Open AccessEfficacy, 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
Author(s) -
Zhu Fengcai,
Hu ShangYing,
Hong Ying,
Hu YueMei,
Zhang Xun,
Zhang YiJu,
Pan QinJing,
Zhang WenHua,
Zhao FangHui,
Zhang ChengFu,
Yang Xiaoping,
Yu JiaXi,
Zhu Jiahong,
Zhu Yejiang,
Chen Feng,
Zhang Qian,
Wang Hong,
Wang Changrong,
Bi Jun,
Xue Shiyin,
Shen Lingling,
Zhang YanShu,
He Yunkun,
Tang Haiwen,
Karkada Naveen,
Suryakiran Pemmaraju,
Bi Dan,
Struyf Frank
Publication year - 2017
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.869
Subject(s) - immunogenicity , medicine , adverse effect , confidence interval , randomized controlled trial , hpv vaccines , cohort , titer , vaccination , vaccine efficacy , antibody titer , hpv infection , antibody , immunology , cervical cancer , cancer
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.