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Cited by 55Cervical Cancer and HPV ResearchWomen's cancer prevention and managementImmunotherapy and Immune Responses

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

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Zhu, Feng‐Cai, Hu, Shang‐Ying, Hong, Ying, Hu, Yue‐Mei, Zhang, Xun, Zhang, Yi‐Ju, Pan, Qin‐Jing, Zhang, Wen‐Hua +20 more·2019·Cancer Medicine
DOI 10.1002/cam4.2399PMC PMC6797633
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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.

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Authors
Zhu, F., Hu, S., Hong, Y., Hu, Y., Zhang, X., Zhang, Y., Pan, Q., Zhang, W., Zhao, F., Zhang, C., Yang, X., Yu, J., Zhu, J., Zhu, Y., Chen, F., Zhang, Q., Wang, H., Wang, C., Bi, J., Xue, S., Shen, L., Zhang, Y., He, Y., Tang, H., Karkada, N., Suryakiran, P., Bi, D., & Struyf, F.
Affiliations
  • Jiangsu Province Center for Disease Prevention and Control Nanjing China
  • National Cancer Center ‐ Cancer Hospital Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC) Beijing China
  • Nanjing Drum Tower Hospital (CN)
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
  • Lianshui Center for Disease Prevention and Control Lianshui China
  • Jintan Center for Disease Prevention and Control Jintan China
  • Xuzhou Center for Disease Prevention and Control Xuzhou China
  • Binhai Center for Disease Prevention and Control Yancheng China
  • Jiangsu Provincial Center for Disease Control and Prevention (CN)
  • GlaxoSmithKline (China) (CN)
  • GSK Shanghai China
  • GlaxoSmithKline (India) (IN)
  • GlaxoSmithKline (Belgium) (BE)
ORCID
Venue
Cancer Medicine
Publisher
Wiley
Published
2019-07-15
Volume
8
Issue
14
Pages
6195-6211
ISSN
2045-7634 (ISSN-L)
DOI
10.1002/cam4.2399
PMC
PMC6797633
OpenAlex
W2961523598
Cited by
55
References
0
Citations by year
2026: 3 · 2025: 7 · 2024: 14 · 2023: 12 · 2022: 8 · 2021: 4 · 2020: 7
FWCI
3.62
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancer Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
GlaxoSmithKline
Topics
  • Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Women's cancer prevention and management
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
AS04 adjuvant, cervical cancer prevention, cervical intraepithelial neoplasia, vaccine efficacy, immunogenicity, vaccine safety, HPV 31, HPV 33, HPV45, seroconversion, seroconversion rate, Chinese women
MeSH terms
Immunogenicity, Vaccine, Adolescent, Adult, Age Factors, China, Female, Humans, Time Factors, Vaccination, Outcome Assessment, Health Care, Papillomavirus Infections, Human papillomavirus 18, Human papillomavirus 16, Papillomavirus Vaccines, Young Adult, Public Health Surveillance

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