24至45岁女性四价人乳头瘤病毒（6、11、16、18型）重组疫苗的安全性、免疫原性及有效性：一项随机双盲试验

Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24-45 years: a randomised, double-blind trial.

作者信息

Muñoz Nubia, Manalastas Ricardo, Pitisuttithum Punee, Tresukosol Damrong, Monsonego Joseph, Ault Kevin, Clavel Christine, Luna Joaquin, Myers Evan, Hood Sara, Bautista Oliver, Bryan Janine, Taddeo Frank J, Esser Mark T, Vuocolo Scott, Haupt Richard M, Barr Eliav, Saah Alfred

机构信息

National Institute of Cancer, Bogotá, Colombia.

出版信息

Lancet. 2009 Jun 6;373(9679):1949-57. doi: 10.1016/S0140-6736(09)60691-7. Epub 2009 Jun 1.

DOI:10.1016/S0140-6736(09)60691-7

PMID:19493565

Abstract

BACKGROUND

Although the peak incidence of human papillomavirus (HPV) infection occurs in most populations within 5-10 years of first sexual experience, all women remain at risk for acquisition of HPV infections. We tested the safety, immunogenicity, and efficacy of the quadrivalent HPV (types 6, 11, 16, 18) L1 virus-like-particle vaccine in women aged 24-45 years.

METHODS

Women aged 24-45 years with no history of genital warts or cervical disease were enrolled from community health centres, academic health centres, and primary health-care providers into an ongoing multicentre, parallel, randomised, placebo-controlled, double-blind study. Participants were allocated by computer-generated schedule to receive quadrivalent HPV vaccine (n=1911) or placebo (n=1908) at day 1, and months 2 and 6. All study site investigators and personnel, study participants, monitors, and central laboratory personnel were blinded to treatment allocation. Coprimary efficacy endpoints were 6 months' or more duration of infection and cervical and external genital disease due to HPV 6, 11, 16, 18; and due to HPV 16 and 18 alone. Primary efficacy analyses were done in a per-protocol population, but intention-to-treat analyses were also undertaken. This study is registered with ClinicalTrials.gov, number NCT00090220.

FINDINGS

1910 women received at least one dose of vaccine and 1907 at least one dose of placebo. In the per-protocol population, efficacy against the first coprimary endpoint (disease or infection related to HPV 6, 11, 16, and 18) was 90.5% (95% CI 73.7-97.5, four of 1615 cases in the vaccine group vs 41/1607 in the placebo group) and 83.1% (50.6-95.8, four of 1601 cases vs 23/1579 cases) against the second coprimary endpoint (disease or infection related to HPV 16 and 18 alone). In the intention-to-treat population, efficacy against the first coprimary endpoint was 30.9% (95% CI 11.1-46.5, 108/1886 cases vs 154/1883 cases) and against the second coprimary endpoint was 22.6% (-2.9 to 41.9, 90/1886 cases vs 115/1883 cases), since infection and disease were present at baseline. We recorded no vaccine-related serious adverse events.

INTERPRETATION

The quadrivalent HPV vaccine is efficacious in women aged 24-45 years not infected with the relevant HPV types at enrolment.

FUNDING

Merck (USA).

摘要

背景

虽然大多数人群中人乳头瘤病毒（HPV）感染的高峰发病率出现在首次性行为后的5至10年内，但所有女性仍有感染HPV的风险。我们测试了四价HPV（6、11、16、18型）L1病毒样颗粒疫苗在24至45岁女性中的安全性、免疫原性和有效性。

方法

从社区卫生中心、学术健康中心和初级卫生保健机构招募24至45岁无尖锐湿疣或宫颈疾病史的女性，纳入一项正在进行的多中心、平行、随机、安慰剂对照、双盲研究。参与者通过计算机生成的时间表分配，在第1天、第2个月和第6个月接受四价HPV疫苗（n = 1911）或安慰剂（n = 1908）。所有研究地点的调查人员和工作人员、研究参与者、监测人员和中央实验室人员均对治疗分配不知情。共同主要疗效终点为因HPV 6、11、16、18型以及仅因HPV 16和18型导致的6个月或更长时间的感染以及宫颈和外生殖器疾病。主要疗效分析在符合方案人群中进行，但也进行了意向性分析。本研究已在ClinicalTrials.gov注册，编号为NCT00090220。

结果

1910名女性接受了至少一剂疫苗，1907名女性接受了至少一剂安慰剂。在符合方案人群中，针对第一个共同主要终点（与HPV 6、11、16和18型相关的疾病或感染）的疗效为90.5%（95%CI 73.7 - 97.5，疫苗组1615例中有4例，安慰剂组1607例中有41例），针对第二个共同主要终点（仅与HPV 16和18型相关的疾病或感染）的疗效为83.1%（50.6 - 95.8，1601例中有4例，1579例中有23例）。在意向性分析人群中，针对第一个共同主要终点的疗效为30.9%（95%CI 11.1 - 46.5，1886例中有108例，1883例中有154例），针对第二个共同主要终点的疗效为22.6%（-2.9至41.9，1886例中有90例，1883例中有115例），因为在基线时就存在感染和疾病。我们未记录到与疫苗相关的严重不良事件。