Background: The pivotal Phase III immunogenicity study of the 9vHPV vaccine in girls and boys (age 9-15 years) was extended to assess long-term immunogenicity and effectiveness through 10 years post-dose 3. We describe the first interim analysis at month 72. Subsequent analyses are planned at months 96 and 126, respectively. Methods: Overall, 1272 subjects (971 females, 301 males) who received 3 doses of 9vHPV vaccine at day 1 and months 2 and 6 were enrolled in the study extension. Serum was collected at month 66 to assess antibody responses. Starting at age 16 years, genital swabs were collected every 6 months and tested by PCR to detect HPV DNA. Pap tests were collected annually in female subjects starting at age 21 years. External genital and cervical biopsies on abnormal lesions were performed as indicated in the protocol. Tissue samples were adjudicated by a pathology panel and tested by PCR to detect HPV DNA. Results: Geometric mean titers peaked around month 7 and gradually decreased through month 66, consistent with observed immunogenicity profile in previous studies of the 9vHPV vaccine. Seropositivity rates remained >90% through month 66 for each of the 9vHPV vaccine types. No cases of HPV 6/11/16/18/31/33/45/52/58-related disease (cervical/vulvar/vaginal lesions and genital warts in females, external genital lesions and genital warts in males) were observed in the per-protocol population (maximum follow-up: 6.4 years [median 5.9 years] post-dose 3). Incidence rates of HPV6/11/16/18/31/33/45/52/58-related 6-month persistent infection in females and males were low (20.3 and 24.3 per 10,000 person-years, respectively) and within ranges expected in vaccinated cohorts (based on results from efficacy trials of 4-valent and 9-valent HPV vaccines). Conclusions: This analysis demonstrates sustained immunogenicity through 5 years post-vaccination and durable effectiveness through 6 years post-vaccination in girls and boys aged 9-15 years.