37; 95% CI, 0.22–0.64; P < 0.001), engaging in transactional sex (OR, 0.37; 95% CI, 0.25–0.56; P < 0.001), and having more than 10 episodes of anal intercourse in the previous 3 months (OR, 0.36; 95% CI, 0.22–0.61; P < 0.001).
Stratified Analysis by Wart Type
Table 3 shows the stratified analysis for visible penile-only and anal-only warts. Compared with participants without penile warts, those with penile warts were significantly more likely to self-identify as heterosexual, report an only/mostly active sex role, and have an age at first anal intercourse of 20 years or greater (P < 0.001, P < 0.001, and P < 0.01, respectively). Participants with only visible anal warts were significantly more likely than those without anal warts to have a higher education, self-identify as gay, report an only/mostly passive sex role, and report current STI symptoms (P < 0.01, P < 0.01, P < 0.001, and P < 0.001, respectively).
We explored factors associated with visible anogenital warts among 600 HIV-uninfected Peruvian MSM and transwomen, finding that although associated with several sociodemographic characteristics, they were not associated with key HIV-related sexual risk factors (syphilis coinfection, transactional sex, transwoman self-identification, receptive anal intercourse). When considering specific wart types (penile-only or anal-only), self-identified heterosexual, mainly/only active MSM were more likely to have only penile warts, whereas self-identified gay, mainly/only passive MSM were more likely to have only anal warts.
The relationship observed between higher education and higher risk of anogenital warts is consistent with reports on Danish MSM.25 That association suggests that even individuals who may be knowledgeable about HPV and HIV can and do engage in high-risk sexual behaviors.26 However, some authors have also reported higher risk of HPV infection (but not visible anogenital warts) among MSM with lower education levels.27
Contrary to studies reporting an increased presence of HPV in those practicing receptive anal intercourse,24,27 reporting a receptive role during anal intercourse in the present study was associated with a 57% reduction in risk for having anogenital warts compared with only/mostly insertive anal intercourse. This finding is interesting in the context of research identifying the anal canal as an HPV reservoir.19 In addition, self-reported current STI symptoms was highly correlated with increased risk of having visible anogenital warts, consistent with other studies reporting a greater likelihood of HPV infection with clinically diagnosed STIs.24,28
Older age at first episode of anal intercourse was strongly correlated with having visible anogenital warts. This could be due to several factors including improved safe-sex education among younger MSM, lower frequency of anal intercourse acts among those younger than 14 years compared with older MSM, or the development of HPV-specific immunity due to early exposure among those with earlier sexual debut.27 However, evidence for strong, lifelong natural immunity to infection has not been established.29
The univariate analysis findings that engaging in transactional sex and self-identifying as a transwoman were significantly associated with a lower risk of anogenital warts could be related to greater awareness of anogenital warts in these groups.30 Also, the finding that having more than 10 episodes of anal intercourse in the previous 3 months, compared with 3 or fewer episodes, was significantly associated with a 60% decrease in risk of having anogenital warts might be explained by more frequent condom use. Nyitray et al.,17 for example, found that MSM who never used condoms for anal intercourse were 6 times more likely to have anal canal HPV compared with MSM who always used condoms; however, that study did not consider the presence of visible anogenital warts. Nonetheless, because both frequency of anal intercourse and condom use were not significant in the adjusted analysis (and, additionally, condom use itself was limited to only the last episode of anal intercourse) in our study, the association between these 2 variables could not be examined.
Finally, the findings from the stratified analysis, although intuitive (active sex role/penile-only warts and passive sex role/anal-only warts), underscore the HPV burden in MSM who self-identify as heterosexual. Although we cannot determine if the penile warts in the heterosexually identified MSM were from sexual contact with a male or a female, they may be assumed by both clinician and patient to be from heterosexual sex rather than prompting enquiry into potential HIV risks such as anal intercourse with men.
This study used a nonrandom convenience sample of 600 MSM and transwomen meeting the eligibility criteria and may have favored recruiting participants who were more health conscious than “average” MSM or transwomen or those seeking the free anogenital wart treatment in the study and are not generalizable outside this study population. The cross-sectional study design limits the results inasmuch as they only reveal factors associated with, rather than predictors for, visible anogenital warts. In addition, warts inside the anal canal may have gone undetected by the study clinician because anoscopy was not performed. Future directions for this work include biological confirmation of common STIs (gonorrhoea, chlamydia), HPV diagnostic tests, and a prospective, longitudinal cohort study design to measure incident HIV infections and visible anogenital wart predictors.
Because of the intimate nature of questions on sexual behaviors and STI risks, the collection of detailed and accurate data on which to evaluate HIV risk is challenging and a visible marker for HIV risk like visible anogenital warts would be especially useful for clinicians treating non–gay-identified MSM (36% of the study population) presenting with visible penile warts who may be reluctant to disclose same-sex behaviors. Particularly for these non–gay-identified MSM (but for all MSM as well as transwomen), failure to screen for HIV risk in Peru during any health-related encounter represents a missed opportunity to detect or avert incident infections in these populations. Although further research is needed to fully understand the role of HPV on incident HIV infections, the results of this study are sufficient to prompt clinicians treating these populations for visible anogenital warts to consider the possibility of unreported same-sex sexual behaviors and other risk STI/HIV risk factors and provide screening as necessary.
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