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)

et al. (2013) 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). PLoS ONE 8(11): e79492. doi:10.1371/journal.pone.0079492 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) Dorothy J. Wiley 0 Xiuhong Li 0 Hilary Hsu 0 Eric C. Seaberg 0 Ross D. Cranston 0 Stephen Young 0 Gypsyamber D'Souza 0 Otoniel Martnez-Maza 0 Katherine DeAzambuja 0 Kristofer Chua 0 Shehnaz K. Hussain 0 Roger Detels 0 Clive M. Gray, University of Cape Town, South Africa 0 1 School of Nursing, University of California Los Angeles , Los Angeles , California, United States of America, 2 Bloomberg School of Public Health, Johns Hopkins University , Baltimore , Maryland, United States of America, 3 School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America , 4 Tricore Diagnostic Laboratories , University of New Mexico , Albuquerque , New Mexico, United States of America, 5 David Geffen School of Medicine at University of California Los Angeles , Los Angeles , California, United States of America, 6 UCLA AIDS Institute, University of California Los Angeles , Los Angeles , California, United States of America, 7 Jonathan and Karen Fielding School of Public Health, University of California Los Angeles , Los Angeles, California , United States of America 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 HIVinfected 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. Longterm 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. - Funding: The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID, http://www.niaid.nih.gov/Pages/default.aspx), with additional co-funding from the National Cancer Institute (NCI, www.cancer.gov). Grant numbers: Baltimore (U01-AI-35042), Chicago (U01-AI-35039), Los Angeles (U01-AI-35040), Pittsburgh (U01-AI-35041), and Data Coordinating Center (UM1-AI-35043). Targeted supplemental funding for specific projects was also provided by the National Heart, Lung, and Blood Institute (NHLBI, http://www.nhlbi.nih.gov), and the National Institute on Deafness and Communication Disorders (NIDCD, http://www.nidcd.nih.gov/Pages/default.aspx). MACS data collection is also supported by the Johns Hopkins University Clinical and Translational Science Awards: UL1TR000424(JHU CTSA, (http://ictr.johnshopkins.edu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: Wiley, Cranston and DSouza receive research funding from Merck, Sharp, & Dohme (Merck & Co., Inc). Wiley has been paid for educational lectures to healthcare providers by Merck & Co., Inc. Cranston has received honoraria for published works for Wolters Kluwer, publishers of UptoDate.com. Young is a member of a scientific advisory board for Roche Diagnostic Corporation & Quidel Corporation. This does not alter the authors adherence to all the PLOS ONE policies on sharing data and materials. None of these entities funded this work. Other authors have declared that no competing interests exist. Invasive anal cancer (IAC) is a health crisis for gay, bisexual, and other men who have sex with men (MSM). Overall, IAC rates have increased steadily among U.S. men between 19752008, but risk among HIV-infected MSM has increased greatly since the introduction of combined antiretroviral therapy (CART) for HIV infection in the late 1990 s [15]. Current domestic IAC incidence estimates among MSM surpass contemporary invasive cervical cancer rates in women as well as rates reported when domestic mass cervical cytology screening was initiated in the 1950 s [2,4,6 11]. Currently, domestic IAC incidence rates among HIV-infected MSM surpass rates for 7 of the top 10 cancers, 1336 cases/ 100,000, and even exceeds the third most common cancer, colorectal cancer, for all U.S. males: conservatively, 78 vs. 53/ 100,000, respectively [1,2,4,12,13]. Human papillomaviruses (HPVs) infect epithelial cells and show varying degrees of pathogenicity from warts to invasive cancers. Until recently, 14 viruses were referred to as high-risk HPVs (hrHPVs): HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, and 69 [14,15]. Currently, the first 12 are classified as Group 1 hrHPVs, and considered necessary but insufficient causes of cervical cancer by the International Agency for Research on Cancer (IARC) [14]. Among these, HPV16 is considered most pathogenic and is detected most often in cancers [14]. Experts generally agree that most Group 1 hrHPVs are strong carcinogens [16]. Additionally, IARC recently regrouped HPV68 and 69, together with 11 other viruses, HPV26, 30, 34, 53, 66, 67, 70, 73, 82, 85, and 97 as probable or possible, weaker carcinogens, collectively evaluated as Group 2 hrHPVs [14,16]. Low-grade dysplasias, such as genital warts, are commonl (...truncated)