Abstract
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.
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.
MATERIALS AND METHODS
Men were recruited in São Paulo, Brazil; Cuernavaca, Mexico; and Tampa, Florida, beginning in June 2005, for the longitudinal HPV in Men (HIM) Study. Inclusion criteria included an age of 18–70 years, no plans to relocate during the 4-year study, no self-reported history of anal cancer or genital warts, and no current sexually transmitted disease (STD) including HIV. Additional details of the study design have been described previously [6].
Men were recruited in São Paulo from the general population through advertisements and from a genitourinary clinic that also tests for HIV and STDs. Men who went to the clinic for STD symptoms or treatment were excluded. In Cuernavaca, men were recruited through a health plan and from factories and the military. Men in Tampa were recruited from a university campus and the general public. MSM were not targeted for recruitment. All participants consented to the study and received a nominal incentive for participation. The study was approved by human subjects committees at each study site.
Study Protocol
Between June 2005 and February 2009, 4063 men enrolled in the HIM Study, and 3395 of these men returned for the 6-month follow-up visit. At each visit, approximately 93% of MSM and approximately 81% of MSW consented to collection of anal canal exfoliated cells. Men who declined anal sampling at either visit were more likely to report being 18–30 years of age, single, never married, MSW, or a Tampa resident (all P < .0001). The first 1763 men who provided an anal sample at both enrollment and the 6-month visit were included in the current analysis.
Men completed an 88-item computer-assisted self-interview (CASI) written in the region’s primary language (Portuguese, Spanish, or English). The CASI elicited information about participant demographics, substance use, and sexual behaviors. After the CASI, a clinician examined the participant for signs of STDs before using three saline-wetted swabs to collect exfoliated skin cells from the penis (ie, coronal sulcus, glans, and ventral and dorsal areas of shaft) and scrotum. Then, using a separate swab, 360° of the anal epithelium was swabbed between the anal os and the anal canal dentate line, after which the swab was placed into standard transport medium and stored at –80°C. The anal canal was not visualized.
HPV Analyses
Samples were analyzed for HPV DNA as described previously [6]. In brief, DNA was extracted using the QIAamp Media MDx Kit (Qiagen). The polymerase chain reaction consensus primer system (PGMY 09/11) was used to amplify a fragment of the HPV L1 gene [7]. HPV genotyping was performed on all samples using DNA probes labeled with biotin to detect 37 HPV types: 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 45, 51–56, 58, 59, 61, 62, 64, 66–73, 81–84, 89, and IS39 [8]. Accuracy and potential contamination were assessed using nontemplate negative controls and CaSki DNA positive controls. Of 1763 men included in the analysis, 1182 (67.0%) were either β-globin or HPV genotype positive at the enrollment and 6-month visit (including 10 men who were β-globin negative but genotype positive). We observed 80.4% and 65.0% β-globin positivity among MSM and MSW, respectively (P < .0001). β-Globin positivity also differed by city: 74.8%, 61.2%, and 65.1% in São Paulo, Cuernavaca, and Tampa, respectively (P < .0001). There was no difference among other variables assessed, for example, age, race, and number of sex partners.
Statistical Analyses
A specimen was considered positive for any HPV if it was positive for ≥1 of 37 genotypes. Specimens were labeled as oncogenic if ≥1 of 13 types were detected (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68 [9]) regardless of the presence of other genotypes. Likewise, specimens were labeled as non-oncogenic if any of the remaining 24 types in the linear array assay were detected, regardless of the presence of oncogenic types; thus, incidence estimates for oncogenic and non-oncogenic groups overlap.
Men were classified as MSW, MSM, men who have sex with women and men (MSWM), and men who do not have sex solely based upon their answers to 17 questions about recent and lifetime penetrative sexual behavior (vaginal, anal, and oral sex). Recent sexual behavior was assessed by questions about behavior in either the previous 3 or 6 months. To minimize the number of contingency tables with sparse data, MSM and MSWM data were combined into 1 group labeled MSM. To classify men as MSW or MSM, greater weight was given to recent sexual behavior and lifetime sexual behavior with multiple partners. For example, if a participant acknowledged any anal or oral sex with other men in the past 6 months or lifetime anal sex with ≥3 men, he was classified as MSM. A participant who acknowledged sex with only women in the past 6 months and <3 lifetime male anal sex partners was classified as MSW. A total of 156 (13.2%) participants were classified as MSM, 954 (80.8%) were classified as MSW, and 71 (6.0%) were classified as men who do not have sex, whereas 1 man provided inadequate information for classification. Analyses were limited to and stratified by MSM and MSW status. A 2-sided Fisher exact or a χ2 test was used to assess differences in characteristics between MSM and MSW and between cities.
Period prevalence was defined as having a specific HPV type at either enrollment or the 6-month visit. Persistent infection was defined as having a specific HPV type at both enrollment and the 6-month visit. An incident infection was defined as the presence of a type-specific infection at the 6-month visit when that type was absent at enrollment. Person time was calculated as the time from specimen collection at enrollment to the date of the 6-month specimen collection. The calculation of 95% confidence intervals (CIs) for the incidence rate was based on the number of incident events and followed a Poisson distribution. Incidence rate ratios and CIs were also calculated using a Poisson distribution.
Men with prevalent HPV were assessed for type-specific clearance, which was defined as a type-specific HPV infection at enrollment that was then undetectable at the 6-month visit. Prevalent infections and clearance events were summed across genotypes for clearance rates of oncogenic, non-oncogenic, and any HPV type.
To assess factors associated with persistent anal HPV, only men with prevalent infections were included in the analysis (ie, men with enrollment infections, which offered the chance to observe persistent infection at the 6-month visit). The sample size for regression analyses was thus reduced to 84 MSM and 125 MSW. Men with a persistent infection for ≥1 of 37 genotypes were defined as cases. Men with no persistence for any genotype were defined as non-cases. Prevalence ratios (PR) and 95% CIs were calculated by Poisson regression using a robust sandwich estimator of the variance [10, 11]. Using directed acyclic graphs [12, 13], potential confounders were identified (ie, city of residence, age, and lifetime number of sex partners) and included in all multivariable modeling, whereas intermediate variables (ie, clinician-diagnosed warts) were excluded from multivariable modeling [14, 15]. Variables with a P value of <.20 on a likelihood ratio test in bivariate analyses were initially included in modeling. Independent risk factors for anal HPV were identified using a backward-elimination method. Variables with a P value of >.05 on a likelihood ratio test were individually removed until a final set of risk factors remained. In initial bivariate analysis, we were more likely to observe persistence among MSM than MSW (PR, 1.86; 95% CI, 1.36–2.54). Thus, subsequent analysis of factors associated with anal HPV persistence was stratified by MSM and MSW status.
