Beachler Daniel C, Kreimer Aimée R, Schiffman Mark, Herrero Rolando, Wacholder Sholom, Rodriguez Ana Cecilia, Lowy Douglas R, Porras Carolina, Schiller John T, Quint Wim, Jimenez Silvia, Safaeian Mahboobeh, Struijk Linda, Schussler John, Hildesheim Allan, Gonzalez Paula
Division of Cancer Epidemiology, and Genetics (DCB, ARK, MS, SW, MS, AH) and Center for Cancer Research (DRL, JTS), National Cancer Institute, NIH, Bethesda, MD; Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Costa Rica (RH, ACR, CP, SJ, PG); Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon, France (RH); DDL Diagnostic Laboratory, Voorburg, the Netherlands (WQ, LS); Information Management Systems, Rockville, MD (JS).
J Natl Cancer Inst. 2015 Oct 14;108(1). doi: 10.1093/jnci/djv302. Print 2016 Jan.
Previous Costa Rica Vaccine Trial (CVT) reports separately demonstrated vaccine efficacy against HPV16 and HPV18 (HPV16/18) infections at the cervical, anal, and oral regions; however, the combined overall multisite efficacy (protection at all three sites) and vaccine efficacy among women infected with HPV16 or HPV18 prior to vaccination are less known.
Women age 18 to 25 years from the CVT were randomly assigned to the HPV16/18 vaccine (Cervarix) or a hepatitis A vaccine. Cervical, oral, and anal specimens were collected at the four-year follow-up visit from 4186 women. Multisite and single-site vaccine efficacies (VEs) and 95% confidence intervals (CIs) were computed for one-time detection of point prevalent HPV16/18 in the cervical, anal, and oral regions four years after vaccination. All statistical tests were two-sided.
The multisite woman-level vaccine efficacy was highest among "naïve" women (HPV16/18 seronegative and cervical HPV high-risk DNA negative at vaccination) (vaccine efficacy = 83.5%, 95% CI = 72.1% to 90.8%). Multisite woman-level vaccine efficacy was also demonstrated among women with evidence of a pre-enrollment HPV16 or HPV18 infection (seropositive for HPV16 and/or HPV18 but cervical HPV16/18 DNA negative at vaccination) (vaccine efficacy = 57.8%, 95% CI = 34.4% to 73.4%), but not in those with cervical HPV16 and/or HPV18 DNA at vaccination (anal/oral HPV16/18 VE = 25.3%, 95% CI = -40.4% to 61.1%). Concordant HPV16/18 infections at two or three sites were also less common in HPV16/18-infected women in the HPV vaccine vs control arm (7.4% vs 30.4%, P < .001).
This study found high multisite vaccine efficacy among "naïve" women and also suggests the vaccine may provide protection against HPV16/18 infections at one or more anatomic sites among some women infected with these types prior to HPV16/18 vaccination.
先前的哥斯达黎加疫苗试验(CVT)报告分别证明了疫苗对子宫颈、肛门和口腔区域的人乳头瘤病毒16型和18型(HPV16/18)感染的效力;然而,联合的总体多部位效力(在所有三个部位的保护作用)以及在接种疫苗前感染HPV16或HPV18的女性中的疫苗效力尚鲜为人知。
来自CVT的18至25岁女性被随机分配至HPV16/18疫苗(希瑞适)组或甲型肝炎疫苗组。在4186名女性的四年随访访视时收集子宫颈、口腔和肛门标本。计算接种疫苗四年后子宫颈、肛门和口腔区域点流行HPV16/18一次性检测的多部位和单部位疫苗效力(VE)及95%置信区间(CI)。所有统计检验均为双侧检验。
多部位女性水平的疫苗效力在“未感染”女性(接种疫苗时HPV16/18血清阴性且子宫颈HPV高危DNA阴性)中最高(疫苗效力 = 83.5%,95%CI = 72.1%至90.8%)。在有接种前HPV16或HPV18感染证据的女性(HPV16和/或HPV18血清阳性但接种疫苗时子宫颈HPV16/18 DNA阴性)中也证明有多部位女性水平的疫苗效力(疫苗效力 = 57.8%,95%CI = 34.4%至73.4%),但在接种疫苗时子宫颈有HPV16和/或HPV18 DNA的女性中未观察到(肛门/口腔HPV16/18 VE = 25.3%,95%CI = -40.4%至61.1%)。在HPV疫苗组与对照组中,HPV16/18感染的女性中两个或三个部位一致的HPV16/18感染也较少见(7.4%对30.4%,P <.001)。
本研究在“未感染”女性中发现了较高的多部位疫苗效力,并且还表明该疫苗可能为在HPV16/18疫苗接种前感染这些类型病毒的一些女性提供针对一个或多个解剖部位HPV16/18感染的保护。