Human Papillomavirus: The Equal Opportunity Pathogen

The Journal of Infectious Diseases E D I T O R I A L C O M M E N TA R Y Human Papillomavirus: The Equal Opportunity Pathogen Patti E. Gravitt Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington, D. C. (See the major article by Gargano et al on pages 1070–9.) Keywords. age; female; human papillomavirus; male; prevalence. Received 23 January 2017; editorial decision 23 January 2017; accepted 28 January 2017; published online February 7, 2017. Correspondence: P. E. Gravitt, PhD, MS, Department of Global Health, Milken Institute School of Public Health, George Washington University, 800 22nd St NW, Science and Engineering Hall, Rm 7850, Washington, DC 20052 (pgravitt@ gwu.edu). The Journal of Infectious Diseases®  2017;215:1014–6 © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: . DOI: 10.1093/infdis/jix058 men aged 14–59 years [4] and in 42.5% of women of the same age group [2]. Similarly, just under 1 in 4 US men (23.4%) and US women (23.7%) had detectable genital HR-HPV at the time of surveillance [2]. It is important to note that these data reflect the burden of currently detectable genital HPV infection and contrast with the previously reported 2-fold difference in prevaccination-era seroprevalence against ≥1 of 9 HPV types included in the most recent HPV vaccine formulation (Gardasil9; 9vHPV), showing an approximately 2-fold higher 9vHPV seroprevalence in women (40.5%), compared with men (19.4%) [5]. Taken together, it appears that any gender disparity related to genital HPV infection is due to a lower probability of seroconversion after infection in men, compared with women (at least to detectable levels), rather than to any real differences in infection prevalence [6]. Gargano et al [4] note that, despite the gender similarities in overall HPV prevalence, the age-specific HPV prevalence pattern reported in US male and female participants was different, particularly in the youngest (14–24 years) and oldest (40–59 years) age groups (Figure 1). Mechanisms posited by the authors include a plausible combination of men having more new sex partners throughout their lifespan and a lower probability of seroconversion (and thus lower protective immune response from new infection or reinfection), compared with women. Recent sexual activity, as measured in the NHANES by the number of sex partners in the past 12 months, was only associated with a modestly 1014 • JID 2017:215 (1 April) • EDITORIAL COMMENTARY increased prevalence of HPV in men (adjusted prevalence ratio [aPR], 1.26), suggesting that acquisition of a new sex partner may not contribute substantially to the overall prevalence at older ages. In fact, report of multiple sex partners declined with increasing age. Since this assessment cannot preclude new exposures from men who acquired a single new sex partner in the past 12 months and may include men with multiple stable partnerships, it does not represent an ideal exposure to capture potentially new infection opportunities. However, other surveys of adult sexual behavior confirm decreased opportunities for new sexual exposures in men with increasing age. For example, the National Survey of Sexual Health and Behavior reported a peak in the percentage reporting having any vaginal sexual intercourse in the past year in men aged 30–39 years (85.3%), declining in each subsequent age decile (73.6%, 57.9%, 53.5%, and 42.9% at ages 40–49, 50–59, 60–69, and ≥70 years, respectively) [7]. The British National Surveys of Sexual Attitudes and Lifetsyles (Natsal) asked specifically about having a new sex partner in the past year and found a similar decline in the percentage of men responding affirmatively (46.0%, 26.3%, 13.2%, 12.3%, 10.4%, and 5.0% at ages 16–24, 25–34, 35–44, 45–54, 55–64, and 65–74 years, respectively) [8]. While the Natsal data may not be directly generalizable to the US population, the percentage of men reporting multiple sex partners in that study was similar to that in the NHANES, suggesting similar patterns of behavior in the US and United In 2003, following initial reports of high efficacy for prevention of human papillomavirus (HPV) through prophylactic vaccine, the Centers for Disease Control and Prevention incorporated surveillance for genital HPV infection in women as part of the biannual National Health and Nutrition Examination Surveys (NHANES) [1]. With >10 years of follow-up, these efforts have illuminated the high burden and the age-specific distribution of female genital HPV and, most recently, the population impact of HPV vaccination in reducing quadrivalent HPV vaccine (4vHPV)–associated genotypes among US women [1–3]. In this issue of The Journal of Infectious Diseases, Gargano et al report the genital HPV prevalence in the other half of the population—a nationally representative sample of US men, included in the NHANES for the first time in 2013–2014 [4]. These data, compared with previously published estimates in women [2], confirm that the burden of genital HPV is shared equally by men and women in the United States. Specifically, penile HPV infection with any one or more of 37 HPV genotypes (ie, high-risk HPV [HR-HPV] and/ or low-risk HPV) was detected in 42.2% of Figure 1. Age-specific prevalence of human papillomavirus (HPV; any type) among US female (2003–2006) [2] and male (2013–2014) [4] study participants. but not female estimates include cohort effects of both female and male vaccination during 2006–2014. Such effects are evident when considering the differences in age-specific patterns of 4vHPV and non-4vHPV genotypes reported by Gargano et al, which show a similar lack of parallel changes between ages 14 and 24 years as the female-to-male comparisons in Figure 1. Since age at sexual debut across birth cohorts reported in the NHANES was not substantially different in men and women [12], it is likely that at least some of the lower prevalence in men at younger ages in the published NHANES studies is related to the fact that these men were sampled in the postvaccine era, whereas the female data reflect a prevaccine-era sampling. An earlier cohort effect may contribute to the sex difference in HPV prevalence at older ages. Lifetime number of sex partners, strong determinants of HPV prevalence in both sexes, have changed significantly over time in the United States, particularly in women [13]. The most dramatic age-specific genital HPV prevalence difference in the data represented in Figure 1 is in the 50–59-year age group, which spans the 1944–1956 birth cohorts in women (median lifetime number of sex partners, 2.6–3.8) and the 1955–1963 birth cohorts in men (median lifetime number of sex partners, 7.9–8.9) [12]. If reactivation of latent infection is a significant source of HPV infection at older ages, as has been suggested by multiple studies in women [14–17], (...truncated)