Factors affecting the prevalence of strongly and weakly carcinogenic and lower-risk human papillomaviruses in anal specimens in a cohort of men who have sex with men (MSM)

Background: MSM are at higher risk for invasive anal cancer. Twelve human papillomaviruses (HPVs) cause cervical cancer in women (Group 1 high-risk HPVs (hrHPVs)) and 13 HPVs are probable/possible causes (Group 2 hrHPVs) of cervical malignancy. HPVs rarely associated with malignancy are classified as lower-risk HPVs (lrHPVs). Materials and Methods: Dacron-swab anal-cytology specimens were collected from and data complete for 97% (1262/1296) of Multicenter AIDS Cohort Study (MACS) men tested for HPVs using the Linear Array assay. Multivariate Poisson regression analyses estimated adjusted prevalence ratios for Group 1/2 hrHPVs and lrHPVs, controlling for the effects of age, race, ethnicity, sexual partnerships, smoking; HIV-infection characteristics, treatment, and immune status among HIV-infected men. Results: HIV-infected men showed 35-90% higher prevalence of Group 1/2 hrHPVs and lrHPVs than HIV-uninfected men, and higher prevalence of multi-Type, and multiple risk-group infections. CD4+ T-cell count was inversely associated with HPV Group 2 prevalence (p<0.0001). The number of receptive anal intercourse (RAI) partners reported in the 24 months preceding HPV testing predicted higher prevalence of Group 1/2 hrHPVs. Men reporting ≥30 lifetime male sex partners before their first MACS visit and men reporting ≥1 RAI partners during the 24 months before HPV testing showed 17-24% and 13-17% higher prevalence of lrHPVs (p-values ≤0.05). Men reporting smoking between MACS visit 1 and 24 months before HPV testing showed 1.2-fold higher prevalence of Group 2 hrHPVs (p = 0.03). Both complete adherence to CART (p = 0.02) and HIV load <50 copies/mL (p = 0.04) were protective for Group 1 hrHPVs among HIV-infected men. Conclusions: HIV-infected men more often show multi-type and multi-group HPV infections HIV-uninfected men. Long-term mutual monogamy and smoking cessation, generally, and CART-adherence that promotes (HIV) viremia control and prevents immunosuppression, specifically among HIV-infected MSM, are important prevention strategies for HPV infections that are relevant to anal cancer. © 2013 Wiley et al

Association between free testosterone levels and anal human papillomavirus types 16/18 infections in a cohort of men who have sex with men.

BackgroundHuman papillomavirus (HPV) types 16 and 18 cause invasive cervical cancer and most invasive anal cancers (IACs). Overall, IAC rates are highest among men who have sex with men (MSM), especially MSM with HIV infection. Testosterone is prescribed for men showing hypogonadism and HIV-related wasting. While there are direct and indirect physiological effects of testosterone in males, its role in anal HPV16/18 infections in men is unknown.MethodsFree testosterone (FT) was measured in serum from 340 Multicenter AIDS Cohort Study (MACS) participants who were tested for anal HPV16/18-DNA approximately 36 months later. The effect of log10-transformed current FT level on anal HPV16/18 prevalence was modeled using Poisson regression with robust error variance. Multivariate models controlled for other HPV types, cumulative years of exogenous testosterone use, race, age, lifetime number of receptive anal intercourse partnerships, body mass index, tobacco smoking, HIV-infection and CD4+ T-cell counts among HIV-infected, and blood draw timing.ResultsParticipants were, on average, 60 (+5.4) years of age, White (86%), and HIV-uninfected (56%); Twenty-four percent tested positive for anal HPV16 and/or 18-DNA (HPV16 prevalence=17.1%, HPV18=9.1%). In adjusted analysis, each half-log10 increase of FT was associated with a 1.9-fold (95% Confidence Interval: 1.11, 3.24) higher HPV16/18 prevalence. Additionally, other Group 1 high-risk HPVs were associated with a 1.56-fold (1.03, 2.37) higher HPV16/18 prevalence. Traditional risk factors for HPV16/18 infection (age, tobacco smoking; lifetime number of sexual partners, including the number of receptive anal intercourse partnerships within 24 months preceding HPV testing) were poorly correlated with one another and not statistically significantly associated with higher prevalence of HPV16/18 infection in unadjusted and adjusted analyses.ConclusionsHigher free testosterone was associated with increased HPV16/18 prevalence measured approximately three years later, independent of sexual behavior and other potential confounders. The mechanisms underlying this association remain unclear and warrant further study

