Prevalence of and Risk Factors for Human Papillomavirus (HPV) Infection Among HIV-Seronegative Men Who Have Sex With Men

MAJOR ARTICLE Prevalence of and Risk Factors for Human Papillomavirus (HPV) Infection Among HIV-Seronegative Men Who Have Sex With Men 1Mount Sinai School of Medicine, New York, New York; 2Department of Medicine, University of California, San Francisco, San Francisco, California; Assessment, Detection, and Intervention Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida; 4Associac xão Obras Sociais Irmã Dulce and Oswaldo Cruz Foundation, Brazilian Ministry of Health, Bahia, Brazil; 5University Medical Center, National Public Health Institute, Morelos, Mexico; 6J2: Private Clinic for Infectious Diseases, Berlin, Germany; 7STI Research Centre, University of Sydney, Sydney, Australia; 8Gynecologic Cancer Prevention Center, Medical College of Georgia, Augusta, Georgia; 9Centre de recherche du CHUM, Université de Montréal, Montreal, Quebec, Canada; 10Merck, North Wales, Pennsylvania; and 11Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston, Massachusetts 3Risk Background. We examined the baseline prevalence of penile, scrotal, perineal/perianal, and intra-anal human papillomavirus (HPV) infection in human immunodeficiency virus (HIV)–seronegative men who have sex with men (MSM). Methods. Data were analyzed from 602 MSM aged 16–27 years with <5 lifetime sexual partners. Serum samples were tested for antibodies to HPV6/11/16/18. Swab samples were collected separately from several anogenital areas for detection of HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59 DNA. Results. The prevalence of any tested HPV type was 18.5% at the penis, 17.1% at the scrotum, 33.0% at the perineal/ perianal region, 42.4% in the anal canal, and 48.0% at any site. Overall, 415 MSM (69.7%) were negative to HPV 6, 11, 16, and 18 at enrollment by both serology and DNA detection. Men residing in Europe and Latin America had significantly increased risk of HPV infection at external genital sites and the anal canal compared to men from Australia. Tobacco use and greater number of lifetime sexual partners was associated with higher HPV infection prevalence. Conclusions. The prevalence of HPV infection is high among young sexually active MSM, with the anal canal being the most common site of infection. Lifetime number of sexual partners was the most important modifiable risk factor for anogenital HPV infection. Human papillomavirus (HPV) is the most common sexually transmitted virus and causes a substantial Received 19 May 2010; accepted 30 July 2010. Potential conflicts of interest: EDM, DGF, ARG, and JMP have received research grants from Merck, either personally or through their institution. DGF has received research grants from GlaxoSmithKline. ARG, SG, DGF, RJH, and EDM have received honoraria from Merck for speaking engagements or board membership. SG, ARG, DGF, JMP, and EDM have received travel reimbursement from Merck related to scientific meetings. CA has an approved, filed, or pending patent related to subject matter discussed in this manuscript. EIOG, EB, RMH, DG, JBM, KLL, and SV are employees of Merck and may own Merck stock and/or stock options. Reprints or correspondence: Dr Stephen Goldstone, Mount Sinai School of Medicine, 420 West 23rd Street, New York, NY 10011 (). The Journal of Infectious Diseases 2011;203:66–74 Ó The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: 1537-6613/2011/2031-0001$15.00 DOI: 10.1093/infdis/jiq016 66 d JID 2011:203 (1 January) d Goldstone et al. burden of disease in men and women. Several studies have estimated the prevalence of HPV infection among men; however, these estimates vary widely, and the interpretation of these data are complicated by nonstandardized HPV sampling methods and differing patient populations[1]. Although many HPV infections in men have been shown to be transient in nature (similar to HPV infections in women), a small percentage persist and can progress to genital warts; preneoplastic and malignant lesions of the anus, penis, and oropharynx; and recurrent respiratory papillomatosis[2]. Previous studies have demonstrated a high prevalence of HPV infection among men who have sex with men (MSM)[3–5]. This high anal HPV prevalence among MSM is associated with an elevated anal cancer Stephen Goldstone,1 Joel M. Palefsky,2 Anna R. Giuliano,3 Edson D. Moreira Jr,4 Carlos Aranda,5 Heiko Jessen,6 Richard J. Hillman,7 Daron G. Ferris,8 Francois Coutlee,9 Kai-Li Liaw,10 J. Brooke Marshall,10 Xuehong Zhang,11 Scott Vuocolo,10 Eliav Barr,10 Richard M. Haupt,10 Dalya Guris,10 and Elizabeth I.O. Garner10 METHODS Subjects Protocol 020 was designed to evaluate the efficacy of quadrivalent HPV (types 6/11/16/18) L1 virus-like particle vaccine in young men (Gardasil, Merck). In addition to 3463 heterosexual men aged 16–24 years, the study enrolled 602 MSM aged 16–27 years with <5 lifetime male and/or female sexual partners. MSM were enrolled from 17 sites in Australia, Brazil, Canada, Croatia, Germany, Mexico, Spain, and the United States and were randomized and vaccinated from 30 November 2004 through 30 May 2007. Participants with ,1 lifetime male sexual partner must have identified themselves as an MSM and must have engaged in oral sex with another man within the past year. A male sexual partner was defined as a man with whom the participant engaged in receptive or insertive anal intercourse. Men with a history of or with current clinically detectable HPV-related genital lesions or other sexually transmitted diseases were excluded. Participants with known immunodeficiency or HIV infection were also excluded. Participants with HIV infection detected after enrollment were not excluded from the study. HPV or cytologic prescreening was not performed to determine eligibility for enrollment into the study[9]. All enrolled subjects underwent external genital lesion inspection and sampling for HPV DNA detection at baseline. If a lesion observed at baseline was judged by the investigator to be possibly HPVrelated or of unknown etiology, then the subject was excluded from the study. were collected separately from the penile, scrotal, perineal/perianal, and anal areas. A metal nail file was used to gently rub the penile skin. A Dacron swab moistened with sterile saline was used to collect cellular debris generated and then placed into a container of Digene (Qiagen) sample transport medium (STM). The procedure was repeated for the scrotum and perineal/perianal regions; each swab was placed in a separate STM vial. A fourth sample from the anal canal was obtained after a sample for cytology by inserting a moistened, nonlubricated Dacron swab a distance of 2–3 cm into the canal. The swab was rotated while moving it in and out several times to retrieve cells. All specimens were tested for the b-globin gene (positive control), and positive samples were tested for a panel of 14 HPV ty (...truncated)