In a separate analysis with a subset of men with HPV-16 infection (n = 32), we also assessed the role of multiple infections on persistence for HPV-16 using descriptive statistics.
To assess factors associated with acquisition of anal HPV, only men negative for any HPV type at enrollment were included, which reduced sample size to 72 MSM and 829 MSW. Men who acquired ≥1 HPV genotypes were defined as cases, whereas those not acquiring any genotype were defined as non-cases. Bivariate analysis then proceeded as described previously. Data were analyzed using SAS 9.2 (SAS Institute).
RESULTS
The majority of men classified as MSM (69.9%) were from São Paulo. Although MSW and MSM did not differ by age, differences were observed for other characteristics at enrollment including race and sexual behaviors (all P < .0001; Table 1). Study clinicians diagnosed anogenital warts in 4.5% of MSM and 6.0% of MSW.
Table 1.
Selected Characteristics of Men Who Have Sex With Men and Men Who Have Sex With Women at Enrollment of the HPV in Men (HIM) Study, 2005–2009a
| No. (%) of men | |||
| Characteristic | MSM (n = 156) | MSW (n = 954) | P valueb |
| City of residence | |||
| São Paulo | 109 (69.9) | 307 (32.2) | <.0001 |
| Cuernavaca | 23 (14.7) | 314 (32.9) | |
| Tampa | 24 (15.4) | 333 (34.9) | |
| Age, y | |||
| 18–30 | 68 (43.6) | 405 (42.5) | .07 |
| 31–44 | 70 (44.9) | 372 (39.0) | |
| 45–70 | 18 (11.5) | 177 (18.6) | |
| Median (range) | 32.5 (18–61) | 33.0 (18–70) | |
| Race | |||
| White | 96 (61.5) | 433 (45.4) | <.0001 |
| Black | 29 (18.6) | 146 (15.3) | |
| Mixed/other | 30 (19.2) | 363 (38.1) | |
| Missing data | 1 (0.6) | 12 (1.3) | |
| Ethnicity | |||
| Hispanic | 63 (40.4) | 413 (43.3) | .14 |
| Non-Hispanic | 90 (57.7) | 536 (56.2) | |
| Missing data | 3 (1.9) | 5 (0.5) | |
| Marital status | |||
| Single, never married | 101 (64.7) | 348 (36.5) | <.0001 |
| Married | 26 (16.7) | 376 (39.4) | |
| Cohabitating | 16 (10.3) | 129 (13.5) | |
| Divorced/separated/widowed | 12 (7.7) | 99 (10.4) | |
| Missing data | 1 (0.6) | 2 (0.2) | |
| Duration of relationship with a primary sex partner | |||
| No relationship | 62 (39.7) | 182 (19.1) | <.0001 |
| <1 year | 28 (18.0) | 176 (18.5) | |
| 1–5 years | 31 (19.9) | 212 (22.2) | |
| >5 years | 30 (19.2) | 360 (37.7) | |
| Missing data | 5 (3.2) | 24 (2.5) | |
| Years of school | |||
| <12 | 28 (18.0) | 203 (21.3) | .75 |
| 12 | 37 (23.7) | 235 (24.6) | |
| 13–16 | 79 (50.6) | 446 (46.8) | |
| ≥17 | 12 (7.7) | 68 (7.1) | |
| Missing data | 0 (0.0) | 2 (0.2) | |
| Prepuce present (clinician report) | |||
| Yes | 117 (75.0) | 606 (63.5) | .005 |
| No | 39 (25.0) | 348 (36.5) | |
| Cigarette smoker | |||
| Never | 94 (60.3) | 529 (55.5) | .39 |
| Former | 27 (17.3) | 210 (22.0) | |
| Current | 35 (22.4) | 215 (22.5) | |
| Alcoholic drinks in past month | |||
| 0–30 | 100 (64.1) | 662 (69.4) | .32 |
| 31–60 | 21 (13.5) | 114 (12.0) | |
| >60 | 23 (14.7) | 134 (14.1) | |
| Missing data | 12 (7.7) | 44 (4.6) | |
| Anogenital warts (clinician report) | |||
| Yes | 7 (4.5) | 57 (6.0) | .58 |
| No | 149 (95.5) | 897 (94.0) | |
| Lifetime number of male anal sex partners | |||
| 0–2 | 23 (14.7) | 947 (99.3) | <.0001 |
| 3–9 | 55 (35.3) | 0 (0.0) | |
| ≥10 | 61 (39.1) | 0 (0.0) | |
| Missing data | 17 (10.9) | 7 (0.7) | |
| Median (range) | 6.0 (0–2000) | 0.0 (0–2) | |
| Lifetime number of female sex partners | |||
| 0–2 | 78 (50.0) | 146 (15.3) | <.0001 |
| 3–9 | 32 (20.5) | 337 (35.3) | |
| ≥10 | 31 (19.9) | 422 (44.2) | |
| Missing data | 15 (9.6) | 49 (5.1) | |
| Median (range) | 2.0 (0–100) | 8.0 (0–1000) | |
| Number of male anal sex partners in past 3 months | |||
| 0 | 48 (30.8) | 947 (99.3) | <.0001 |
| 1 | 36 (23.1) | 0 (0.0) | |
| ≥2 | 62 (39.7) | 0 (0.0) | |
| Missing data | 10 (6.4) | 7 (0.7) | |
| Median (range) | 1.0 (0–150) | … | |
| Number of female sex partners in past 6 months | |||
| 0 | 107 (68.6) | 233 (24.4) | <.0001 |
| 1 | 14 (9.0) | 460 (48.2) | |
| ≥2 | 27 (17.3) | 230 (24.1) | |
| Missing data | 8 (5.1) | 31 (3.3) | |
| Median (range) | 0.0 (0–39) | 1.0 (0–15) | |
| Frequency of condom use for anal sex with women or men in past 6 months | |||
| Always | 50 (32.1) | 83 (8.7) | <.0001 |
| Sometimes | 59 (37.8) | 61 (6.4) | |
| Never | 22 (14.1) | 114 (12.0) | |
| No anal sex in past 6 months | 23 (14.7) | 644 (67.5) | |
| Missing data | 2 (1.3) | 52 (5.5) | |
| Frequency of condom use for vaginal sex in past 6 months | |||
| Always | 18 (11.5) | 181 (19.0) | <.0001 |
| Sometimes | 27 (17.3) | 287 (30.1) | |
| Never | 15 (9.6) | 396 (41.5) | |
| No vaginal sex in past 6 months | 90 (57.7) | 82 (8.6) | |
| Missing data | 6 (3.9) | 8 (0.8) | |
Abbreviations: MSM, men who have sex with men; MSW, men who have sex with women.
