Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial
Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial
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DOI：
10.1016/s1470-2045(11)70287-x
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发表时间：
2012-01-01
期刊：
影响因子：
51.1
通讯作者：
Lehtinen, Matti
中科院分区：
文献类型：
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作者：
Wheeler, Cosette M.;Castellsague, Xavier;Lehtinen, Matti
背景我们在PATRICIA随访4年后的研究结束分析中评价了人乳头瘤病毒HPV-16/18 AS 04佐剂疫苗对非疫苗致癌HPV类型的有效性。方法年龄在15-25岁的健康女性，一生中的性伴侣不超过6个，被包括在PATRICIA中，不管她们的基线HPV DNA状态如何，HPV-16或HPV-18血清状态或细胞学。通过基于互联网的中央随机化系统，使用最小化算法将女性随机分配（1：1）接种HPV-16/18疫苗或对照甲型肝炎疫苗，以考虑年龄范围和研究中心。该研究是双盲的。PATRICIA的主要终点之前已有报告;本分析在研究结束分析中评价了疫苗对非疫苗致癌HPV类型的交叉保护性有效性。对三个队列进行了分析：疗效符合方案队列（ATP-E;疫苗n=8067，对照n=8047），总接种HPV初治队列（TVC初治;基线时无14种致癌HPV类型感染的证据，近似于首次性行为前的年轻青少年;疫苗组n=5824，对照组n=5820），（TVC;所有接受至少一剂疫苗的女性，接近包括性活跃女性的追赶人群;疫苗n=9319，对照=9325）。针对6个月持续感染、与12种非疫苗HPV类型相关的2级或更高级别宫颈上皮内瘤变（CIN 2+）（单独或作为复合终点）以及与12种非疫苗HPV类型复合相关的CIN 3+，评价了疫苗有效性。该研究在ClinicalTrials.gov注册，编号NCT 00122681。结果在HPV-33、HPV-31、HPV-45和HPV-51的队列中观察到针对持续感染和CIN 2+（伴或不伴HPV-16/18共感染）的一致疫苗有效性。在针对CIN 2+的疫苗有效性的最保守分析中，其中删除了所有HPV-16/18共感染病例，在所有队列中观察到HPV-33的疫苗有效性，在ATP-E和TVC初治组中观察到HPV-31的疫苗有效性。与12种非疫苗HPV类型的复合物相关的针对CIN 2+的疫苗效力（31、33、35、39、45、51、52、56、58、59、66和68），有或无HPV-16/18共感染，为46.8% ATP-E组为56.2%（37.2-69.9），TVC组为34.2%（20.4-45.8）。CIN 3+的相应值为73.8%，（48.3-87.9），91.4%（65.0-99.0）和47.5%（22.8-64.8）.来自PATRICIA研究结束分析的解释数据显示HPV-16/18疫苗对四种致癌非疫苗HPV类型-HPV-33、HPV-31、HPV-45、和HPV-51-在代表不同妇女群体的不同试验队列中。
Background We evaluated the efficacy of the human papillomavirus HPV-16/18 AS04-adjuvanted vaccine against non-vaccine oncogenic HPV types in the end-of-study analysis after 4 years of follow-up in PATRICIA (PApilloma TRIal against Cancer In young Adults).Methods Healthy women aged 15-25 years with no more than six lifetime sexual partners were included in PATRICIA irrespective of their baseline HPV DNA status, HPV-16 or HPV-18 serostatus, or cytology. Women were randomly assigned (1:1) to HPV-16/18 vaccine or a control hepatitis A vaccine, via an internet-based central randomisation system using a minimisation algorithm to account for age ranges and study sites. The study was double-blind. The primary endpoint of PATRICIA has been reported previously; the present analysis evaluates cross-protective vaccine efficacy against non-vaccine oncogenic HPV types in the end-of-study analysis. Analyses were done for three cohorts: the according-to-protocol cohort for efficacy (ATP-E; vaccine n=8067, control n=8047), total vaccinated HPV-naive cohort (TVC-naive; no evidence of infection with 14 oncogenic HPV types at baseline, approximating young adolescents before sexual debut; vaccine n=5824, control n=5820), and the total vaccinated cohort (TVC; all women who received at least one vaccine dose, approximating catch-up populations that include sexually active women; vaccine n=9319, control=9325). Vaccine efficacy was evaluated against 6-month persistent infection, cervical intraepithelial neoplasia grade 2 or greater (CIN2+) associated with 12 non-vaccine HPV types (individually or as composite endpoints), and CIN3+ associated with the composite of 12 non-vaccine HPV types. This study is registered with ClinicalTrials.gov, number NCT00122681.Findings Consistent vaccine efficacy against persistent infection and CIN2+ (with or without HPV-16/18 co-infection) was seen across cohorts for HPV-33, HPV-31, HPV-45, and HPV-51. In the most conservative analysis of vaccine efficacy against CIN2+, where all cases co-infected with HPV-16/18 were removed, vaccine efficacy was noted for HPV-33 in all cohorts, and for HPV-31 in the ATP-E and TVC-naive. Vaccine efficacy against CIN2+ associated with the composite of 12 non-vaccine HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68), with or without HPV-16/18 co-infection, was 46.8% (95% CI 30.7-59.4) in the ATP-E, 56.2% (37.2-69.9) in the TVC-naive, and 34.2% (20.4-45.8) in the TVC. Corresponding values for CIN3+ were 73.8% (48.3-87.9), 91.4% (65.0-99.0), and 47.5% (22.8-64.8).Interpretation Data from the end-of-study analysis of PATRICIA show cross-protective efficacy of the HPV-16/18 vaccine against four oncogenic non-vaccine HPV types-HPV-33, HPV-31, HPV-45, and HPV-51-in different trial cohorts representing diverse groups of women.