双价人乳头瘤病毒疫苗(大肠杆菌)的有效性研究:一项随机对照临床试验的中期分析

Efficacy of an Escherichia coli-produced bivalent human papillomavirus vaccine: an interim analysis of a randomized clinical trial

目的评价一种新型双价人乳头瘤病毒(HPV)疫苗(大肠杆菌)的有效性。方法采用多中心、随机、双盲设计,自2012年11月至2013年4月在中国5个地区入组18~45岁健康女性,按年龄分层(18~26岁组、27~45岁组)后进行区组(12个疫苗编号为一区组)随机,按1∶1比例分配至研究组(双价HPV疫苗)或对照组(戊型肝炎疫苗),按照0、1、6月三针免疫程序接种。主要终点为分析疫苗对HPV16和(或)HPV18相关的高级别生殖器癌前病变和HPV持续感染(6个月以上)。结果共入组7 372名女性,其中研究组3 689人,对照组3 683人,平均随访3.3年。在符合方案人群中,对于预防HPV16和(或)HPV18相关的高级别宫颈上皮内病变、原位腺癌和宫颈癌和HPV持续感染的有效性分别为100%(95%CI:55.6%~100%)和97.8%(95%CI:87.1%~99.9%)。疫苗的安全性良好(单独著文报道)。结论双价人乳头瘤病毒疫苗(大肠杆菌)能够有效预防HPV16和(或)HPV18相关的高级别生殖器癌前病变和HPV持续感染。

Objective To evaluate the efficacy of a novel Escherichia coli-produced bivalent HPV16/18 vaccine. Methods A multicenter, randomized, double-blind trial was conducted in five sites started from November 2012 to April 2013 in China. In total, eligible women aged 18~45 years were age-stratified(into two groups:18~26 and 27~45 years) and randomly assigned(1∶1) according to a permuted block randomization list(with 12 codes per block) to receive three doses of the test or control(hepatitis E) vaccine at months 0, 1, and 6. The primary endpoints included high-grade genital lesions and persistent infection(over 6 months) associated with HPV16/18. Results Totally 7 372 healthy women were randomly assigned to the test group(3 689) and placebo group(3 683), and were followed for an average of 3.3 years. In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0%(95% confidence interval=55.6% to 100.0%, and 97.8%(95% confidence interval=87.1% to 99.9%), respectively. The vaccine was well tolerated. Conclusions The E. coli-produced HPV16/18 vaccine is well tolerated and highly efficacious against HPV16/18–associated high-grade genital lesions and persistent infection in women.