Hildesheim Allan, Wacholder Sholom, Catteau Gregory, Struyf Frank, Dubin Gary, Herrero Rolando
National Cancer Institute (NCI), Division of Cancer Epidemiology and Genetics, 9609 Medical Center Drive, Bethesda, MD 20892, United States.
GlaxoSmithKline Vaccines, Avenue Fleming 20, B-1300 Wavre, Belgium.
Vaccine. 2014 Sep 3;32(39):5087-97. doi: 10.1016/j.vaccine.2014.06.038. Epub 2014 Jul 10.
A community-based randomized trial was conducted in Costa Rica to evaluate the HPV-16/18 AS04-adjuvanted vaccine (NCT00128661). The primary objective was to evaluate efficacy of the vaccine to prevent cervical intraepithelial neoplasia 2 or more severe disease (CIN2+) associated with incident HPV-16/18 cervical infections. Secondary objectives were to evaluate efficacy against CIN2+ associated with incident cervical infection by any oncogenic HPVs and to evaluate duration of protection against incident cervical infection with HPV-16/18. Vaccine safety and immunogenicity over the 4-year follow-up were also evaluated.
We randomized (3727 HPV arm; 3739 control arm), vaccinated (HPV-16/18 or Hepatitis A) and followed (median 53.8 months) 7466 healthy women aged 18-25 years. 5312 women (2635 HPV arm; 2677 control arm) were included in the according to protocol analysis for efficacy. The full cohort was evaluated for safety. Immunogenicity was considered on a subset of 354 (HPV-16) and 379 (HPV-18) women. HPV type was assessed by PCR on cervical specimens. Immunogenicity was assessed using ELISA and inhibition enzyme immunoassays. Disease outcomes were histologically confirmed. Vaccine efficacy and 95% confidence intervals (95%CI) were computed.
Vaccine efficacy was 89.8% (95% CI: 39.5-99.5; N=11 events total) against HPV-16/18 associated CIN2+, 59.9% (95% CI: 20.7-80.8; N=39 events total) against CIN2+ associated with non-HPV-16/18 oncogenic HPVs and 61.4% (95% CI: 29.5-79.8; N=51 events total) against CIN2+ irrespective of HPV type. The vaccine had an acceptable safety profile and induced robust and long-lasting antibody responses.
Our findings confirm the high efficacy and immunogenicity of the HPV-16/18 vaccine against incident HPV infections and cervical disease associated with HPV-16/18 and other oncogenic HPV types. These results will serve as a benchmark to which we can compare future findings from the ongoing extended follow-up of participants in the Costa Rica trial.
Registered with clinicaltrials.gov: NCT00128661.
在哥斯达黎加开展了一项基于社区的随机试验，以评估HPV-16/18 AS04佐剂疫苗（NCT00128661）。主要目标是评估该疫苗预防与HPV-16/18宫颈感染相关的宫颈上皮内瘤变2级或更严重疾病（CIN2+）的疗效。次要目标是评估针对任何致癌性人乳头瘤病毒导致的宫颈感染相关CIN2+的疗效，以及评估针对HPV-16/18宫颈感染的保护持续时间。还评估了4年随访期间疫苗的安全性和免疫原性。
我们将7466名18至25岁的健康女性随机分组（HPV组3727人；对照组3739人），进行疫苗接种（HPV-16/18或甲型肝炎疫苗）并随访（中位时间53.8个月）。5312名女性（HPV组2635人；对照组2677人）纳入符合方案疗效分析。对整个队列进行安全性评估。在354名（HPV-16）和379名（HPV-18）女性亚组中评估免疫原性。通过对宫颈标本进行PCR检测HPV类型。使用酶联免疫吸附测定（ELISA）和抑制酶免疫测定评估免疫原性。疾病结局通过组织学确诊。计算疫苗效力和95%置信区间（95%CI）。
针对HPV-16/18相关CIN2+的疫苗效力为89.8%（95%CI：39.5 - 99.5；共11例事件），针对非HPV-16/18致癌性人乳头瘤病毒相关CIN2+的效力为59.9%（95%CI：20.7 - 80.8；共39例事件），针对任何HPV类型相关CIN2+的效力为61.4%（95%CI：29.5 - 79.8；共51例事件）。该疫苗具有可接受的安全性，可诱导强烈且持久的抗体反应。
我们的研究结果证实了HPV-16/18疫苗对HPV感染及与HPV-16/18和其他致癌性HPV类型相关的宫颈疾病具有高效力和免疫原性。这些结果将作为一个基准，用于比较哥斯达黎加试验参与者正在进行的延长随访的未来研究结果。
在clinicaltrials.gov注册：NCT00128661。
