Human Papillomavirus (HPV) infection causes significant disease burden in China. Here we report a randomized, double-blind, placebo-controlled multicenter trial conducted in Chinese healthy women to assess the safety and efficacy of a quadrivalent HPV (types 6, 11, 16, 18) L1 virus-like–particle vaccine (Gardasil®) against persistent infection and genital diseases.
3006 participants aged 20 to 45 years were enrolled and randomized (1:1) to receive HPV vaccine or placebo at Day 1, Month 2 and 6. The efficacy was followed up till Month 78. The primary efficacy endpoint was HPV 16/18-related cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3), adenocarcinoma in situ (AIS) or cervical cancer. Other efficacy endpoints included HPV 6/11/16/18-related: 1) CIN of any grade, AIS or cervical cancer (CIN plus); 2) 12-month persistent infection (PI); 3) 12-month PI, CIN plus or external genital lesions (EGLs, including genital warts, vulvar or vaginal intraepithelial neoplasia, vulvar or vaginal cancer); 4) EGLs. The efficacy analyses were done on the type-specific per-protocol efficacy (PPE) population who received all the 3 doses and were naïve to the relevant HPV types through 1 month after the third dose. Injection-site and systemic adverse events (AEs) were recorded within 15 days after each dosing. Serious AEs (SAEs) in the participants and their infants/fetuses, and pregnancy outcomes were collected throughout the study. (ClinicalTrials.gov registry: NCT00834106)
0 and 7 cases of HPV 16/18-related CIN2/3, AIS or cervical cancer were observed among 1,265 and 1,237 participants in the vaccine and placebo groups, respectively, translating into an efficacy of 100% (95%CI: 32.3, 100). The efficacies against HPV 6/11/16/18-related genital diseases or infection were: 1) 100% (95%CI: 70.9, 100) for CIN plus; 2) 91.0% (95%CI: 77.7, 97.2) for 12-month PI; 3) 91.8% (95%CI: 79.8, 97.4) for 12-month PI, CIN plus or EGLs. No EGLs case was observed. 926 (61.8%) and 856 (57.1%) participants reported AEs in the vaccine and placebo groups, respectively. Injection-site AEs were more frequent in the vaccine group (37.6% vs. 27.8%, p<0.001). Systemic AEs incidences were similar (51.4% vs. 50.1%). 38 (2.5%) and 43 (2.9%) participants reported SAEs in the vaccine and placebo groups, respectively. Incidences of congenital anomaly in infants and aborted fetuses were 2.3% (11/488) in vaccine group and 1.4% (6/444) in placebo group ( p=0.3371).
The quadrivalent HPV vaccine demonstrated good safety profile and high efficacy against persistent infection, any-grade and high-grade cervical precancerous lesions in Chinese healthy adult women.