title: Efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine in Chinese women aged 18-25 years: event-triggered analysis of a randomized controlled trial.
abstract: We previously reported the results of a phase II/III, double-blind, randomized controlled study in Chinese women (NCT00779766) showing a 94.2% (95% confidence interval: 62.7-99.9) HPV-16/18 AS04-adjuvanted vaccine efficacy (VE) against cervical intraepithelial neoplasia grade 1 or higher (CIN1+) and/or 6-month (M) persistent infection (PI) with a mean follow-up of <2 years, and immunogenicity until 7 months post-dose 1. Here, we report efficacy and safety results from an event-triggered analysis with ~3 years longer follow-up, and immunogenicity until M24. Healthy 18-25-year-old women (N = 6051) were randomized (1:1) to receive three doses of HPV-16/18 vaccine or Al(OH)3(control) at M0, 1, 6. VE against HPV-16/18-associated CIN2+, and cross-protective VE against infections with nonvaccine oncogenic HPV types, immunogenicity, and safety were assessed. In the according-to-protocol efficacy cohort, in initially seronegative/DNA-negative women (vaccine group: N = 2524; control group: N = 2535), VE against HPV-16/18-associated CIN2+ was 87.3% (5.3-99.7); VE against incident infection or against 6-month persistent infection associated with HPV-31/33/45 was 50.1% (34.3-62.3) or 52.6% (24.5-70.9), respectively. At least, 99.6% of HPV-16/18-vaccines remained seropositive for anti-HPV-16/18 antibodies; anti-HPV-16 and -18 geometric mean titers were 1271.1 EU/mL (1135.8-1422.6) and 710.0 EU/ml (628.6-801.9), respectively. Serious adverse events were infrequent (1.7% vaccine group [N = 3026]; 2.5% control group [N = 3026]). Of the 1595 reported pregnancies, nine had congenital anomalies (five live infants, three elective terminations, one stillbirth) that were unlikely vaccination-related (blinded data). VE against HPV-16/18-associated CIN2+ was demonstrated and evidence of cross-protective VE against oncogenic HPV types was shown. The vaccine was immunogenic and had an acceptable safety profile.
authors.affiliation: Jiangsu Province Center for Disease Prevention and Control, Nanjing, China.
authors.forename: Feng-Cai
authors.initials: FC
authors.lastname: Zhu
authors.affiliation: National Cancer Center - Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China.
authors.forename: Shang-Ying
authors.initials: SY
authors.lastname: Hu
authors.affiliation: Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Jiangsu Province Center for Disease Prevention and Control, Nanjing, China.
authors.forename: Yue-Mei
authors.initials: YM
authors.lastname: Hu
authors.affiliation: National Cancer Center - Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Jiangsu Province Center for Disease Prevention and Control, Nanjing, China.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: National Cancer Center - Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China.
authors.forename: Qin-Jing
authors.initials: QJ
authors.lastname: Pan
authors.affiliation: National Cancer Center - Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China.
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Zhang
authors.affiliation: National Cancer Center - Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China.
authors.forename: Fang-Hui
authors.initials: FH
authors.lastname: Zhao
authors.affiliation: Lianshui Center for Disease Prevention and Control, Lianshui, China.
authors.forename: Cheng-Fu
authors.initials: CF
authors.lastname: Zhang
authors.affiliation: Jintan Center for Disease Prevention and Control, Jintan, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Yang
authors.affiliation: Xuzhou Center for Disease Prevention and Control, Xuzhou, China.
authors.forename: Jia-Xi
authors.initials: JX
authors.lastname: Yu
authors.affiliation: Lianshui Center for Disease Prevention and Control, Lianshui, China.
authors.forename: Jiahong
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Binhai Center for Disease Prevention and Control, Yancheng, China.
authors.forename: Yejiang
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: National Cancer Center - Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: National Cancer Center - Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: National Cancer Center - Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Jintan Center for Disease Prevention and Control, Jintan, China.
authors.forename: Changrong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Xuzhou Center for Disease Prevention and Control, Xuzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Bi
authors.affiliation: Lianshui Center for Disease Prevention and Control, Lianshui, China.
authors.forename: Shiyin
authors.initials: S
authors.lastname: Xue
authors.affiliation: Xuzhou Center for Disease Prevention and Control, Xuzhou, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Shen
authors.affiliation: Binhai Center for Disease Prevention and Control, Yancheng, China.
authors.forename: Yan-Shu
authors.initials: YS
authors.lastname: Zhang
authors.affiliation: GSK Vaccines, Shanghai, China.
authors.forename: Yunkun
authors.initials: Y
authors.lastname: He
authors.affiliation: GSK Vaccines, Shanghai, China.
authors.forename: Haiwen
authors.initials: H
authors.lastname: Tang
authors.affiliation: GSK Pharmaceuticals India Ltd, Bangalore, India.
authors.forename: Naveen
authors.initials: N
authors.lastname: Karkada
authors.affiliation: GSK Pharmaceuticals India Ltd, Bangalore, India.
authors.forename: Pemmaraju
authors.initials: P
authors.lastname: Suryakiran
authors.affiliation: GSK Vaccines, Wavre, Belgium.
authors.forename: Dan
authors.initials: D
authors.lastname: Bi
authors.affiliation: GSK Vaccines, Wavre, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Struyf
mesh_terms: D000914:Antibodies, Viral / Q000097:blood*; D002681:China; D004311:Double-Blind Method; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D052161:Human papillomavirus 18 / Q000276:immunology*; D006801:Humans; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18
keywords: Efficacy; HPV-16/18 AS04-adjuvanted vaccine; human papillomavirus; immunogenicity; safety