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A prophylactic quadrivalent human papillomavirus (HPV) vaccine could benefit adult women if they are susceptible to incident genital HPV infections and are acquiring new infections with vaccine HPV types to which they were previously not exposed. This report presents baseline and prospective data from a randomized, double-blind, placebo-controlled trial of the safety, immunogenicity, and efficacy of the quadrivalent HPV (Type 6/11/16/18) vaccine in women ages 24 to 45.We present the results of an epidemiologic analysis of 3730 women enrolled in a quadrivalent HPV vaccine efficacy trial between June 18, 2004 and April 30, 2008. Subjects were enrolled from 7 countries (Colombia, France, Germany, Philippines, Spain, Thailand, and the United States) through community and academic health centers and primary health care providers.Average baseline prevalence of anogenital infection and/or seropositivity was 32.8% for ≥1 vaccine HPV types and 0.3% for all vaccine HPV types. Incidence of anogential infection with any vaccine HPV type was ∼10.5%. The rate of persistent infection was ∼5% over a 30-month period among women in the placebo arm naïve to the relevant type at baseline. Predictors of incident infection included younger age, marital status other than first marriage, higher number of lifetime and recent sex partners, and Chlamydia/gonorrhea infection at baseline.These findings indicate that women up to age 45 are susceptible to vaccine HPV types and some are acquiring anogenital infections with vaccine HPV types. Future study concerning incident and prevalent HPV infection among women up to age 45 is warranted (Trial NCT number NCT00090220).