BackgroundCervical 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.MethodsHealthy 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).ResultsIn 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.ConclusionsThis 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 registrationNCT00779766.
We previously reported the results of a phase II/III, double‐blind, randomized controlled study in Chinese women (NCT00779766) showing a 94.2% (95% confidence interval: 62.7–99.9) HPV‐16/18 AS04‐adjuvanted vaccine efficacy (VE) against cervical intraepithelial neoplasia grade 1 or higher (CIN1+) and/or 6‐month (M) persistent infection (PI) with a mean follow‐up of <2 years, and immunogenicity until 7 months post‐dose 1. Here, we report efficacy and safety results from an event‐triggered analysis with ~3 years longer follow‐up, and immunogenicity until M24. Healthy 18–25‐year‐old women (N = 6051) were randomized (1:1) to receive three doses of HPV‐16/18 vaccine or Al(OH)3 (control) at M0, 1, 6. VE against HPV‐16/18‐associated CIN2+, and cross‐protective VE against infections with nonvaccine oncogenic HPV types, immunogenicity, and safety were assessed. In the according‐to‐protocol efficacy cohort, in initially seronegative/DNA‐negative women (vaccine group: N = 2524; control group: N = 2535), VE against HPV‐16/18‐associated CIN2+ was 87.3% (5.3–99.7); VE against incident infection or against 6‐month persistent infection associated with HPV‐31/33/45 was 50.1% (34.3–62.3) or 52.6% (24.5–70.9), respectively. At least, 99.6% of HPV‐16/18‐vaccines remained seropositive for anti‐HPV‐16/18 antibodies; anti‐HPV‐16 and ‐18 geometric mean titers were 1271.1 EU/mL (1135.8–1422.6) and 710.0 EU/ml (628.6–801.9), respectively. Serious adverse events were infrequent (1.7% vaccine group [N = 3026]; 2.5% control group [N = 3026]). Of the 1595 reported pregnancies, nine had congenital anomalies (five live infants, three elective terminations, one stillbirth) that were unlikely vaccination‐related (blinded data). VE against HPV‐16/18‐associated CIN2+ was demonstrated and evidence of cross‐protective VE against oncogenic HPV types was shown. The vaccine was immunogenic and had an acceptable safety profile.
Objectives:Human papillomavirus is the necessary cause of cervical cancer, in particular the human papillomavirus-16/18 strains, which have been detected in ~70% of all cervical cancer cases worldwide. This study aims to assess whether other cofactors, which might be specific for the Chinese population, are involved in the development of cervical cancer. These findings may support the future direction of cervical cancer prevention.Study Design:Systematic literature review.Methods:The following databases were searched: MEDLINE, MEDLINE-IN-PROCESS, EMBASE, China National Knowledge Infrastructure, Wanfang Data and Chongqing VIP Information. The target population were adolescents or adults from mainland China. All observational studies irrespective of intervention or comparator reporting risk factors for cervical cancer were included. The Newcastle-Ottawa Scale was used to assess study quality. The impact of each outcome was reported in numerical terms.Results:A total of 2,676 articles were screened. A total of 21 articles met the inclusion criteria. All studies were case-controlled designs mostly conducted in hospitals of South-Eastern China. A total of 18 studies reported lifestyle behaviours as significant influencing factors in the development of cervical cancer. Sexual behaviour, gestational factors, screening history, disease history and socio-demographics status were reported as significant risk factors for cervical cancer development.Conclusion:This review provides an up-to-date insight of current cervical cancer risk factors in China. Due to the heterogeneity of the results, further evaluation is recommended to determine the association of these risk factors to the overall risk of cervical cancer.
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