Sample consists of men who provided evaluable anal samples at both enrollment and the 6-month visit of the HIM Study.
P values are 2-sided and derived from Fisher exact test or χ2 using nonmissing observations.
Prevalence for oncogenic and non-oncogenic types at enrollment did not differ by city among MSM (P = .26 and .70, respectively). Likewise, prevalence for any oncogenic types among MSW at enrollment did not differ significantly by city (P = .14); however, non-oncogenic prevalence did differ (P = .05), with a higher prevalence among MSW from Cuernavaca vs São Paulo or Tampa (11.5%, 6.5%, and 6.9%, respectively; data not shown). After combining the 3 cities, period prevalence for HPV-16 in the anal canal was 10.3% among MSM and 2.7% among MSW (Table 2).
Table 2.
Prevalence, Persistence, and Incidence of Type-Specific Anal Human Papillomavirus Infection Among Men Who Have Sex With Men and Men Who Have Sex With Women in the HPV in Men (HIM) Study, 2005–2009
| MSM (n = 156) |
MSW (n = 954) |
||||||||||||
| Incident anal infections |
Incident anal infections |
||||||||||||
| HPV type | Period prevalence, No. (%)a | Persistent infection, No. (%)b | Men at risk, No. c | Men with infection, No. | Person-months | Incidence rate (95% CI) d | Period prevalence, No. (%)a | Persistent infection, No. (%)b | Men at risk, No. c | Men with infection, No. | Person-months | Incidence rate (95% CI)d | IRR (95% CI) |
| Any HPV | 97 (62.2) | 50 (32.1) | 72 | 13 | 502 | 25.9 (13.8–44.3) | 174 (18.2) | 40 (4.2) | 829 | 49 | 6032 | 8.1 (6.0–10.7) | 3.2 (1.7–5.9) |
| Oncogenic | 65 (41.7) | 25 (16.0) | 107 | 16 | 756 | 21.2 (12.1–34.3) | 86 (9.0) | 15 (1.6) | 892 | 24 | 6472 | 3.7 (2.4–5.5) | 5.7 (3.0–10.7) |
| 16 | 16 (10.3) | 8 (5.1) | 145 | 5 | 1038 | 4.8 (1.6–11.2) | 26 (2.7) | 0 (0.0) | 933 | 5 | 6782 | 0.7 (.2–1.7) | 6.5 (1.9–22.6) |
| 18 | 12 (7.7) | 3 (1.9) | 148 | 4 | 1060 | 3.8 (1.0–9.7) | 8 (0.8) | 0 (0.0) | 952 | 6 | 6916 | 0.9 (.3–1.9) | 4.3 (1.2–15.4) |
| 31 | 4 (2.6) | 0 (0.0) | 153 | 1 | 1095 | 0.9 (.0–5.1) | 4 (0.4) | 2 (0.2) | 951 | 1 | 6909 | 0.1 (.0–.8) | 6.3 (.4–100.8) |
| 33 | 6 (3.9) | 1 (0.6) | 152 | 2 | 1088 | 1.8 (.2–6.6) | 3 (0.3) | 0 (0.0) | 952 | 1 | 6908 | 0.1 (.0–.8) | 12.7 (1.2–140.0) |
| 35 | 7 (4.5) | 3 (1.9) | 150 | 1 | 1067 | 0.9 (.0–5.2) | 1 (0.2) | 0 (0.0) | 953 | 0 | 6922 | 0.0 - | … |
| 39 | 9 (5.8) | 3 (1.9) | 148 | 1 | 1062 | 0.9 (.0–5.2) | 8 (0.8) | 1 (0.1) | 951 | 5 | 6908 | 0.7 (.2–1.7) | 1.3 (.2–11.1) |
| 45 | 8 (5.1) | 2 (1.3) | 151 | 3 | 1076 | 2.8 (.6–8.1) | 5 (0.5) | 2 (0.2) | 950 | 1 | 6904 | 0.1 (.0–.8) | 19.2 (2.0–185.0) |
| 51 | 13 (8.3) | 4 (2.6) | 146 | 3 | 1048 | 2.9 (.6–8.4) | 19 (2.0) | 4 (0.4) | 942 | 7 | 6834 | 1.0 (.4–2.1) | 2.8 (.7–10.8) |
| 52 | 13 (8.3) | 4 (2.6) | 150 | 7 | 1075 | 6.5 (2.6–13.4) | 6 (0.6) | 2 (0.2) | 951 | 3 | 6909 | 0.4 (.1–1.3) | 15.0 (3.9–58.0) |
| 56 | 6 (3.9) | 1 (0.6) | 151 | 1 | 1077 | 0.9 (.0–5.2) | 6 (0.6) | 1 (0.1) | 949 | 1 | 6881 | 0.1 (.0–.8) | 6.4 (.4–102.1) |
| 58 | 7 (4.5) | 2 (1.3) | 152 | 3 | 1089 | 2.8 (.6–8.1) | 7 (0.7) | 1 (0.1) | 950 | 3 | 6904 | 0.4 (.1–1.3) | 6.3 (1.3–31.4) |
| 59 | 11 (7.1) | 1 (0.6) | 151 | 6 | 1065 | 5.6 (2.1–12.3) | 9 (0.9) | 0 (0.0) | 946 | 1 | 6877 | 0.1 (.0–.8) | 38.7 (4.7–321.8) |
