Association of Chlamydia trachomatis Infection and Herpes Simplex Virus Type 2 Serostatus With Genital Human Papillomavirus Infection in Men: The HPV in Men Study

Alberts, Catharina Johanna MSc*†; Schim van der Loeff, Maarten F. MD, PhD*†; Papenfuss, Mary R. MS; da Silva, Roberto José Carvalho PhD§; Villa, Luisa Lina PhD; Lazcano-Ponce, Eduardo PhD#; Nyitray, Alan G. PhD**; Giuliano, Anna R. PhD

Sexually Transmitted Diseases: June 2013 - Volume 40 - Issue 6 - p 508–515
doi: 10.1097/OLQ.0b013e318289c186
Original Study

Background: Studies in women indicate that some sexually transmitted infections promote human papillomavirus (HPV) persistence and carcinogenesis. Little is known about this association in men; therefore, we assessed whether Chlamydia trachomatis (CT) infection and herpes simplex virus type 2 (HSV-2) serostatus are associated with genital HPV prevalence, an early event in HPV-related pathogenesis.

Methods: Genital exfoliated cells, first-void urine, and blood from 3971 men recruited in the United States, Mexico, and Brazil were tested for HPV, CT, and HSV-2 antibodies, respectively. Multivariable logistic regression was used to assess the association of CT infection and HSV-2 serostatus with 4 HPV outcomes (any, oncogenic, nononcogenic only, and multiple infections).

Results: A total of 64 (1.6%) men were CT positive, and 811 (20.4%) men were HSV-2 seropositive. After adjustment for potential confounders, CT was associated with any HPV (adjusted odds ratio [aOR], 2.19; 95% confidence interval [CI], 1.13–4.24), oncogenic HPV (aOR, 3.10; 95% CI, 1.53–6.28), and multiple HPV (aOR, 3.43; 95% CI, 1.69–6.95) prevalence. Herpes simplex virus type 2 serostatus was associated with any HPV (aOR, 1.25; 95% CI, 1.02–1.52), nononcogenic HPV only (aOR, 1.38; 95% CI, 1.08–1.75), and multiple HPV (aOR, 1.33; 95% CI, 1.06–1.68) prevalence. In analyses stratified by sexual behavior, CT infection was significantly associated with HPV detection among men reporting 2 or more recent sexual partners, whereas HSV-2 serostatus was significantly associated with HPV detection in men reporting 0 to 5 lifetime sexual partners.

Conclusion: In this population, CT infection and HSV-2 serostatus were associated with prevalent genital HPV infection. Future prospective studies should investigate whether these infections influence HPV acquisition and/or persistence.

In a large cohort study in men, both Chlamydia trachomatis infection and herpes simplex virus type 2 serostatus were associated with prevalent genital human papillomavirus infection.

From the *Cluster of Infectious Diseases, GGD Amsterdam, the Netherlands; †Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, the Netherlands; ‡Center for Infection Research in Cancer, H. Lee Moffitt Cancer Center, Tampa, FL; §Centro de Referencia e Treinamento em DST/Aids, São Paulo, Brazil; ¶Department of Radiology and Basic Oncology, School of Medicine, University of São Paulo and Cancer Institute of the State of São Paulo, ICESP, São Paulo, Brazil; #Instituto Nacional de Salud Pública, Cuernavaca, Mexico; and **University of Texas–School of Public Health at Houston, Center for Infectious Diseases, Houston, TX

The authors thank all participants who provided personal information and biological samples for the study and the HPV in Men study teams in the United States (Tampa), Brazil (São Paulo), and Mexico (Cuernavaca). They also thank Susan T. Landry for editorial review. The HPV in Men study was supported through a grant from the National Cancer Institute, US National Institutes of Health (CA R01CA098803).

Conflict of interest: M.F. Schim van der Loeff receives research funding from Merck and Sanofi-Pasteur MSD. A.G. Nyitray receives research funding from Merck. A.R. Giuliano receives research funding from Merck and GSK and is also a consultant to Merck, is a member of the Merck HPV Advisory Board, and is on the speakers’ bureau. L.L. Villa is on the speakers’ bureau of Merck and is also a member of its advisory board. Other authors of this study declare no commercial or other association that might pose a conflict of interest for the work submitted.

This article is in partial fulfillment of C.J. Alberts’ PhD thesis.

Correspondence: Anna R. Giuliano, PhD, Center for Infection in Cancer Research, Moffitt Cancer Center, 12902 Magnolia Dr, MRC CANCONT, Tampa, FL 33612. E-mail:

Received for publication November 19, 2012, and accepted January 24, 2013.

© Copyright 2013 American Sexually Transmitted Diseases Association