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. Issue 27 (12th June 2019)

• Record Type: Journal Article
• Authors: Wei, Lihui; Xie, Xing; Liu, Jihong; Zhao, Yun; Chen, Wen; Zhao, Chao; Wang, Shaoming; Liao, Xueyan; Shou, Qiong; Qiu, Yuanzheng; Qiao, Youlin; Saah, Alfred J.
• Is Part Of: Vaccine. Volume 37:Issue 27(2019)
• Page Start: 3617
• Page End: 3624
• Publication Date: 2019-06-12
• Subjects: Efficacy -- Genital diseases -- Persistent infection -- Quadrivalent human papillomavirus vaccine -- Randomized controlled trial; 6-M PI 6-month persistent infection -- 12-M PI 12-month persistent infection -- AIS adenocarcinoma in situ -- ASC-H atypical squamous cells-cannot exclude HSIL -- CI confidence interval -- CIN cervical intraepithelial neoplasia -- cLIA competitive Luminex immunoassay -- EEC endo/ecto-cervical -- EGL external genital lesion -- FAS full analysis set -- GW genital warts -- HNRT naïve to relevant HPV type -- HPV human papillomavirus -- HSIL high-grade squamous intraepithelial lesion -- IPP Independent Pathology Panel -- LEEP loop electrosurgical excision procedure -- LVPP labial/vulvar/perineal/perianal -- mMU milli-Merck unit -- Pap Papanicolaou -- PCR polymerase chain reaction -- PI persistent infection -- PPE per-protocol efficacy -- qHPV quadrivalent human papillomavirus -- VaIN vaginal intraepithelial neoplasia -- VIN vulvar intraepithelial neoplasia; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2018.08.009
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: A quadrivalent HPV (qHPV) vaccine was assessed in a randomized, controlled trial. Vaccine efficacy was assessed up to 78 months in Chinese women 20–45 years of age. 100% efficacy against HPV16/18-related high-grade cervical precancerous lesion. 100% efficacy against HPV6/11/16/18-related any-grade cervical precancerous lesion. 97.5% efficacy against HPV6/11/16/18-related cervical 12-month persistent infection. 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.