| 68 | 5 (3.2) | 2 (1.3) | 154 | 3 | 1101 | 2.7 (.6–8.0) | 4 (0.4) | 3 (0.3) | 951 | 1 | 6910 | 0.1 (.0–.8) | 18.8 (2.0–181.0) |
| Non-oncogenic | 85 (54.5) | 39 (25.0) | 86 | 15 | 615 | 24.4 (13.7–40.2) | 119 (12.5) | 29 (3.0) | 875 | 40 | 6360 | 6.3 (4.5–8.6) | 3.9 (2.1–7.0) |
| 06 | 18 (11.5) | 8 (5.1) | 141 | 3 | 1012 | 3.0 (.6–8.7) | 25 (2.6) | 4 (0.4) | 935 | 6 | 6800 | 0.9 (.3–1.9) | 3.4 (.8–13.4) |
| 11 | 7 (4.5) | 3 (1.9) | 151 | 2 | 1079 | 1.9 (.2–6.7) | 2 (0.2) | 0 (0.0) | 953 | 1 | 6922 | 0.1 (.0–.8) | 12.8 (1.2–141.6) |
| 26 | 1 (0.6) | 0 (0.0) | 155 | 0 | 1109 | 0.0 - | 0 (0.0) | 0 (0.0) | 954 | 0 | 6929 | 0.0 - | … |
| 40 | 3 (1.9) | 0 (0.0) | 153 | 0 | 1095 | 0.0 - | 0 (0.0) | 0 (0.0) | 954 | 0 | 6929 | 0.0 - | … |
| 42 | 5 (3.2) | 0 (0.0) | 155 | 4 | 1109 | 3.6 (1.0–9.2) | 3 (0.3) | 1 (0.1) | 952 | 1 | 6906 | 0.1 (.0–.8) | 24.9 (2.8–222.9) |
| 53 | 18 (11.5) | 5 (3.2) | 143 | 5 | 1018 | 4.9 (1.6–11.5) | 13 (1.4) | 3 (0.3) | 946 | 5 | 6865 | 0.7 (.2–1.7) | 6.7 (2.0–23.3) |
| 54 | 8 (5.1) | 2 (1.3) | 150 | 2 | 1075 | 1.9 (.2–6.7) | 7 (0.7) | 2 (0.2) | 951 | 4 | 6908 | 0.6 (.2–1.5) | 3.2 (.6–17.5) |
| 55e | 5 (3.2) | 2 (1.3) | 153 | 2 | 1092 | 1.8 (.2–6.6) | 3 (0.3) | 1 (0.1) | 953 | 2 | 6923 | 0.3 (.0–1.0) | 6.3 (.9–45.0) |
| 61 | 11 (7.1) | 6 (3.9) | 147 | 2 | 1051 | 1.9 (.2–6.9) | 15 (1.6) | 5 (0.5) | 944 | 5 | 6957 | 0.7 (.2–1.7) | 2.6 (.5–13.5) |
| 62 | 8 (5.1) | 2 (1.3) | 151 | 3 | 1081 | 2.8 (.6–8.1) | 22 (2.3) | 6 (0.6) | 940 | 8 | 6825 | 1.2 (.5–2.3) | 2.4 (.6–8.9) |
| 64e | 1 (0.6) | 0 (0.0) | 156 | 1 | 1115 | 0.9 (.0–5.0) | 0 (0.0) | 0 (0.0) | 954 | 0 | 6929 | 0.0 - | … |
| 66 | 5 (3.2) | 1 (1.3) | 152 | 1 | 1083 | 0.9 (.0–5.1) | 9 (0.9) | 2 (0.2) | 948 | 3 | 6881 | 0.4 (.1–1.3) | 2.1 (.2–20.4) |
| 67 | 3 (1.9) | 0 (0.0) | 154 | 1 | 1101 | 0.9 (.0–5.1) | 1 (0.1) | 0 (0.0) | 953 | 0 | 6921 | 0.0 - | … |
| 69 | 2 (1.3) | 0 (0.0) | 154 | 0 | 1102 | 0.0 - | 0 (0.0) | 0 (0.0) | 954 | 0 | 6929 | 0.0 - | … |
| 70 | 14 (9.0) | 3 (1.9) | 148 | 6 | 1060 | 5.7 (2.1–12.3) | 4 (0.4) | 0 (0.0) | 952 | 2 | 6917 | 0.3 (.0–1.0) | 19.6 (4.0–97.0) |
| 71 | 8 (5.1) | 4 (2.6) | 150 | 2 | 1073 | 1.9 (.2–6.7) | 5 (0.5) | 2 (0.2) | 949 | 0 | 6896 | 0.0 - | … |
| 72 | 7 (4.5) | 0 (0.0) | 155 | 6 | 1108 | 5.4 (2.0–11.8) | 4 (0.4) | 0 (0.0) | 951 | 1 | 6910 | 0.1 (.0–.8) | 37.4 (4.5–310.6) |
| 73 | 16 (10.3) | 5 (3.2) | 146 | 6 | 1042 | 5.8 (2.1–12.5) | 2 (0.2) | 0 (0.0) | 952 | 0 | 6915 | 0.0 - | … |
| 81 | 9 (5.8) | 4 (2.6) | 150 | 3 | 1068 | 2.8 (.6–8.2) | 6 (0.6) | 3 (0.3) | 949 | 1 | 6884 | 0.1 (.0–.8) | 19.3 (2.0–185.8) |
| 82 | 5 (3.2) | 1 (0.6) | 152 | 1 | 1087 | 0.9 (.0–5.1) | 1 (0.1) | 0 (0.0) | 954 | 1 | 6929 | 0.1 (.0–.8) | 6.4 (.4–101.9) |
| 83 | 7 (4.5) | 0 (0.0) | 151 | 2 | 1065 | 1.9 (.2–6.8) | 5 (0.5) | 0 (0.0) | 950 | 1 | 6902 | 0.1 (.0–.8) | 13.0 (1.2–143.0) |
| 84 | 22 (14.1) | 6 (3.9) | 140 | 6 | 1000 | 6.0 (2.2–13.1) | 14 (1.5) | 1 (0.1) | 947 | 7 | 6881 | 1.0 (.4–2.1) | 5.9 (2.0–17.6) |
| 89e | 17 (10.9) | 3 (1.9) | 148 | 9 | 1057 | 8.5 (3.9–16.2) | 14 (1.5) | 3 (0.3) | 943 | 3 | 6848 | 0.4 (.1–1.3) | 19.4 (5.3–71.8) |
| IS39e | 3 (1.9) | 1 (0.6) | 154 | 1 | 1102 | 0.9 (.0–5.1) | 0 (0.0) | 0 (0.0) | 954 | 0 | 6929 | 0.0 - | … |
Abbreviations: CI, confidence interval; HPV, human papillomavirus; IRR, incidence rate ratio; MSM, men who have sex with men; MSW, men who have sex with women.
