What Drives the Number of High-Risk Human Papillomavirus Types in the Anal Canal in HIV-Positive Men Who Have Sex With Men?

Julia Del Amo ) 2 3 Cristina Gonzlez 2 3 Ronald B. Geskus 2 9 Montse Torres 1 2 Jorge Del Romero 0 2 Pompeyo Viciana 2 6 Mar Masi 2 5 Jose R. Blanco 2 4 Beatriz Hernndez-Novoa 2 8 Marta Ortiz 1 2 on behalf of CoRIS-HPV Study Group 2 7 0 Sanitary Center Sandoval 1 National Center of Microbiology, Institute of Health Carlos III 2 Received 6 July 2012; accepted 20 November 2012; electronically published 16 January 2013 3 National Center of Epidemiology 4 San Pedro-CIBIR Hospital , Logrono , Spain 5 Elche Universitary Hospital , Alicante 6 Virgen del Rocio Hospital , Sevilla 7 Members of the study group are listed at the end of the text. Presented in part: XIXthe International AIDS Conference , Washington, D. C., 20 July 2012. Poster number: TUPE 135. ogy , Institute of Health Carlos III , Av. Monforte de Lemos no. 5, CP, 28029 Madrid , Spain ( 8 Ramon y Cajal Hospital , Madrid 9 Amsterdam Health Service and Academic Medical Center , Netherlands We estimated the effect of sexual behavior, age, and immunodeficiency on the number of high-risk human papillomavirus (HR-HPV) types in the anal canal among human immunodeficiency virus-positive men who have sex with men (MSM). Anal samples were genotyped with the Linear Array HPV Genotyping Test, and risk factors were investigated with Poisson regression. Of 586 MSM, 69% were Spanish, and 25.6% were Latin American; the median age was 34.9 years (interquartile range [IQR], 30.1-40.8). The median number of recent sex partners was 6 (IQR, 2-24 sex partners), and the median CD4+ T-cell count was 531.5 cells/mm3 (IQR, 403-701 cells/mm3). The prevalence of any and multiple HR-HPV infections was 83.4% and 60.5%, respectively. The most common types were HPV-16 (42%), HPV-51 (24%), HPV-39 (23.7%), and HPV-59 (23.5%). Age had a statistically significant, nonlinear association with the number of types, with the highest number detected around 35 years of age (P < .001). The number of recent sex partners had a statistically significant, fairly linear association on the log scale (P = .033). The high prevalence of HR-HPV types is associated with recent sexual behavior and age. - HR-HPV; HIV; MSMS; sexual behavior; anal cancer. Infection with high-risk human papillomavirus (HRHPV) among human immunodeficiency virus (HIV) positive men who have sex with men (MSM) is extremely common [15]. Around 90% of HIV-positive MSM are coinfected with HR-HPV [15], a prevalence that is considerably higher than that among HIV-negative MSM [2, 6, 7]. Furthermore, the prevalence of multiple HR-HPV types among HIV-positive MSM has also been reported to be very high, at nearly 60% [2, 7], which is important because infection with multiple HR-HPV types is associated with a higher prevalence of anal intraepithelial neoplasia in this population [811]. Infection with HR-HPV types is a necessary cause of anal carcinoma, an emerging tumor whose incidence is increasing among MSM, particularly those infected with HIV [1219]. Anal carcinoma is considered an opportunistic tumor, although it is not part of the AIDS case definition, in contrast with cervical carcinoma, which became an AIDS-defining condition in 1993 [20]. The very high prevalence of infection with multiple HR-HPV types among HIV-positive MSM could be driven by an increased persistence of HR-HPV infections due to compromised immunity and/or to a high incidence of new infections driven by sexual behavior, but to date, this has not been established. To address this question, we investigated the effect of self-reported past and current sexual behavior, age, and immunodeficiency on the number of baseline HR-HPV types in the anal canal in HIV-positive MSM. CoRIS-HPV is a cohort study within CoRIS, the cohort of the Spanish Network of Excellence on HIV/AIDS Research. CoRIS is an open and multicenter cohort established in January 2004 that consists of adult patients with confirmed HIV infection who were naive to combined antiretroviral therapy (cART) at study entry. Patients are followed periodically according to routine clinical practice, usually every 4 months. Ethical approval and signed informed consent were obtained from each CoIRIS participant [21]. CoRIS-HPV was set up in January 2007 to study the epidemiology of HR-HPV coinfection in 12 of the 28 sites that contribute data to CoRIS. Study subjects are informed about the nature of the study and are required to provide written informed consent specific to CoRIS-HPV, in addition to the consent for the main CoRIS study. Specific ethical approval for this study has been obtained, as well (ISCIII Ethical Comite reference number PI-43). Besides the variables collected in CoRIS, subjects are requested to answer a questionnaire on sexual behavior (age at first sexual intercourse; lifetime number of sex partners; number of sex partners in the past 12 months; and frequency of unsafe sex, measured by the frequency of condom use during anal intercourse in the past 12 months), history of genital warts, and smoking history. Anal samples are processed for HR-HPV DNA detection and cytological analyses. We restrict this article to the analysis of baseline data, which were obtained at cohort entry. The outcome variable for current analyses was the number of HR-HPV types at baseline. Separate analyses for single HPV-16 and HPV-18 infections were also performed. The variables capturing self-reported past sexual behavior were age at first sexual intercourse and lifetime number of sex partners, and variables for current sexual behavior were number of sex partners in the past 12 months and having had unsafe sex. The variable capturing immunodeficiency was CD4+ T-cell count at baseline (ie,within 6 months of collection of the HR-HPV anal sample). The following variables were conceptualized as potential confounders for the relation between age, sexual behavior, and immune status and the outcome: geographic origin (categorized as Europe, Latin-America, and other), education level (categorized as none/primary, secondary, and university), and smoking history (categorized as current smoker, past smoker, and never smoker). HPV DNA Detection and Genotyping Samples were collected with a citobrush and placed in 1 mL of specimen transport medium (Qiagen, Gaithersburg, MD), sent to the Retroviruses and Papillomavirus Unit of the National Center for Microbiology in Madrid, and stored at 20C until required for testing. Anal HR-HPV infection was genotyped using polymerase chain reaction (PCR) amplification, followed by reverse line blot hybridization, using the Linear Array HPV Genotyping test (Roche Molecular Systems, Branchburg, NJ). DNA was extracted from a 200-L aliquot of the original anal samples, using an automatic DNA extractor (Biorobot M48 Robotic Workstation, Qiagen). For quality control, each extraction run included 10 samples, 1 negative control (water of PCR quality) and 4 positive controls (SiHa cells infected with HPV 16). The results were considered satisfactory if there we (...truncated)