Monitoring HPV vaccine impact: early results and ongoing challenges.

In this issue of the Journal of Infectious Diseases, Tabrizi and colleagues present new data from Australia on genital human papillomavirus (HPV) infection prevalence in the periods immediately before and after HPV vaccine introduction [1]. Based on cross-sectional studies of women aged 18–24 years who received Papanicolaou screening in selected family planning clinics throughout the country, the authors report a 20% decrease in overall genital HPV prevalence and a more dramatic decrease of 77% in HPV types targeted by the quadrivalent vaccine (HPV types 6, 11, 16, and 18) from the 2 years before (2005– 2007) to the 2 years after (2009–2010) the vaccine was widely implemented through a government-funded program. In addition to comparing HPV prevalence trends across periods, Tabrizi et al obtained HPV vaccination history from participants to more directly evaluate the effect of vaccination on HPV prevalence. Their results indicate significantly lower vaccine-type HPV prevalence among vaccinated women in the postvaccine sample (5.0%) compared with both unvaccinated women from the same period (15.8%) and women from the prevaccine period (28.7%). Using the age-adjusted HPV prevalence ratio of vaccinated to unvaccinated women, the authors calculate a vaccine effectiveness of 73% against infection with any of the 4 vaccine types. Because the major benefit of HPV vaccination—prevention of cervical and other less common HPV-associated cancers—will not be evident for decades, a spectrum of intermediate outcomes are being monitored to assess the early impact of HPV vaccines. Although considered to be the simplest and earliest indicator of vaccine impact, a reduction in HPV vaccine type prevalence may not be sufficient to guide vaccine policy and practices. Therefore, in addition to ongoing HPV type prevalence monitoring, cancer and precancer outcomes as well as HPV-associated genital warts are also included in the monitoring portfolios of most high-income and some middleand low-income countries where quadrivalent vaccine is being used [2, 3]. Although this study is the first to report a reduction in HPV vaccine type prevalence in Australia, it is not the first to suggest population impact of quadrivalent HPV vaccine. In fact, Australia was the first country to show reductions in genital warts associated with HPV types 6 and 11, which are targeted by the quadrivalent vaccine [4, 5]. Genital warts develop soon after HPV infection and can be an early indicator of vaccine impact in countries where the quadrivalent vaccine is exclusively or predominantly used. Published in 2009, the study from Melbourne, Australia, demonstrated progressive and significant decreases in new genital warts diagnoses <3 years after vaccine introduction among young women in the age group targeted for vaccination [4]. The Australia data also showed significant decreases in young heterosexual men during the same period, suggesting possible herd immunity in the population. Since the publication of that study, a new analysis examining data through June 2011 suggests that genital warts have nearly disappeared in the same population of females and males <21 years of age [6]. More recently, ecologic data emerging from the United States suggest a decrease in rates of genital warts diagnoses in young women despite the lower vaccine coverage [7]. Another intermediate outcome, which can be used to monitor bivalent or quadrivalent vaccine, is high-grade cervical lesions that can develop into invasive cancer if not treated. These precancerous lesions were used as the primary endpoints in the vaccine clinical trials. Although cervical lesions can take years after infection to become clinically detectable, in 2010, a study co-authored by some authors on the present study reported a significant decrease in highgrade lesions among girls aged <18 years who were screened for cervical cancer in Victoria, Australia [8]. Because Received and accepted 19 July 2012; electronically published 19 October 2012. Correspondence: Susan Hariri, PhD, Center for Disease Control and Prevention, 1600 Clifton Rd, MS E-02, Atlanta, GA 30333 ([email protected]). The Journal of Infectious Diseases 2012;206:1633–5 Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2012. DOI: 10.1093/infdis/jis593