The number and proportion of men with type-specific infection at either enrollment or the 6-month visit.
The number and proportion of men with type-specific infection at both enrollment and the 6-month visit.
The number of men negative for a specific type at enrollment.
The number of infections per 1000 person-months.
HPV-55 is considered a subtype of HPV-44; HPV-64 is considered a subtype of HPV-34; IS39 is considered a subtype of HPV-82; HPV-89, previously CP6108.
Incidence
Both MSM and MSW were followed for a median of 6.7 months. Incidence rates were higher for MSM than MSW for groups of any HPV type, oncogenic types, and non-oncogenic types, in addition to most individual types. For example, MSM had a rate of acquisition for HPV-16 that was 6.5 times greater (95% CI, 1.9–22.6) than the rate for MSW (Table 2). The 5 highest incidence rates among MSM for oncogenic types were observed for HPV-52, -59, -16, -18, and -51 at 6.5, 5.6, 4.8, 3.8, and 2.9 per 1000 person-months, respectively. The 5 highest incidence rates among MSW for oncogenic types were observed for HPV-51, -18, (tie) -16 and -39, and (tie) -52 and -58 at 1.0, 0.9, 0.7, 0.7, 0.4, and 0.4 per 1000 person-months, respectively.
Persistence and Clearance
A total of 32.1% of MSM and 4.2% of MSW exhibited type-specific persistent anal HPV infection for at least 1 HPV genotype. The proportion of MSM exhibiting persistence of ≥1 oncogenic genotypes was considerably higher than among MSW (16.0% and 1.6%, respectively; P < .0001, Fisher exact test), with persistence highest among MSM for HPV-16 and -6. We detected persistent HPV-16 infection among a total of 5.1% of MSM (Table 2). Among MSW, for any single genotype, no more than 0.6% of MSW were persistent.
A total of 11 MSM had prevalent HPV-16 infection, and 3 (27.2%) of these cleared the infection by the 6-month visit. All 21 MSW with prevalent HPV-16 cleared the infection by the 6-month visit (Table 3). Type-specific clearance of any HPV type for MSM and MSW was more comparable (57.1% and 70.9%, respectively).
Table 3.
Type-Specific Clearance of Human Papillomavirus Infectionsa in Men Who Have Sex With Men and Men Who Have Sex With Women in the HPV in Men (HIM) Study, 2005–2009
| MSM infections |
MSW infections |
|||
| Prevalent | Cleared | Prevalent | Cleared | |
| No. | No. (%) | No. | No. (%) | |
| Any HPV | 212 | 121 (57.1) | 175 | 124 (70.9) |
| Oncogenicb | 77 | 43 (55.8) | 71 | 55 (77.5) |
| 16 | 11 | 3 (27.2) | 21 | 21 (100.0) |
| 18 | 8 | 5 (62.5) | 2 | 2 (100.0) |
| 51 | 10 | 6 (60.0) | 12 | 8 (66.7) |
| 56 | 5 | 4 (80.0) | 5 | 4 (80.0) |
| 59 | 5 | 4 (80.0) | 8 | 8 (100.0) |
| Non-oncogenicc | 135 | 78 (57.8) | 104 | 69 (66.3) |
| 06 | 15 | 7 (46.7) | 19 | 15 (78.9) |
| 11 | 5 | 2 (40.0) | 1 | 1 (100.0) |
| 53 | 13 | 8 (61.5) | 8 | 5 (62.5) |
| 61 | 9 | 3 (33.3) | 10 | 5 (50.0) |
| 62 | 5 | 3 (60.0) | 14 | 8 (57.1) |
| 71 | 6 | 2 (33.3) | 5 | 3 (60.0) |
| 81 | 6 | 2 (33.3) | 5 | 2 (40.0) |
| 84 | 16 | 10 (62.5) | 7 | 6 (85.7) |
| 89d | 8 | 5 (62.5) | 11 | 8 (72.7) |
Abbreviations: HPV, human papillomavirus; MSM, men who have sex with men; MSW, men who have sex with women.
The unit of analysis for clearance was infections instead of individuals.
Oncogenic types 31, 33, 35, 39, 45, 52, 58, and 68 are not shown because there were <5 prevalent infections among both MSM and MSW.
Non-oncogenic types 26, 40, 42, 54, 55, 64, 66, 67, 69, 70, 72, 73, 82, 83, and IS39 are not shown because there were <5 prevalent infections among both MSM and MSW.
HPV-89, previously CP6108.
Risk Factors
In bivariate analyses for MSM, city of residence and cigarette smoking were associated with persistence of any HPV type. Among MSW, persistence was associated with age and a self-reported history of gonorrhea and inversely associated with duration of relationship with primary sex partner (Table 4). In bivariate analysis for factors associated with HPV acquisition, no factors were significant among MSM, although sparse data resulted in frequent unstable estimates. Among MSW, city of residence, race, and cigarette smoking status were associated with HPV acquisition (data not shown).
Table 4.
