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We performed a study to better characterize the natural history of genital human papillomavirus (HPV) infection in a cohort of closely followed adolescent women.A cohort of 60 adolescent women was followed over a 2.2-year period, on average. A median of 41.5 self-collected vaginal and clinician-obtained cervical swabs were obtained from each subjectHPV was detected in 45.3% of all adequate specimens, by use of a polymerase chain reaction/reverse blot strip assay. Oncogenic—or high-risk (HR)—HPV types were detected in 38.6% of specimens, and nononcogenic—or low-risk (LR)—types were detected in 19.6% of specimens. During the entire study period, 49 of 60 subjects tested positive for HPV (cumulative prevalence, 81.7%). The most frequently detected HR types were HPV types 52, 16, and 59. Infections with multiple HPV types were common. The median duration of persistence of a specific HPV type was 168 days, and HR types were more persistent than LR types. Abnormal cervical cytological results occurred in 37% of the adolescent women and were significantly associated with HR HPV infection.The cumulative prevalence of HPV infection in sexually active adolescent women is extremely high, involves numerous HPV types, and frequently results in cervical dysplasia.