Efficacy, immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Chinese women aged 18-25 years: results from a randomized controlled trial

Abstract

This phase II/III, double-blind, randomized trial assessed the efficacy, immunogenicity and safety of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in young Chinese women (ClinicalTrials.gov registration NCT00779766). Women aged 18-25 years from Jiangsu province were randomized (1:1) to receive HPV vaccine (n = 3,026) or Al(OH)3 control (n = 3,025) at months 0, 1 and 6. The primary objective was vaccine efficacy (VE) against HPV-16/18 associated 6-month persistent infection (PI) and/or cervical intraepithelial neoplasia (CIN) 1+. Secondary objectives were VE against virological and clinical endpoints associated with HPV-16/18 and with high-risk HPV types, immunogenicity and safety. Mean follow-up for the according-to-protocol cohort for efficacy (ATP-E) was ∼15 months after the third dose. In the ATP-E (vaccine = 2,889; control = 2,894), for initially HPV DNA negative and seronegative subjects, HPV-16/18 related VE (95% CI) was 94.2% (62.7, 99.9) against 6-month PI and/or CIN1+ and 93.8% (60.2, 99.9) against cytological abnormalities. VE against HPV-16/18 associated CIN1+ and CIN2+ was 100% (-50.4, 100) and 100% (-140.2, 100), respectively (no cases in the vaccine group and 4 CIN1+ and 3 CIN2+ cases in the control group). At Month 7, at least 99.7% of initially seronegative vaccine recipients had seroconverted for HPV-16/18; geometric mean antibody titres (95% CI) were 6,996 (6,212 to 7,880) EU/mL for anti-HPV-16 and 3,309 (2,942 to 3,723) EU/mL for anti-HPV-18. Safety outcomes between groups were generally similar. The HPV-16/18 AS04-adjuvanted vaccine is effective, immunogenic and has a clinically acceptable safety profile in young Chinese women. Prophylactic HPV vaccination has the potential to substantially reduce the burden of cervical cancer in China.

Keywords: China; efficacy; human papillomavirus vaccine; immunogenicity; safety.

Figure 1

Flow of participants through the trial. TVC, total vaccinated cohort (all vaccinated subjects for whom data were available); TVC-E, total vaccinated cohort for efficacy (all vaccinated women for whom efficacy data were available and who had normal or low-grade cytology at baseline); ATP-E, according to protocol cohort for efficacy (all evaluable women who met eligibility criteria and complied with protocol procedures who received three doses of vaccine or control and had normal or low-grade cytology at baseline). *n*: number present in one group only and duplicated to avoid unblinding of ongoing study. ¹Completion status at Month 24 was unknown for these subjects at the time of this event-triggered analysis. ²ASC-H, HSIL, AGC or malignancy. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 2

GMTs at Month 0 and Month 7 for women in the vaccine group by baseline serostatus (according-to-protocol cohort for immunogenicity). CI: confidence interval; GMT: geometric mean antibody titre; S-: seronegative prior to vaccination (n = 244 for anti-HPV-16 and n = 289 for anti-HPV-18); S+, seropositive (titre ≥8 EU/mL for anti-HPV-16 and ≥7 EU/mL for anti-HPV-18) prior to vaccination (n = 107 for anti-HPV-16 and n = 62 for anti-HPV-18); Total, all women irrespective of serostatus (n = 351). Natural infection, GMT in women who had cleared a natural infection. Plateau level, GMT at the plateau level (Month 45–50) in a previous study in women aged 15–25 years in which sustained protection with the HPV-16/18 AS04-adjuvanted vaccine was shown up to 6.4 years after first vaccination. Numbers at the base of each bar are the percentage of seropositive women. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]