Factors Associated With Persistent Anal Canal Human Papillomavirus Infections in Men Who Have Sex With Men and Men Who Have Sex With Women in São Paulo, Cuernavaca, and Tampa in the HPV in Men (HIM) Study: Bivariate Analysesa,b
| Factor | MSM (n = 84) |
MSW (n = 125) |
||
| No. with persistent infection (%) | PR (95% CI) | No. with persistent infection (%) | PR (95% CI) | |
| City of residence | ||||
| São Paulo | 55 (58.2) | 1.33 (.73–2.49) | 29 (34.5) | 1.35 (.66–2.76) |
| Cuernavaca | 13 (84.6) | 1.93 (1.06–3.53) | 53 (35.9) | 1.40 (.75–2.62) |
| Tampa | 16 (43.8) | Ref | 43 (25.6) | Ref |
| Age, y | ||||
| 18–30 | 45 (64.4) | Ref | 53 (22.6) | Ref |
| 31–44 | 33 (51.2) | 0.80 (.54–1.19) | 47 (31.9) | 1.41 (.74–2.70) |
| 45–70 | 6 (66.7) | 1.03 (.56–1.90) | 25 (52.0) | 2.30 (1.23–4.29) |
| Trendc | P = .53 | P = .01 | ||
| Race | ||||
| White | 52 (57.7) | Ref | 49 (26.5) | Ref |
| Black | 14 (50.0) | 0.87 (.49–1.54) | 12 (41.7) | 1.57 (.69–3.55) |
| Mixed/other | 17 (70.6) | 1.22 (.83–1.80) | 61 (34.4) | 1.30 (.73–2.32) |
| Ethnicity | ||||
| Hispanic | 37 (67.6) | Ref | 65 (35.4) | Ref |
| Non–Hispanic | 46 (52.2) | 0.77 (.54–1.10) | 59 (28.8) | 0.81 (.48–1.37) |
| Marital status | ||||
| Single, never married | 62 (56.5) | Ref | 46 (23.9) | Ref |
| Married | 9 (55.6) | 0.98 (.53–1.84) | 40 (32.5) | 1.36 (.69–2.69) |
| Cohabitating | 8 (75.0) | 1.33 (.84–2.10) | 20 (35.0) | 1.46 (.67–3.22) |
| Divorced/sep/widow | 5 (80.0) | u.e. | 19 (47.4) | 1.98 (.98–3.99) |
| Duration of relationship with primary sex partner | ||||
| No primary sex partner | 36 (58.3) | 1.05 (.55–2.00) | 25 (28.0) | 0.64 (.32–1.30) |
| <1 year | 19 (68.4) | 1.23 (.64–2.38) | 24 (16.7) | 0.38 (.15–.99) |
| 1–5 years | 20 (55.0) | 0.99 (.49–2.01) | 27 (29.6) | 0.68 (.35–1.32) |
| >5 years | 9 (55.6) | Reference | 48 (43.8) | Reference |
| Trendc | P = .80 | P = .06 | ||
| Years of school | ||||
| <12 | 12 (66.7) | Ref | 31 (38.7) | Ref |
| 12 | 23 (52.2) | 0.78 (.45–1.37) | 26 (34.6) | 0.89 (.45–1.78) |
| 13–16 | 42 (59.5) | 0.89 (.56–1.43) | 58 (27.6) | 0.71 (.39–1.31) |
| ≥17 | 7 (71.4) | 1.07 (.58–1.98) | 10 (30.0) | 0.78 (.27–2.20) |
| Trendc | P = .83 | P = .31 | ||
| Cigarette smoker | ||||
| Never | 52 (48.1) | Ref | 58 (31.0) | Ref |
| Former | 10 (60.0) | 1.25 (.70–2.23) | 28 (32.1) | 1.04 (.53–2.01) |
| Current | 22 (86.4) | 1.80 (1.29–2.49) | 39 (33.3) | 1.07 (.60–1.93) |
| Trendc | P = .002 | P = .81 | ||
| Pack-years of smoking cigarettes | ||||
| Never smoked | 52 (48.1) | Ref | 58 (31.0) | Ref |
| <2.0 | 11 (81.8) | 1.70 (1.14–2.53) | 26 (19.2) | 0.62 (.26–1.49) |
| ≥2.0 | 21 (76.2) | 1.58 (1.09–2.29) | 36 (44.4) | 1.43 (.84–2.43) |
| Trendc | P = .01 | P = .25 | ||
| Alcohol drinks in past month | ||||
| 0–30 | 53 (54.7) | Ref | 91 (35.2) | Ref |
| 31–60 | 15 (73.3) | 1.34 (.91–1.98) | 10 (20.0) | 0.57 (.16–2.03) |
| >60 | 13 (53.9) | 0.98 (0.56–1.72) | 19 (26.3) | 0.75 (.34–1.67) |
| Trendc | P = .72 | P = .35 | ||
| Prepuce present (clinician report) | ||||
| Yes | 61 (55.7) | 0.80 (.56–1.14) | 86 (33.7) | 1.20 (.67–2.14) |
| No | 23 (69.6) | Ref | 39 (28.2) | Ref |
| History of gonorrhea diagnosis | ||||
| Yes | 15 (66.7) | 1.18 (.78–1.78) | 13 (53.9) | 1.81 (1.02–3.23) |
| No | 67 (56.7) | Ref | 111 (29.7) | Ref |
| Lifetime number of male anal sex partners | ||||
| 0–2 | 7 (71.4) | Ref | 125 (32.0) | Ref |
| 3–9 | 28 (53.6) | 0.75 (.42–1.34) | 0 - | u.e. |
| ≥10 | 38 (63.2) | 0.88 (.52–1.50) | 0 - | u.e. |
| Trendc | P = .91 | u.e. | ||
| Lifetime number of female sex partners | ||||
| 0–2 | 49 (53.1) | Ref | 14 (35.7) | Ref |
| 3–9 | 19 (68.4) | 1.29 (.86–1.93) | 41 (29.3) | .82 (.35–1.91) |
| ≥10 | 10 (70.0) | 1.32 (.81–2.14) | 63 (34.9) | .98 (.45–2.13) |
| Trendc | P = .20 | P = .82 | ||
| Number of male anal sex partners in past 3 months | ||||
| 0 | 14 (57.1) | Ref | 125 (32.0) | Ref |
| 1 | 21 (57.1) | 1.00 (.56–1.80) | 0 - | u.e. |
| ≥2 | 46 (60.9) | 1.07 (.64–1.77) | 0 - | u.e. |
| Trendc | P = .76 | u.e. | ||
| Number of female sex partners in past 6 months | ||||
| 0 | 65 (60.0) | Ref | 35 (37.1) | Ref |
| 1 | 6 (50.0) | 0.83 (.37–1.90) | 50 (28.0) | 0.75 (.41–1.40) |
| ≥2 | 8 (62.5) | 1.04 (.59–1.85) | 36 (33.3) | 0.90 (.48–1.69) |
| Trendc | P = .97 | P = .74 | ||
| Number of new male anal sex partners in past 3 months | ||||
| 0 | 26 (53.9) | Ref | 125 (32.0) | Ref |
| 1 | 21 (52.4) | 0.97 (.57–1.67) | 0 - | u.e. |
| ≥2 | 31 (67.7) | 1.26 (.82–1.94) | 0 - | u.e. |
| Trendc | P = .27 | u.e. | ||
| Number of new female sex partners in past 6 months | ||||
| 0 | 67 (59.7) | Ref | 76 (30.3) | Ref |
| 1 | 6 (50.0) | 0.84 (.37–1.91) | 34 (35.3) | 1.17 (.66–2.06) |
| ≥2 | 5 (60.0) | u.e. | 11 (36.4) | 1.20 (.51–2.82) |
| Trendc | P = .85 | P = .56 | ||
| Frequency of condom use for anal sex with women or men in past 6 months | ||||
| Always | 22 (50.0) | Ref | 9 (33.3) | Ref |
| Sometimes | 43 (62.8) | 1.26 (.78–2.02) | 10 (20.0) | 0.60 (.13–2.82) |
| Never | 12 (66.7) | 1.33 (.75–2.38) | 11 (18.2) | 0.55 (.11–2.59) |
| No anal sex in past 6 months | 5 (60.0) | u.e. | 84 (34.5) | 1.04 (.39–2.73) |
Bold text identifies point estimates and 95% confidence intervals that did not include unity.
