Zhu Feng-Cai, Chen Wen, Hu Yue-Mei, Hong Ying, Li Juan, Zhang Xun, Zhang Yi-Ju, Pan Qin-Jing, Zhao Fang-Hui, Yu Jia-Xi, Zhang Yan-Shu, Yang Xiaoping, Zhang Cheng-Fu, Tang Haiwen, Zhang Helen, Lebacq Marie, David Marie-Pierre, Datta Sanjoy K, Struyf Frank, Bi Dan, Descamps Dominique
Jiangsu Province Center for Disease Prevention and Control, Nanjing, China.
Int J Cancer. 2014 Dec 1;135(11):2612-22. doi: 10.1002/ijc.28897. Epub 2014 May 20.
This phase II/III, double-blind, randomized trial assessed the efficacy, immunogenicity and safety of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in young Chinese women (ClinicalTrials.gov registration NCT00779766). Women aged 18-25 years from Jiangsu province were randomized (1:1) to receive HPV vaccine (n = 3,026) or Al(OH)3 control (n = 3,025) at months 0, 1 and 6. The primary objective was vaccine efficacy (VE) against HPV-16/18 associated 6-month persistent infection (PI) and/or cervical intraepithelial neoplasia (CIN) 1+. Secondary objectives were VE against virological and clinical endpoints associated with HPV-16/18 and with high-risk HPV types, immunogenicity and safety. Mean follow-up for the according-to-protocol cohort for efficacy (ATP-E) was ∼15 months after the third dose. In the ATP-E (vaccine = 2,889; control = 2,894), for initially HPV DNA negative and seronegative subjects, HPV-16/18 related VE (95% CI) was 94.2% (62.7, 99.9) against 6-month PI and/or CIN1+ and 93.8% (60.2, 99.9) against cytological abnormalities. VE against HPV-16/18 associated CIN1+ and CIN2+ was 100% (-50.4, 100) and 100% (-140.2, 100), respectively (no cases in the vaccine group and 4 CIN1+ and 3 CIN2+ cases in the control group). At Month 7, at least 99.7% of initially seronegative vaccine recipients had seroconverted for HPV-16/18; geometric mean antibody titres (95% CI) were 6,996 (6,212 to 7,880) EU/mL for anti-HPV-16 and 3,309 (2,942 to 3,723) EU/mL for anti-HPV-18. Safety outcomes between groups were generally similar. The HPV-16/18 AS04-adjuvanted vaccine is effective, immunogenic and has a clinically acceptable safety profile in young Chinese women. Prophylactic HPV vaccination has the potential to substantially reduce the burden of cervical cancer in China.
这项II/III期双盲随机试验评估了人乳头瘤病毒（HPV）16/18 AS04佐剂疫苗在年轻中国女性中的疗效、免疫原性和安全性（ClinicalTrials.gov注册号NCT00779766）。来自江苏省的18至25岁女性被随机分组（1:1），在第0、1和6个月分别接受HPV疫苗（n = 3026）或氢氧化铝对照剂（n = 3025）。主要目标是疫苗针对HPV-16/18相关的6个月持续感染（PI）和/或宫颈上皮内瘤变（CIN）1+的效力（VE）。次要目标是针对与HPV-16/18以及高危HPV类型相关的病毒学和临床终点的VE、免疫原性和安全性。按方案进行疗效评估的队列（ATP-E）在第三次给药后平均随访约15个月。在ATP-E组（疫苗组 = 2889；对照组 = 2894）中，对于最初HPV DNA阴性且血清学阴性的受试者，HPV-16/18相关的VE（95% CI）针对6个月PI和/或CIN1+为94.2%（62.7，99.9），针对细胞学异常为93.8%（60.2，99.9）。针对HPV-16/18相关CIN1+和CIN2+的VE分别为100%（-50.4，100）和100%（-140.2，100）（疫苗组无病例，对照组有4例CIN1+和3例CIN2+病例）。在第7个月，至少99.7%最初血清学阴性的疫苗接种者针对HPV-16/18发生了血清转化；抗HPV-16的几何平均抗体滴度（95% CI）为6996（6212至7880）EU/mL，抗HPV-18为3309（2942至3723）EU/mL。两组间的安全性结果总体相似。HPV-16/18 AS04佐剂疫苗在年轻中国女性中有效、具有免疫原性且具有临床可接受的安全性。预防性HPV疫苗接种有可能大幅减轻中国宫颈癌的负担。
