Lihui Wei1, Xing Xie2, Jihong Liu3, Yun Zhao1, Wen Chen4, Chao Zhao1, Shaoming Wang4, Xueyan Liao5, Qiong Shou5, Yuanzheng Qiu5, Youlin Qiao6, Alfred J Saah7. 1. Department of Obstetrics and Gynecology, Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China. 2. Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Hangzhou 310006, China. 3. Department of Gynecologic Oncology, Cancer Center, Sun Yat-sen University, 651 Dongfeng Road East, Guangzhou 510060, China. 4. Department of Cancer Epidemiology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 South Panjiayuan Lane, Beijing 100021, China. 5. MSD R&D (China), 21 Rongda Road, Wangjing R&D Base, Zhongguancun Electronic Zone West Zone, Chaoyang District, Beijing 100012, China. 6. Department of Cancer Epidemiology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 South Panjiayuan Lane, Beijing 100021, China. Electronic address: qiaoy@cicams.ac.cn. 7. Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA. Electronic address: Alfred_saah@merck.com.
Abstract
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.
RCT Entities:
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.
Authors: Andreas Ährlund-Richter; Liqin Cheng; Yue O O Hu; Mikaela Svensson; Alexandra A L Pennhag; Ramona G Ursu; Linnea Haeggblom; Nathalie Grün; Torbjörn Ramqvist; Lars Engstrand; Tina Dalianis; Juan Du Journal: Front Cell Infect Microbiol Date: 2019-03-20 Impact factor: 5.293