A–D: Age-specific Prevalence of Group 1 and 2 High-risk HPVs and Lower-risk HPVs for 1262 Men Enrolled in the Multicenter AIDS Cohort Study Anal Health Sub-study.

<p>(A) Virus Type Group-specific Prevalence for All Men. (B–D) Comparison of 579 HIV-infected and 683–Uninfected Men for (B) Group 1 High-risk HPVs, (C) Group 2 High-risk HPVs, and (D) Lower-risk HPVs.</p

Sociodemographic Characteristics, Sexual Behavior Characteristics, HIV, and Human papillomavirus (HPV) infection Characteristics of 1262 Multicenter AIDS Cohort Study Participants Evaluated for HPV DNA using Anal Swab Specimens.

a<p><i>p</i><0.001, ^b<i>p</i> = 0.037, ^c<i>p</i><0.001, ^dcategories are not mutually exclusive, ^e<i>p</i> = 0.062; ^f<i>p</i> = 0.138^g<i>p</i><0.001. P-values for comparing HIV+ vs. HIV- were by the Fisher exact test or the Wilcoxon nonparametric test, as appropriate.</p

Comparison of Prevalence Ratios for Group 1 and 2 High-risk and Lower-risk HPVs for 579 HIV-infected Men Enrolled in the Multicenter AIDS Cohort Study Anal Health Sub-study.^a

<p>Comparison of Prevalence Ratios for Group 1 and 2 High-risk and Lower-risk HPVs for 579 HIV-infected Men Enrolled in the Multicenter AIDS Cohort Study Anal Health Sub-study.^a</p

HPV-Infection Characteristics Among 1005 MACS MSM Showing One or More HPVs for Single and Multiply Detected HPV-Types.

a<p><i>p</i><0.05 Comparing prevalence of infection for HIV+ to HIV-negative men.</p

Characteristics of 340 Men Who Have Sex with Men Who Were Tested for Anal HPV DNA and Free Testosterone by HPV16/18 Positivity.

<p>^a Positive for either HPV16 or HPV18 or both</p><p>^b Fisher’s Exact (2-sided) p-values: comparisons between groups in total population; NS: <i>p</i>≥0.05</p><p>^c HCV antibody positivity</p><p>Characteristics of 340 Men Who Have Sex with Men Who Were Tested for Anal HPV DNA and Free Testosterone by HPV16/18 Positivity.</p

Univariate and Four Iterations of Multivariate Evaluation of Risk Factors for Anal HPV16/18 DNA Positivity for 340 Men Who Have Sex with Men.^a

<p>^a Statistically significant associations appear in bold type-face, <i>p</i><0.05</p><p>^b Additionally controlled for Hepatitis C virus (HCV), smoking and alcohol use prior to baseline and testosterone testing visit, cumulative pack years prior to baseline, testosterone visit, and HPV testing visit, study site, and time cohort, QIC = 508.5534.</p><p>^c Additionally controlled for Hepatitis C virus (HCV), alcohol use prior to HPV testing visit, study site, and time cohort, QIC = 501.2063.</p><p>^d Additionally controlled for study site, and time cohort, QIC = 506.7745.</p><p>^e QIC = 491.2723</p><p>Univariate and Four Iterations of Multivariate Evaluation of Risk Factors for Anal HPV16/18 DNA Positivity for 340 Men Who Have Sex with Men.<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119447#t003fn001" target="_blank">^a</a></p