3). Open in a separate window Fig. on a protocol-specified algorithm. External genital and cervical biopsies of abnormal lesions were performed, and histological diagnoses were adjudicated by a pathology panel. Specimens were tested by PCR to detect HPV DNA. Results Geometric mean titers for each 9vHPV vaccine HPV type peaked around month 7 and gradually decreased through month 90. Seropositivity rates remained 90% through month 90 for each of the 9vHPV vaccine types by HPV immunoglobulin Luminex Immunoassay. No cases of HPV6/11/16/18/31/33/45/52/58-related high-grade intraepithelial neoplasia or mogroside IIIe genital warts were observed in the per-protocol populace (n?=?1107) based on a maximum follow-up of 8.2 years (median mogroside IIIe 7.6 years) post-Dose 3. Incidence rates of HPV6/11/16/18/31/33/45/52/58-related 6-month persistent contamination in females and males were 49.2 and 37.3 per 10,000 person-years, respectively, which were within ranges expected in vaccinated cohorts. There were no vaccine-related SAEs or deaths during the period covered by this interim analysis. Conclusions The 9vHPV vaccine provided sustained immunogenicity and durable effectiveness through approximately 7 and 8 years, respectively, following vaccination of girls and boys aged 9C15 years. strong class=”kwd-title” Keywords: Nine-valent human papillomavirus vaccine, Effectiveness, Immunogenicity, Long-term follow-up strong class=”kwd-title” Abbreviations: 9vHPV, nine-valent human papillomavirus; AIS, adenocarcinoma in situ; bHPV, bivalent human papillomavirus; BMI, body mass index; CI, confidence interval; CIN, cervical intraepithelial neoplasia; cLIA, competitive Luminex Immunoassay; EEC, endo-/ectocervical; GMT, geometric mean titer; HN-TS, HPV-na?ve, type-specific; HPV, human papillomavirus; IgG-LIA, immunoglobulin G Luminex Immunoassay; LTFU, long-term follow-up; LVPP, labial/vulvar/perineal/perianal; DDR1 PCR, polymerase chain reaction; PIN, penile intraepithelial neoplasia; PPE, per-protocol effectiveness; PPI, per-protocol immunogenicity; qHPV, quadrivalent human papillomavirus; SAE, serious adverse event; SD, standard deviation; VaIN, vaginal intraepithelial neoplasia; VIN, vulvar intraepithelial neoplasia; WHO, World Health Business 1.?Introduction The nine-valent human papillomavirus (9vHPV) vaccine was developed mogroside IIIe to prevent contamination with seven oncogenic HPV types (HPV16/18/31/33/45/52/58) that together account for approximately 90% of cervical cancers and HPV-related vulvar, vaginal, and anal cancers, and two HPV types (HPV6/11) that are responsible for approximately 90% of genital warts [[1], [2], [3], [4]]. In the pivotal efficacy trial in young women aged 16C26 years (Study V503-001; “type”:”clinical-trial”,”attrs”:”text”:”NCT00543543″,”term_id”:”NCT00543543″NCT00543543), the 9vHPV vaccine exhibited efficacy in preventing persistent contamination and disease related to those HPV types covered by the 9vHPV vaccine [[5], [6], [7]]. The vaccine also elicited strong and persistent antibody responses to all nine HPV types in young women through 5 years post-vaccination [5]. While adults remain at risk for HPV contamination throughout their lives, HPV is usually often acquired soon after sexual debut [8]. As such, HPV vaccination should target individuals prior to sexual debut for maximal benefit. An immunogenicity and safety study (Study V503-002; “type”:”clinical-trial”,”attrs”:”text”:”NCT00943722″,”term_id”:”NCT00943722″NCT00943722) was conducted in girls and boys aged 9C15 years who were given three doses of the 9vHPV vaccine (at day 1 and months 2 and 6) [9,10]. At 4 weeks post-Dose 3, HPV antibody responses in girls and boys aged 9C15 years mogroside IIIe were non-inferior compared with those in young women aged 16C26 years; based on these results, vaccine efficacy previously established in young women [5,6] was inferred for the younger age groups [9]. In addition, the HPV antibody responses persisted through 2.5 years post-Dose 3 and the vaccine was generally well tolerated throughout the entire study [9]. mogroside IIIe Given that the risk of HPV contamination is lifelong, the benefits of HPV vaccination will be fully realized if the protection is usually long-lasting. Therefore, the World Health Business (WHO) has decided that long-term follow-up (LTFU) studies to assess long-term efficacy, safety, and immunogenicity should be an integral part of prophylactic HPV-vaccine development [11]. An LTFU study of the quadrivalent HPV (qHPV) vaccine has previously demonstrated durable effectiveness and sustained immunogenicity when given to girls and boys aged 9C15 years through 10 years post-vaccination [12]. Likewise, an LTFU study of the bivalent HPV (bHPV).