Cancer Medicine (Oct 2019)

Efficacy, immunogenicity and safety of the AS04‐HPV‐16/18 vaccine in Chinese women aged 18‐25 years: End‐of‐study results from a phase II/III, randomised, controlled trial

  • Feng‐Cai Zhu,
  • Shang‐Ying Hu,
  • Ying Hong,
  • Yue‐Mei Hu,
  • Xun Zhang,
  • Yi‐Ju Zhang,
  • Qin‐Jing Pan,
  • Wen‐Hua Zhang,
  • Fang‐Hui Zhao,
  • Cheng‐Fu Zhang,
  • Xiaoping Yang,
  • Jia‐Xi Yu,
  • Jiahong Zhu,
  • Yejiang Zhu,
  • Feng Chen,
  • Qian Zhang,
  • Hong Wang,
  • Changrong Wang,
  • Jun Bi,
  • Shiyin Xue,
  • Lingling Shen,
  • Yan‐Shu Zhang,
  • Yunkun He,
  • Haiwen Tang,
  • Naveen Karkada,
  • Pemmaraju Suryakiran,
  • Dan Bi,
  • Frank Struyf

DOI
https://doi.org/10.1002/cam4.2399
Journal volume & issue
Vol. 8, no. 14
pp. 6195 – 6211

Abstract

Read online

Abstract Background Cervical cancer is a major public health concern in China. We report the end‐of‐study results of a phase II/III trial to assess the efficacy, immunogenicity, and safety of the AS04‐human papillomavirus (HPV)‐16/18 vaccine in Chinese women aged 18‐25 years followed for up to 72 months after first vaccination. Results of approximately 57 months following first vaccination have been previously reported. Methods Healthy 18‐25‐year‐old women (N = 6051) were randomized (1:1) to receive three doses of AS04‐HPV‐16/18 vaccine or Al(OH)3 (control) at Months 0‐1‐6. Vaccine efficacy against HPV‐16/18 infection and cervical intraepithelial neoplasia (CIN), cross‐protective vaccine efficacy against infections and lesions associated with nonvaccine oncogenic HPV types, immunogenicity, and safety were assessed. Efficacy was assessed in the according‐to‐protocol efficacy (ATP‐E) cohort (vaccine N = 2888; control N = 2892), total vaccinated cohort for efficacy (TVC‐E; vaccine N = 2987; control N = 2985) and TVC‐naïve (vaccine N = 1660; control N = 1587). Results In initially HPV‐16/18 seronegative/DNA‐negative women, vaccine efficacy against HPV‐16/18‐associated CIN grade 2 or worse was 87.3% (95% CI: 5.5, 99.7) in the ATP‐E, 88.7% (95% CI: 18.5, 99.7) in the TVC‐E, and 100% (95% CI: 17.9, 100) in the TVC‐naïve. Cross‐protective efficacy against incident infection with HPV‐31, HPV‐33 and HPV‐45 was 59.6% (95% CI: 39.4, 73.5), 42.7% (95% CI: 15.6, 61.6), and 54.8% (95% CI: 19.3, 75.6), respectively (ATP‐E). At Month 72, >95% of initially seronegative women who received HPV vaccine in the ATP cohort for immunogenicity (N = 664) remained seropositive for anti‐HPV‐16/18 antibodies; anti‐HPV‐16 and anti‐HPV‐18 geometric mean titers were 678.1 EU/mL (95% CI: 552.9, 831.5) and 343.7 EU/mL (95% CI: 291.9, 404.8), respectively. Serious adverse events were infrequent (1.9% vaccine group [N = 3026]; 2.7% control group [N = 3025]). Three and zero women died in the control group and the vaccine group respectively. New onset autoimmune disease was reported in two women in the vaccine group and two in the control group. Conclusions This is the first large‐scale randomized clinical trial of HPV vaccination in China. High and sustained vaccine efficacy against HPV‐16/18‐associated infection and cervical lesions was demonstrated up to Month 72. The vaccine had an acceptable safety profile. Combined with screening, prophylactic HPV vaccination could potentially reduce the high burden of HPV infection and cervical cancer in China. Trial registration NCT00779766.

Keywords