九价人乳头瘤病毒疫苗预防女性感染和上皮内瘤变。
A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women.
机构信息
From the Medical University of Vienna, Comprehensive Cancer Center, Vienna (E.A.J.); Moffitt Cancer Center, Tampa, FL (A.R.G.); Department of Clinical Medicine, University of Bergen-Haukeland University Hospital, Bergen, Norway (O.-E.I.); Université Laval, Québec, QC (C.B.), and University of British Columbia, Vancouver (G.S.) - both in Canada; University of Washington, Seattle (C.M.); Coordinating Research Center, Frederiksberg Hospital, University of Copenhagen (J.M.), and Danish Cancer Society Research Center and Department of Gynecology, Rigshospitalet (S.K.K.) - all in Copenhagen; Associação Obras Sociais Irmã Dulce and Oswaldo Cruz Foundation, Brazilian Ministry of Health, Bahia, Brazil (E.D.M.); University of Hong Kong, Hong Kong (Y.N.); Aarhus University Hospital, Department of Obstetrics and Gynecology, Aarhus, Denmark (L.K.P.); Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico (E.L.-P.); Faculty of Tropical Medicine, Mahidol University, Nakhon Pathom, Thailand (P.P.); Investigación Clínica, Medellín, Colombia (J.A.R.); Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (L.W.); Mackay Memorial Hospital, Taipei, Taiwan (Y.C.Y.); Wolfson Institute of Preventive Medicine, London (J. Cuzick); Royal Women's Hospital, University of Melbourne and Murdoch Childrens Research Institute, Parkville, VIC, Australia (S.M.G.); Division of Gynecologic Oncology, University of Alabama, Birmingham (W.H.); and Merck, Whitehouse Station, NJ (O.M.B., I.S.F.C., J. Chen, R.G., E.M., M.R., S.V., A.L.).
出版信息
N Engl J Med. 2015 Feb 19;372(8):711-23. doi: 10.1056/NEJMoa1405044.
BACKGROUND
The investigational 9-valent viruslike particle vaccine against human papillomavirus (HPV) includes the HPV types in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58). Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age.
METHODS
We performed a randomized, international, double-blind, phase 2b-3 study of the 9vHPV vaccine in 14,215 women. Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6. Serum was collected for analysis of antibody responses. Swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue were obtained and used for HPV DNA testing, and liquid-based cytologic testing (Papanicolaou testing) was performed regularly. Tissue obtained by means of biopsy or as part of definitive therapy (including a loop electrosurgical excision procedure and conization) was tested for HPV.
RESULTS
The rate of high-grade cervical, vulvar, or vaginal disease irrespective of HPV type (i.e., disease caused by HPV types included in the 9vHPV vaccine and those not included) in the modified intention-to-treat population (which included participants with and those without prevalent infection or disease) was 14.0 per 1000 person-years in both vaccine groups. The rate of high-grade cervical, vulvar, or vaginal disease related to HPV-31, 33, 45, 52, and 58 in a prespecified per-protocol efficacy population (susceptible population) was 0.1 per 1000 person-years in the 9vHPV group and 1.6 per 1000 person-years in the qHPV group (efficacy of the 9vHPV vaccine, 96.7%; 95% confidence interval, 80.9 to 99.8). Antibody responses to HPV-6, 11, 16, and 18 were noninferior to those generated by the qHPV vaccine. Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group.
CONCLUSIONS
The 9vHPV vaccine prevented infection and disease related to HPV-31, 33, 45, 52, and 58 in a susceptible population and generated an antibody response to HPV-6, 11, 16, and 18 that was noninferior to that generated by the qHPV vaccine. The 9vHPV vaccine did not prevent infection and disease related to HPV types beyond the nine types covered by the vaccine. (Funded by Merck; ClinicalTrials.gov number, NCT00543543).
背景
针对人类乳头瘤病毒（HPV）的九价病毒样颗粒疫苗包括了四价 HPV 疫苗（HPV6、HPV11、HPV16 和 HPV18）中的 HPV 类型以及另外五种致癌类型（HPV31、HPV33、HPV45、HPV52 和 HPV58）。在此，我们报告了九价 HPV 疫苗在 16-26 岁女性中的疗效和免疫原性研究结果。
方法
我们进行了一项国际性、随机、双盲、2b-3 期临床试验，评估九价 HPV 疫苗在 14215 名女性中的效果。参与者按计划于第 1 天和第 2 个月、第 6 个月接受三剂九价 HPV 疫苗或四价 HPV 疫苗的肌内注射。采集血清以分析抗体应答。采集阴唇、外阴、会阴、肛周、宫颈和阴道的拭子，进行 HPV DNA 检测和液基细胞学检测（巴氏涂片检测）。对活检或作为明确治疗一部分（包括环形电切术和锥切术）获得的组织进行 HPV 检测。
结果
在改良意向治疗人群（包括有和无现患感染或疾病的参与者）中，不论 HPV 类型（即九价 HPV 疫苗包含的 HPV 类型和不包含的 HPV 类型引起的疾病），高级别宫颈、外阴或阴道疾病的发生率在两组疫苗中均为每 1000 人年 14.0 例。在特定的符合方案疗效人群（易感人群）中，九价 HPV 疫苗组中与 HPV-31、HPV33、HPV45、HPV52 和 HPV58 相关的高级别宫颈、外阴或阴道疾病的发生率为每 1000 人年 0.1 例，四价 HPV 疫苗组为每 1000 人年 1.6 例（九价 HPV 疫苗的疗效为 96.7%；95%置信区间为 80.9 至 99.8）。HPV-6、HPV11、HPV16 和 HPV18 的抗体应答与四价 HPV 疫苗相当。九价 HPV 疫苗组的注射部位相关不良事件发生率高于四价 HPV 疫苗组。
结论
九价 HPV 疫苗预防了易感人群中与 HPV-31、HPV33、HPV45、HPV52 和 HPV58 相关的感染和疾病，并产生了与四价 HPV 疫苗相当的 HPV-6、HPV11、HPV16 和 HPV18 的抗体应答。九价 HPV 疫苗不能预防疫苗覆盖的九种类型以外的 HPV 类型引起的感染和疾病。（由默克公司资助；临床试验编号，NCT00543543）。
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