对来自四个北欧国家的女性进行的四价人乳头瘤病毒疫苗有效性和免疫原性的14年长期随访研究的最终分析。
Final analysis of a 14-year long-term follow-up study of the effectiveness and immunogenicity of the quadrivalent human papillomavirus vaccine in women from four nordic countries.
作者信息
Kjaer Susanne K, Nygård Mari, Sundström Karin, Dillner Joakim, Tryggvadottir Laufey, Munk Christian, Berger Sophie, Enerly Espen, Hortlund Maria, Ágústsson Ágúst Ingi, Bjelkenkrantz Kaj, Fridrich Katrin, Guðmundsdóttir Ingibjorg, Sørbye Sveinung Wergeland, Bautista Oliver, Group Thomas, Luxembourg Alain, Marshall J Brooke, Radley David, Yang Yi Shen, Badshah Cyrus, Saah Alfred
机构信息
Unit of Virus, Lifestyle & Genes, Danish Cancer Society Research Center and Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Research, Cancer Registry of Norway, Oslo, Norway.
出版信息
EClinicalMedicine. 2020 Jun 20;23:100401. doi: 10.1016/j.eclinm.2020.100401. eCollection 2020 Jun.
BACKGROUND
The quadrivalent human papillomavirus (qHPV) vaccine prevented vaccine HPV type-related infection and disease in young women in the 4-year FUTURE II efficacy study (NCT00092534). We report long-term effectiveness and immunogenicity at the end of 14 years of follow-up after enrollment in FUTURE II.
METHODS
Young women (16-23 years of age) from Denmark, Iceland, Norway, and Sweden who received three qHPV vaccine doses during the randomized, double-blind, placebo-controlled FUTURE II base study were followed for effectiveness for an additional ≥10 years through national registries. Tissue samples including but not limited to those collected during organized cervical cancer screening programs were obtained from regional biobanks to be adjudicated for histopathology diagnosis and tested for HPV DNA. The observed incidence of HPV16/18-related high-grade cervical dysplasia (primary outcome) was compared with recent historical background incidence rates in an unvaccinated population. Serum was collected at years 9 and 14 to assess antibody responses.
FINDINGS
No cases of HPV16/18-related high-grade cervical dysplasia were observed in the per-protocol effectiveness population ( = 2121; 24,099·0 person-years of follow-up) during the entire study. Vaccine effectiveness of 100% (95% CI 94·7-100) was demonstrated for ≥12 years, with a trend toward continued protection through 14 years post-vaccination. Seropositivity rates at study conclusion were >90% (HPV6/11/16) and 52% (HPV18) using competitive Luminex immunoassay, and >90% (all four HPV types) using the more sensitive IgG Luminex immunoassay.
INTERPRETATION
Vaccination of young women with qHPV vaccine offers durable protection against HPV16/18-related high-grade cervical dysplasia for ≥12 years, with a trend toward continued protection through 14 years post-vaccination, and induces sustained HPV6/11/16/18 antibody responses for up to 14 years post-vaccination. There was no evidence of waning immunity, suggesting no need for a booster dose during that period.
FUNDING
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
背景
在为期4年的FUTURE II疗效研究（NCT00092534）中，四价人乳头瘤病毒（qHPV）疫苗预防了年轻女性中与疫苗所含HPV型别相关的感染和疾病。我们报告了FUTURE II研究入组后14年随访结束时的长期有效性和免疫原性。
方法
在随机、双盲、安慰剂对照的FUTURE II基础研究中接受三剂qHPV疫苗的丹麦、冰岛、挪威和瑞典的年轻女性（16 - 23岁），通过国家登记系统额外随访≥10年以评估有效性。从区域生物样本库获取包括但不限于在有组织的宫颈癌筛查项目中收集的组织样本，进行组织病理学诊断判定并检测HPV DNA。将观察到的HPV16/18相关高级别宫颈发育异常的发病率（主要结局）与未接种人群近期的历史背景发病率进行比较。在第9年和第14年收集血清以评估抗体反应。
研究结果
在整个研究期间，符合方案的有效性人群（n = 2121；随访24,099.0人年）中未观察到HPV16/18相关高级别宫颈发育异常病例。疫苗有效性在≥12年时为100%（95%CI 94·7 - 100），接种后14年有持续保护的趋势。研究结束时，使用竞争性Luminex免疫测定法，血清阳性率>90%（HPV6/11/16）和52%（HPV18），使用更敏感的IgG Luminex免疫测定法，血清阳性率>90%（所有四种HPV型别）。
解读
用qHPV疫苗为年轻女性接种可提供针对HPV16/18相关高级别宫颈发育异常长达≥12年的持久保护，接种后14年有持续保护的趋势，并在接种后长达14年诱导持续的HPV6/11/16/18抗体反应。没有免疫减弱的证据，表明在此期间无需加强剂量。
资助
美国新泽西州肯尼沃思默克公司旗下的默克夏普&多贺美公司。
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