四价人乳头瘤病毒疫苗在中国女性人群中针对持续性感染和生殖器疾病的效力：一项随机、安慰剂对照、随访 78 个月的临床试验。
Efficacy of quadrivalent human papillomavirus vaccine against persistent infection and genital disease in Chinese women: A randomized, placebo-controlled trial with 78-month follow-up.
机构信息
Department of Obstetrics and Gynecology, Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China.
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Hangzhou 310006, China.
出版信息
Vaccine. 2019 Jun 12;37(27):3617-3624. doi: 10.1016/j.vaccine.2018.08.009. Epub 2018 Aug 16.
BACKGROUND
A quadrivalent human papillomavirus vaccine (qHPV; HPV6/11/16/18) has demonstrated efficacy and effectiveness worldwide. We report qHPV vaccine efficacy for up to 6.5 years after first administration among Chinese women 20-45 years of age.
METHODS
In this randomized, double-blind, placebo-controlled, multicenter, Phase 3 study (NCT00834106), women were randomized 1:1 to receive 3 doses of qHPV vaccine or placebo (Day 1, Month 2, Month 6). Endo-ecto-cervical and external genital swabs were collected for HPV testing and gynecologic examinations, and cervical cytology testing were performed at Day 1 and Months 7, 12, 18, 24, 30, 42, 54, 66, and 78. Any abnormality in cytology testing would trigger colposcopy examination and cervical biopsy, if necessary. Efficacy against genital disease, persistent infection, and the composite endpoint was assessed. Primary efficacy analyses were conducted in the per-protocol efficacy (PPE) population.
RESULTS
Of 3006 participants randomized, 2759 (91.8%) and 2374 (79%) completed the Month 30 and Month 78 visits, respectively. At Month 78, efficacy among women aged 20-45 years was 100% (95% CI: 32.3, 100; 0 vs 7 cases) and 100% (95% CI: 70.9, 100; 0 vs 14 cases) against HPV16/18-related cervical intraepithelial neoplasia Grade 2 or 3, adenocarcinoma in situ, and cervical cancer (CIN 2+) and HPV6/11/16/18-related CIN 1+, respectively, in the PPE population. The efficacy against cervical 6-month and 12-month persistent infection was 91.6% (95% CI: 66.0, 99.0) and 97.5% (95% CI: 85.1, 99.9) at Month 30 and Month 78, respectively, in the PPE population. The vaccine also reduced the rate of cervical cytology abnormalities associated with HPV6/11/16/18, with an efficacy of 94.0% (95% CI: 81.5, 98.8). The vaccine was generally well tolerated (reported separately).
CONCLUSION
The qHPV vaccine is efficacious against endpoints of persistent infection and genital precancerous lesions in Chinese women aged 20-45 years.
背景
四价人乳头瘤病毒疫苗（qHPV；HPV6/11/16/18）在全球范围内已被证明具有疗效和效果。我们报告了在中国 20-45 岁女性中首次接种 qHPV 疫苗后长达 6.5 年的疫苗有效性。
方法
在这项随机、双盲、安慰剂对照、多中心、3 期研究（NCT00834106）中，女性按 1:1 随机分配接受 3 剂 qHPV 疫苗或安慰剂（第 1 天、第 2 个月、第 6 个月）。进行阴道-外阴-宫颈和外阴生殖器拭子采集，用于 HPV 检测和妇科检查，并在第 1 天和第 7、12、18、24、30、42、54、66 和 78 个月进行宫颈细胞学检测。如果细胞学检测出现任何异常，将触发阴道镜检查和宫颈活检。
疗效评估包括生殖器疾病、持续性感染和复合终点。主要疗效分析在符合方案疗效（PPE）人群中进行。
结果
在 3006 名随机分配的参与者中，分别有 2759 名（91.8%）和 2374 名（79%）完成了第 30 个月和第 78 个月的访视。在第 78 个月，20-45 岁女性的疗效为 100%（95%CI：32.3，100；0 例与 7 例）和 100%（95%CI：70.9，100；0 例与 14 例），针对 HPV16/18 相关的宫颈上皮内瘤变 2 级或 3 级、原位腺癌和宫颈癌（CIN2+）以及 HPV6/11/16/18 相关的 CIN1+，分别在 PPE 人群中。在 PPE 人群中，疫苗对宫颈 6 个月和 12 个月持续性感染的疗效分别为 91.6%（95%CI：66.0，99.0）和 97.5%（95%CI：85.1，99.9）。疫苗还降低了与 HPV6/11/16/18 相关的宫颈细胞学异常的发生率，其疗效为 94.0%（95%CI：81.5，98.8）。疫苗的总体耐受性良好（另文报告）。
结论
qHPV 疫苗对中国 20-45 岁女性的持续性感染和生殖器癌前病变终点具有疗效。
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