Anal, Penile, and Oral High-Risk HPV Infections and HPV Seropositivity in HIV-Positive and HIV-Negative Men Who Have Sex with Men

and Oral High-Risk HPV Infections and HPV Seropositivity in HIV-Positive and HIV-Negative Men Who Have Sex with Men. PLoS ONE 9(3): e92208. doi:10.1371/journal.pone.0092208 Anal, Penile, and Oral High-Risk HPV Infections and HPV Seropositivity in HIV-Positive and HIV-Negative Men Who Have Sex with Men Vera M. van Rijn 0 Sofie H. Mooij 0 Madelief Mollers 0 Peter J. F. Snijders 0 Arjen G. C. L. Speksnijder 0 Audrey J. King 0 Henry J. C. de Vries 0 Arne van Eeden 0 Fiona R. M. van der Klis 0 Hester E. de Melker 0 Marianne A. B. van der Sande 0 Maarten F. Schim van der Loeff 0 Luwen Zhang, University of Nebraska - Lincoln, United States of America 0 1 Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands, 2 Cluster of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, the Netherlands, 3 Department of Pathology, VU University Medical Center , Amsterdam, the Netherlands, 4 Center for Infection and Immunity Amsterdam (CINIMA) , Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands, 5 Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands, 6 Department of Internal Medicine, Jan van Goyen Medical Center, Amsterdam, the Netherlands, 7 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht , Utrecht , the Netherlands The effects of single or multiple concordant HPV infections at various anatomical sites on type-specific HPV seropositivity are currently unknown. In this cross-sectional study we assessed whether high-risk HPV infections at various anatomical sites (i.e., anal canal, penile shaft, and oral cavity), as well as concordant infections at multiple anatomical sites, were associated with type-specific seropositivity in HIV-positive and HIV-negative MSM. MSM aged $18 years were recruited in Amsterdam, the Netherlands (2010-2011). Baseline anal, penile, and oral samples were analyzed for HPV DNA and genotyped using a highly sensitive PCR and reverse line blot assay. Virus-like particle (VLP) based multiplex immunoassay was used to asses HPV-specific serum antibodies against L1 VLPs. The associations between HPV infections and type-specific seropositivity of seven high-risk HPV types (7-hrHPV: types 16, 18, 31, 33, 45, 52, 58) were estimated using logistic regression analyses with generalized estimating equations. We found that 86% of 306 HIV-positive MSM and 62% of 441 HIV-negative MSM were seropositive for at least one 7-hrHPV type. 69% of HIV-positive and 41% of HIV-negative MSM were infected with at least one 7-hrHPV type at the anus, penis, or oral cavity. In multivariable analyses, 7-hrHPV seropositivity was associated with type-specific anal (and not penile) 7-hrHPV infection, and did not significantly increase with a higher number of infected anatomical sites. Oral 7-hrHPV infection showed a positive, albeit non-significant, association with seropositivity. In conclusion, seropositivity among MSM appears to be largely associated with anal HPV infection, irrespective of additionally infected anatomical sites. - Funding: This study was funded through a grant from the Aids Fonds (grant number 2009029) and additional funding from the Public Health Service of Amsterdam and the RIVM. The Amsterdam Cohort Studies on HIV infection and AIDS, a collaboration between the Public Health Service of Amsterdam, the Academic Medical Center of the University of Amsterdam, Sanquin Blood Supply Foundation, and the University Medical Center Utrecht, are part of the Netherlands HIV Monitoring Foundation and financially supported by the Netherlands National Institute for Public Health and the Environment. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: MSvdL received funding for a substudy on HPV from Sanofi Pasteur MSD and participates in a Merck-funded investigator-initiated study on Gardasil. This does not alter the authors adherence to PLOS ONE policies on sharing data and materials. For the remaining authors no conflicts of interest were declared. . These authors contributed equally to this work. Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections worldwide [1]. Persistent infection with high-risk HPV types is a leading cause of anogenital cancers and of a subset of oropharyngeal cancers [2]. A high prevalence of anal, penile, and oral HPV infections has been observed among men who have sex with men (MSM) [36] with an even higher prevalence among HIV-positive MSM [510]. In the majority of individuals an HPV infection is cleared within 420 months [11,12]. Individuals naturally infected with HPV do not always develop antibody responses over time [13,14]. If seroconversion does occur, antibodies may persist for many years [15]. Seropositivity is thought to be associated with persistent HPV infection, HPV viral load, and anatomical site of infection [13,16 22]. Previous studies observed that HPV seropositivity was positively associated with type-specific anal HPV infection rather than with genital (penile) HPV infection [2022]. Also, seropositivity was higher among HIV-positive than HIV-negative MSM [23]. However, studies on the association between high-risk HPV infections at various anatomical sites and type-specific HPV seropositivity in MSM with and without HIV infection are scarce. Moreover, to the best of our knowledge no study has investigated the associations of concordant infections at multiple anatomical sites with HPV seropositivity. Since HPV antibodies are generally regarded as a marker of lifetime HPV exposure, more insight into antibody responses will assist in the interpretation of seroepidemiological studies and in targeting HPV prevention strategies. In this cross-sectional study we assessed whether high-risk HPV infections at various anatomical sites (i.e., anal canal, penile shaft, and oral cavity), as well as concordant infections at multiple anatomical sites, are associated with type-specific seropositivity in HIV-positive and HIV-negative MSM. Materials and Methods Ethics statement The Medical Ethics Committee of the Academic Medical Center (AMC) in Amsterdam approved the study. Written informed consent was obtained from all participants prior to enrollment. Study population This analysis is based on baseline data of the HIV & HPV in MSM (H2M) study, a prospective cohort study which aims to compare the prevalence, incidence, and clearance of anal, penile, and oral HPV infections in HIV-positive and HIV-negative MSM. Details of the H2M study and study population have been described previously [5]. In brief, HIV-positive and HIV-negative MSM were recruited from three sites in Amsterdam, the Netherlands: the Amsterdam Cohort Study among MSM [24], an STI clinic (both at the Public Health Service of Amsterdam), and an outpatient (...truncated)