Abbreviations: CI, confidence interval; MSM, men who have sex with men; MSW, men who have sex with women; PR, prevalence ratio; u.e., unstable point estimate.
A persistent case was defined as a man with type-specific infection at enrollment and the 6-month visit for ≥1 of 37 genotypes. Those with no persistence for any genotype were defined as non-cases.
Only men with prevalent infection were included in analyses.
Cochran–Armitage test for trend.
In multivariate analyses (Table 5), only current cigarette smoking was associated with persistence of anal HPV among MSM (in comparison to never smokers: PR, 1.73 [95% CI, 1.19–2.50] for current smokers). Among MSW, only age was associated with persistence (in comparison to men aged 18–30 years: PR, 2.47 [95% CI, 1.28–4.75] for men aged 45–70 years).
Table 5.
Factors Associated With Persistent Anal Canal Human Papillomavirus Infections in Men Who Have Sex With Men and Men Who Have Sex With Women in São Paulo, Cuernavaca, and Tampa in the HPV in Men Study: Multivariable Analysesab
| Factor | MSMc | MSWd |
| PR (95% CI) | PR (95% CI) | |
| Age, y | ||
| 18–30 | Ref | Ref |
| 31–44 | 0.80 (.56–1.14) | 1.37 (.69–2.70) |
| 45–70 | 0.67 (.26–1.77) | 2.47 (1.28–4.75) |
| Cigarette smoking | ||
| Never | Ref | Ref |
| Former | 1.33 (.71–2.46) | 0.93 (.46–1.86) |
| Current | 1.73 (1.19–2.50) | 1.02 (.58–1.77) |
Bold text indicates point estimates and 95% confidence intervals that do not include unity.
Abbreviations: CI, confidence interval; MSM, men having sex with men; MSW, men having sex with women; PR, prevalence ratio.
A persistent case was defined as a man with infection at enrollment and the 6-month visit for ≥1 of 37 genotypes. Those with no persistence for any genotype were defined as non-cases.
Only men with prevalent infection were included in analyses.
Only cigarette smoking remained statistically significant in the model. Prevalence ratios for cigarette smoking are adjusted by potential confounders city of residence, age, and lifetime number of male anal sex partners. Age is included only for comparison purposes.
Only age remained statistically significant in the model. Prevalence ratios for age are adjusted by potential confounders city of residence and lifetime number of female sex partners. Cigarette smoking is included only for comparison purposes; its prevalence ratios are adjusted by residence, age, and lifetime number of female sex partners.
Of 11 MSM with HPV-16 at enrollment, 10 were coinfected with other genotypes. Of these 10 men, HPV-16 was detected again at the 6-month visit in 8 men. Of 21 MSW with HPV-16 at enrollment, only 2 were coinfected with other genotypes, and none of these men had persistent HPV-16 infection (data not shown).
DISCUSSION
To our knowledge, these are the first prospective data available for anal HPV among MSW. Compared with MSM, we consistently observed a lower period prevalence, incidence, and persistence of anal HPV among MSW. For example, we observed 16.0% of MSM to have persistent oncogenic infection compared with 1.6% of MSW. Likewise, 5.1% of MSM had persistent HPV-16, the genotype responsible for the large majority of anal cancer incidence. In contrast, none of 21 MSW with prevalent HPV-16 retained the infection at the 6-month clinical visit. Reflecting the uniquely important role of HPV-16 in cervical cancer [16], HPV-16 in the anal canal among MSM was one of the most common and least likely to clear genotypes. In contrast, for most other genotypes, ≥50% of infections cleared by the 6-month clinical visit. For MSM, these data underscore the potential benefit of vaccines that prevent HPV-16 infection.
These findings support our original hypothesis that anal HPV would be transient among MSW and more persistent among MSM. We believe that these data also help explain the disparate anal cancer incidence rates among MSM and MSW and their more modest differences in anal HPV prevalence. For example, period prevalence for the oncogenic group of genotypes among MSM was 4.6-fold higher than among MSW, whereas the proportion of MSM with persistent oncogenic infection was 10-fold higher than among MSW. Although anal HPV is commonly detected among MSW, it appears to be rare for oncogenic HPV infection to persist among MSW.
Compared to MSW, the rate of acquisition of anal HPV infection was generally several-fold higher among MSM. High anal HPV incidence and persistence among MSM have been reported elsewhere. Both Critchlow et al [17] and Chin-Hong et al [18] reported an annual cumulative incidence for any anal HPV of approximately 0.40 among HIV-negative MSM. Regarding persistence, Chin-Hong et al [18] also observed 74% of MSM with incident HPV-16 infection to have persistent HPV-16 infection over 2 consecutive clinical visits spaced 6 months apart. HPV-6 was reported to have been persistent among 70% of MSM with incident HPV-6 [18]. We observed 73% of MSM with prevalent HPV-16 infection to be persistent, whereas 53% of men with HPV-6 were persistent.
