Study Objective: To compare the prevalence of human papillomavirus (HPV) genital infection among prepubertal children, sexually active and not sexually active adolescents, and assess potential risk factors for transmission. Design: Prospective study. Setting: Outpatient adolescent health clinic. Participants: Ninety-five girls aged 2-21 years; 38 sexually active adolescents (group A), 28 not sexually active adolescents (group B), and 29 prepubertal children (group C). Interventions: Participants' vaginal or cervical specimens were tested for HPV with the CLART HPV 2 assay (Clinical Array Technology, Genomica, Madrid, Spain) and for cytological abnormalities with liquid-based cytology. Main Outcome Measures: Differences in prevalence of low- and high-risk HPV infections among the 3 groups. Results: Genital HPV was detected in 37.9% (36/95) of all participants; 47.4% (18/38) of group A, 28.6% (8/28) of group B, and 34.5% (10/29)of group C (P = .27). Multiple HPV infection was detected in 26.3% (10/38), 10.7% (3/28), and 13.8% (4/29) of groups A, B, and C, respectively (P = .21). High-risk genotypes were detected in 47.4% (18/38), 28.6% (8/28), and 24.1% (7/29) of groups A, B, and C, respectively (P = .10). Main high-risk genotypes were HPV 16 (27%, 10/37), HPV 31 (21.6%, 8/37), HPV 35 (13.5%, 5/37), HPV 53 (13.5%, 5/37), and low-risk HPV 6 (18.9%, 7/37). Sexual activity was associated with increased risk for genital high-risk HPV infection (odds ratio = 3.41; 95% confidence interval, 1.19-9.78); specifically with HPV 33 and HPV 51. Forty percent of sexually active adolescents with normal cervical cytology were infected with high-risk HPV types. Family history of skin HPV was positively associated with genital HPV in the sexually active group (odds ratio = 2.01; 95% confidence interval, 1.17-3.46). Conclusion: Timeline and target population for HPV vaccination might need to be reappraised, in view of significant nonsexual transmission of genital HPV so early in childhood.