Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined analysis of data from the Costa Rica Vaccine and PATRICIA Trials.
Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined analysis of data from the Costa Rica Vaccine and PATRICIA Trials.
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DOI：
10.1016/s1470-2045(15)00047-9
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发表时间：
2015-07
期刊：
影响因子：
51.1
通讯作者：
Mfeeler, Cosette M.
中科院分区：
文献类型：
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作者：
Kreimer, Aimee R.;Struyf, Frank;Del Rosario-Raymundo, Mora Rowena;Hildeshim, Allan;Skinner, S. Rachel;Wacholder, Sholom;Garland, Suzanne M.;Herrero, Rolando;David, Marfe-Pierre;Mfeeler, Cosette M.
有限的数据表明，一剂或两剂HPV疫苗可提供与三剂方案相似的保护。本研究旨在进一步评估HPV-16/18疫苗剂量减少的有效性问题。来自哥斯达黎加疫苗试验的汇总水平数据（CVT; NCT 00128661）和年轻人中的乳头瘤试验（帕特丽夏; NCT 001226810），在年轻女性中进行的HPV-16/18 AS 04佐剂疫苗的两项III期对照、随机、双盲临床试验，在一项事后分析（GSK e-track 202142）中合并，以研究4年随访后较少剂量HPV-16/18疫苗的有效性。妇女被随机分配接受三剂HPV-16/18疫苗或对照疫苗;但有些人接受的剂量较少。在排除了随访时间<12个月的女性或入组时HPV 16/18 DNA阳性的女性（对于HPV 16/18终点）后，根据三次（n= 11，110 HPV：11，217对照），两次（n=611：574）和一次（N=292：251）剂量后一次性检测到的HPV感染计算疫苗有效性（VE）。该研究的主要目的是确定完整和初治队列中的HPV 16/18 VE，并通过接受的剂量数探索对非疫苗HPV类型的保护。三剂VE预防HPV 16/18感染的发生率为77.0%（95%CI 74.7 ~ 79.1%），两剂为76.0%（95%CI 62.0 ~ 85.3%），一剂为85.7%（95%CI 70.7 ~ 93.7%）。三剂VE对HPV 31/33/45感染的预防率为59.7%（95%CI 56.0至63.0%），两剂为37.7%（95%CI 12.4至55.9%），一剂为36.6%（95%CI − 5.4至62.2%）。然而，在六个月时接受第二剂疫苗的两剂女性（而不是在一个月时接受第二剂疫苗的女性）对HPV 31/33/45的疗效估计与三剂组相似（VE 68·1%，95%CI 27·0至87·0%;仅限CVT数据）。在15至25岁的女性接种疫苗后四年，一剂和两剂HPV 16/18疫苗似乎可以预防宫颈HPV 16/18感染，与三剂疫苗方案提供的保护相似。间隔6个月的两次给药还提供了有限的交叉保护。这些数据支持直接评价HPV 16/18疫苗的单剂量有效性。CVT试验由美国国家癌症研究所NCI（合同N 01-CP-11005）赞助和资助，由美国国立卫生研究院妇女健康研究办公室提供资金支持，并在哥斯达黎加卫生部的支持下完成。根据与NCI的临床试验协议，由GlaxoSmithKline Biologicals SA提供CVT疫苗。GlaxoSmithKline Biologicals SA根据美国食品药品监督管理局BB-IND 7920为与公司监管提交需求相关的试验方面提供支持。PATRICIA试验由GlaxoSmithKline Biologicals SA申办。
Limited data suggest one or two doses of the HPV vaccines confer similar protection to the three-dose regimen. This study aimed to further evaluate the question of reduced-dose efficacy of the HPV-16/18 vaccine. Summary-level data from the Costa Rica Vaccine Trial (CVT; NCT00128661) and the PApilloma TRIal against Cancer In young Adults (PATRICIA; NCT001226810), two phase III controlled, randomized, double-blind, clinical trials of the HPV-16/18 AS04-adjuvanted vaccine among young women, were combined in a post-hoc analysis (GSK e-track 202142) to investigate efficacy of fewer doses of the HPV-16/18 vaccine after four years of follow-up. Women were randomly assigned to receive three doses of the HPV-16/18 vaccine or to a control vaccine; yet some received fewer doses. After excluding women with <12-months follow-up or those HPV16/18 DNA-positive at enrollment (for the HPV16/18 endpoint), vaccine efficacy (VE) was calculated against one-time detection of incident HPV infections after three (n=11,110 HPV:11,217control), two (n=611:574), and one (N=292:251) dose(s). The main aim of the study was to ascertain HPV16/18 VE in both full and naïve cohorts, as well as to explore protection conferred against non-vaccine HPV types, by number of doses received. VE against incident HPV16/18 infections for three doses was 77·0% (95%CI 74·7 to 79·1%), two doses was 76·0% (95%CI 62·0 to 85·3%), and one dose was 85·7% (95%CI 70·7 to 93·7%). VE against incident HPV31/33/45 infections for three doses was 59·7% (95%CI 56·0 to 63·0%), two doses was 37·7% (95%CI 12·4 to 55·9%), and one dose was 36·6% (95%CI −5·4 to 62·2%). However, two-dose women who received their second dose at six months, but not those receiving it at one month, had efficacy estimates against HPV 31/33/45 similar to the three-dose group (VE 68·1%, 95%CI 27·0 to 87·0%; CVT data only). Four years following vaccination of women aged 15 to 25 years, one and two dose(s) of the HPV16/18 vaccine appear to protect against cervical HPV16/18 infections, similar to the protection provided by the three-dose schedule. Two doses separated by six months additionally provided limited cross-protection. These data argue for a direct evaluation of one-dose efficacy of the HPV16/18 vaccine. The CVT trial was sponsored and funded by the US National Cancer Institute, NCI (contract N01-CP-11005), with funding support from the National Institutes of Health Office of Research on Women’s Health, and done with the support from the Ministry of Health of Costa Rica. Vaccine was provided for CVT by GlaxoSmithKline Biologicals SA, under a Clinical Trials Agreement with the NCI. GlaxoSmithKline Biologicals SA provided support for aspects of the trial associated with regulatory submission needs of the company under US Food and Drug Administration BB-IND 7920. The PATRICIA trial was sponsored by GlaxoSmithKline Biologicals SA.