Human papillomavirus (HPV) is the world’s most common viral sexually transmitted infection [1, 2]. Approximately 40 HPV types infect anogenital squamous epithelium and can be broadly divided into low-risk (eg, HPV 6, 11) and high-risk (eg, HPV 16, 18) phenotypes based on their historical association with cervical cancer. This relationship also holds true for other anogenital (anal, vulvar, vaginal) and oropharyngeal malignancies. Although most HPV infections are asymptomatic, when symptoms do occur, they often reflect the presence of warts, dysplasia, or frank malignancy. Anogenital HPV infection is mostly transient in both sexes, with persistent high-risk HPV infection associated with the development of squamous-cell cancers [3, 4]. HPV prevalence data vary by gender, with men being more likely to have higher-level detection over a wider age range than women, whose prevalence decreases from a peak in their early 20s [3, 5] However, it is men who have sex with men (MSM) who have the highest rates of anogenital HPV infection and also HPV-associated malignancy, particularly HPV 16–associated anal cancer [6, 7]. HPV vaccination has been shown to be safe and effective in preventing the acquisition of anogenital HPV infection and the development of dysplasia [8–10]. The challenge ahead is to ensure that vaccinations are available to those at risk in a manner that optimizes their efficacy. There are 2 licensed HPV vaccines: a bivalent vaccine directed against HPV 16 and 18 (Cervarix, GlaxoSmithKline, London, UK) licensed for females aged 9–25 years, and a quadrivalent HPV vaccine (qHPV) directed against HPV 6, 11, 16, and 18 (Gardasil, Merck, Whitehouse Station, NJ) licensed for females and males ages 9–26 years. Both vaccines’ indications include prevention of warts and female genital dysplasia/cancer, with qHPV also indicated for anal dysplasia/ cancer. These prophylactic vaccines induce high-titer HPV antibody levels with good efficacy and an excellent safety profile [11, 12]. In this issue of The Journal of Infectious Diseases, Zou and colleagues examined acquisition of anogenital HPV in a population of MSM. They enrolled men between the ages of 16 and 20 years who self-identified as same-sex attracted. Thus, they were able to assess incident HPV infection in MSM with limited sexual experience who might benefit from HPV vaccination if they had the same access to HPV vaccines as adolescent girls. Following recruitment from a variety of venues, participants were seen for assessments at baseline and then at 3, 6, and 12 months. At each visit, participants had a clinical exam, completed a sexual experience questionnaire, had a blood sample drawn for HPV serology, and swabs taken from penile, perianal, and intra-anal sites. An oral saline gargle was also collected. All these samples were tested for HPV DNA by polymerase chain reaction. Additionally, participants were tested for gonorrhea, chlamydia, syphilis, and HIV at each visit. At the 12-month visit, participants were offered the qHPV. The median age of study participants was 19 years and the majority had engaged in both receptive and insertive anal intercourse. Thirty-nine percent of participants had at least 1 of 37 HPV types tested for at the anatomical sites sampled, and 23% had at least 1 qHPV type. Overall, at least 1 high-risk HPV was detected in 31% of participants. In participants with 0 to ≥4 receptive and insertive anal-sex partners, the respective proportion of anal (P < .001) and penile (P < .014) HPV increased significantly. This trend also reached significance for detection of anal HPV 16. In another study conducted in a slightly older age group of 94 MSM with a mean age of 21 years, 70% had any of the 37 HPV types tested for, and 37% had HPV 16 or 18. The incidence of anal HPV infection in this group was 38.5 and 15.3 per 1000 Received and accepted 4 November 2013. Correspondence: Ross D. Cranston, MB ChB, MD, FRCP, University of Pittsburgh, 3520 Fifth Ave, Keystone Bldg, Ste 510, Pittsburgh, PA 15213 (rdc27@pitt.edu). The Journal of Infectious Diseases © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/infdis/jit627