Department of Obstetrics and Gynecology, Jichi Medical University, Saitama Medical Center, Saitama, Japan.
Int J Gynecol Cancer. 2010 Jul;20(5):847-55. doi: 10.1111/IGC.0b013e3181da2128.
Human papillomavirus (HPV) type 16/18 AS04-adjuvanted vaccine was shown to be highly immunogenic and generally well tolerated in the interim analysis of a phase 2 double-blind, randomized controlled multicenter study in Japanese healthy women aged 20 to 25 years. Vaccine efficacy, immunogenicity, and safety are assessed in this study through 24 months after the first vaccination.
Japanese women aged 20 to 25 years were randomly assigned to receive either HPV-16/18 AS04-adjuvanted vaccine (n = 519) or hepatitis A vaccine (n = 521) at 0, 1, and 6 months. Women were assessed for virological, cytological, and histological end points associated with HPV-16/18 and 12 other oncogenic HPV types (types 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) in cervical specimens and for the vaccine safety and immunogenicity. Antibody concentrations were measured by an enzyme-linked immunosorbent assay. Primary efficacy analysis was performed in the according-to-protocol cohort for efficacy, primary immunogenicity analysis was performed in the according-to-protocol cohort for immunogenicity, and primary safety analysis was done in the total vaccinated cohort.
Vaccine efficacy against persistent infections (6 month definition) associated with HPV-16/18 was 100% (95.5% confidence interval, 71.3-100; P < 0.0001). Vaccine efficacy against cervical intraepithelial neoplasia 1+ associated with 14 oncogenic HPV types was 64.9% (95.5% confidence interval, 4.9-89.0; P = 0.02). At 24 months after the first dose of the vaccine, geometric mean antibody titers against HPV-16 and HPV-18 were 1521.5 enzyme-linked immunosorbent assay U/mL and 627.4 enzyme-linked immunosorbent assay U/mL, respectively. The HPV-16/18 AS04-adjuvanted vaccine had a clinically acceptable safety profile.
The HPV-16/18 AS04-adjuvanted vaccine showed excellent prophylactic efficacy against 6-month persistent infection with HPV-16/18. The HPV-16/18 AS04-adjuvanted vaccine was generally well tolerated and immunogenic in the study population of healthy Japanese women aged 20 to 25 years.
在一项针对 20 至 25 岁日本健康女性的 2 期双盲、随机对照多中心研究的中期分析中，人乳头瘤病毒（HPV）16/18 AS04 佐剂疫苗显示出高度的免疫原性和总体良好的耐受性。本研究通过接种第一针后 24 个月评估疫苗的有效性、免疫原性和安全性。
20 至 25 岁的日本女性被随机分配至接受 HPV-16/18 AS04 佐剂疫苗（n=519）或甲型肝炎疫苗（n=521），于 0、1 和 6 个月接种。通过对宫颈标本中 HPV-16/18 和其他 12 种致癌 HPV 型（HPV 31、33、35、39、45、51、52、56、58、59、66 和 68）相关的病毒学、细胞学和组织学终点来评估疫苗的安全性和免疫原性。通过酶联免疫吸附试验（ELISA）测量抗体浓度。根据方案对有效性进行主要分析，根据方案对免疫原性进行主要分析，对总接种人群进行主要安全性分析。
HPV-16/18 持续性感染（6 个月定义）的疫苗效力为 100%（95.5%置信区间，71.3-100；P<0.0001）。针对与 14 种致癌 HPV 型相关的宫颈上皮内瘤变 1+的疫苗效力为 64.9%（95.5%置信区间，4.9-89.0；P=0.02）。接种疫苗第一针后 24 个月，针对 HPV-16 和 HPV-18 的几何平均抗体滴度分别为 1521.5 ELISA U/mL 和 627.4 ELISA U/mL。HPV-16/18 AS04 佐剂疫苗具有可接受的临床安全性。
HPV-16/18 AS04 佐剂疫苗对 HPV-16/18 的 6 个月持续性感染显示出优异的预防性疗效。在 20 至 25 岁的日本健康女性研究人群中，HPV-16/18 AS04 佐剂疫苗总体耐受性良好且具有免疫原性。