Cigarette smoking was associated with persistence of anal infection among MSM but not MSW after controlling for potential confounding by age, city of residence, and number of sexual partners. In addition to a recognized role in cervical carcinogenesis [19], cigarette smoking is an established risk factor for anal cancer among men and women [20, 21]. It has also been associated with anal squamous intraepithelial lesions [22, 23] and slowed clearance of anal HPV infection among women [24]. The association between smoking and anal carcinogenesis is plausible, given the potential for immune dysregulation and increased DNA mutations in anogenital epithelium [25, 26]. In bivariate analysis, we observed an association between smoking and persistence in MSW with ≥2.0 pack-years of smoking; however, the association could have been due to chance.
Age was independently associated with anal HPV persistence among MSW. Like other cancers, risk for anal cancer increases with age [27]; however, we did not find age to be associated with anal HPV persistence among MSM. Among women, Shvetsov et al [24] found no association between age and clearance of anal HPV.
Our prior studies have found strong associations between number of sexual partners among both MSM and MSW and anal HPV prevalence; however, in the current study, persistence of anal HPV was not associated with number of partners. Our observation that anal HPV-16 persistence only occurred in the context of multiple anal HPV infections deserves additional study; however, the sparse data preclude drawing conclusions.
The number of MSM in this study was limited to 156 largely urban men; thus, the sample size, in addition to the participants’ self-selection, limits generalizability of these findings. Sample size also contributed to unstable estimates for factors associated with acquisition. 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. Also, because we used self-reported data and weighted more recent sex behavior to classify MSM and MSW, it is possible that some men were misclassified; however, we have found the CASI instrument used in the current study to be highly reliable with men in these 3 cities [28]. In addition, weighting more recent behavior may be appropriate given that HPV is usually a transient infection.
MSM were more likely to be β-globin positive than MSW. We explored the possibility that receptive anal sex might abrade anal canal epithelium and thus allow better collection of exfoliated cells; however, among a subset of 83 MSM asked about receptive anal sex practices, there was no difference in β-globin positivity among men acknowledging lifetime receptive anal intercourse (77.9%) and those who reported no receptive anal intercourse (73.3%; P = .70). It is also possible that fecal matter may include polymerase chain reaction inhibitors. If more fecal matter was present among MSW than MSM, it may have lowered our sensitivity for detection of MSW β-globin [29, 30]. With regard to higher β-globin positivity in São Paulo, it is possible that clinicians collecting samples there (versus Cuernavaca or Tampa) used more pressure on the swab as it swept the anal canal. Although clinicians were all trained by an infectious disease physician in this procedure, differential pressure on the swab among clinicans would be difficult to detect. Nevertheless, because prevalence of anal HPV by city did not differ except for the non-oncogenic HPV group among MSW, we believe the β-globin results should not unduly impact our overall conclusions.
Differences between men included and excluded from the study, including the optional nature of the anal sampling, could have biased some estimates. For example, 81% of MSW accepted the anal sampling versus 93% of MSM. Even so, genital HPV prevalence among MSW included and excluded from the study was not substantially different (50.7% and 51.3%, respectively; P = .79, Fisher exact test).
It is also possible that our study underestimates incidence because the date of clinic visit was used as the date of the incident event. Second, we cannot rule out that persistent infection reflects clearance of an HPV type and then reinfection with that type between clinic visits. Likewise, we cannot rule out that incident detection of HPV is actually a reappearance of an existing infection [31]. 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.
Data in the current study begin to illustrate starkly differing natural histories of anal HPV among MSM and MSW that helps to explain the disparate anal cancer incidence among these groups observed in Western countries. However, the sample size used to evaluate persistence, especially HPV-16 persistence, was quite small in this study. Larger studies with extended follow-up of anal HPV infection and clinical disease will help elucidate the causes of increased anal cancer incidence among MSM.
Finally, cigarette smoking is a modifiable risk factor that likely contributes to anal disease among MSM [23, 32, 33]. Our finding of increased anal HPV persistence among MSM who are current smokers, together with increased prevalence of smoking among MSM compared with MSW in the United States and some developing countries [34, 35], corroborates the importance of smoking cessation interventions among MSM. Also modifiable are risk factors associated with prevalent anal HPV that we have observed in previous research with MSM: a higher number of anal sex partners and lack of condom use for anal sex [5].
Notes
Acknowledgments.
The authors give special thanks to the men who provided personal information and biological samples for the study. Thanks to the HIM Study Team in São Paulo, Cuernavaca, and Tampa, including Lenice Galan, Elimar Gomes, Elisa Brito, Filomena Cernicchiaro, Rubens Matsuo, Vera Souza, Ricardo Cintra, Ricardo Cunha, Birgit Fietzek, Raquel Hessel, Viviane Relvas, Fernanda Silva, Juliana Antunes, Graças Ribeiro, Roberta Bocalon, Rosária Otero, Rossana Terreri, Sandra Araujo, Meire Ishibashi; the CRT–DST/AIDS Nursing team, Aurelio Cruz, Pilar Hernandez, Griselda Diaz Garcia, Oscar Rojas Juarez, Rossane del Carmen Gonzales Sosa, Rene de Jesus Alvear Vazquez, Beibei Lu, Christine Gage, Kathy Eyring, Nadia Lambermont, Emily Jolles, Kayoko Kay, Kim Isaacs, Andrea Leto, Kyle Wolf, Anthony Bilotto, Abidemi Ajidahun, Michael Blackmer, Michael O’Keefe, Bradley Sirak, and Ray Viscidi, HIM Study Co-investigator, Johns Hopkins. Thanks also to Joel Palefsky, University of California, San Francisco, for ideas central to this article and to Digene Corp for donations of supplies.
Financial support.
This work was supported by the National Cancer Institute (NCI), National Institutes of Health (NIH) (1R03CA134204-01 and 3R03CA134204-02S1), the Investigator-Initiated Studies Program of Merck & Co (IISP33707 to A. G. N.), and NIH RO1 CA098803 01– A1 (to A. R. G.). Publication and report contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCI/NIH or Merck & Co.
Potential conflicts of interest.
A. G. N. received research funding from Merck & Co for the completion of this study. A. R. G. and L. L. V. are on the speakers’ bureau for Merck and are members of its advisory board. All other authors report no potential conflicts.
All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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