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

Abstract

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.

Progress in Vaccination of Prophylactic Human Papillomavirus Vaccine

“…The China Food and Drug Administration approved the 2vHPV vaccine in July 2016, which was a groundbreaking decision by the Chinese authorities. Long-term follow-up of clinical studies of the efficacy of 2vHPV vaccine in Chinese women has shown that the effect of the vaccine is consistent with the results of a global study (84). The vaccine is highly immunogenic to Chinese women and does not cause serious adverse reactions.…”

<p>Identification of Potential Prognostic Long Non-Coding RNA Biomarkers for Predicting Recurrence in Patients with Cervical Cancer</p>

“…1 With the development of the prophylactic HPV vaccination and CC screening, the 5-year overall survival (OS) rate of CC has been prolonged. 2 However, in many developing countries, the 3-to 5-year OS rate of CC is less than 50%; especially in patients with advanced disease, the recurrence rate of CC is as high as 70%. 3,4 The cure rate for recurrent CC is very low, and the 5-year survival rate for relapsed patients is less than 5%.…”

Long‐term persistence of immune response to the AS04‐adjuvanted HPV‐16/18 vaccine in Chinese girls aged 9‐17 years: Results from an 8‐9‐year follow‐up phase III open‐label study

“…26,35 Although not unequivocal, the immune response elicited after natural infection with HPV can reduce the risk of reinfection with the same HPV type. 36,37 [31][32][33] The exact mechanism of protection conferred by HPV vaccination is still to be fully elucidated. Strong and persistent neutralizing antibody levels together with cellular immune response triggered by the vaccine are thought to be involved in its ability to protect the host from HPV infections, even though they may not be the only mechanism of action.…”

“…These seropositivity rates were higher compared to the persistence rates reported by Zhu and colleagues 6 years after first vaccine dose in women from the pivotal efficacy study. 32 (Table 2). These values were, respectively, 2-and 1.5-fold higher than compared to antibody GMCs measured 6 years after vaccination of women aged 18-25 years in the pivotal efficacy study 32 (presented in Table 2 for comparison).…”

“…34 Seropositivity was defined as a concentration above assay cutoff, that is, 19 ELISA Units (EU)/mL (3.1 International Units [IU]/mL) for HPV-16 and 18 EU/mL (3.2 IU/mL) for HPV-18. The conversion factors from EU to IU are 1/6.1 for HPV-16 and 1/5.7 for HPV-18.A secondary objective of the study was to compare the persistence of immune response against HPV-16/18, 8.5 years after the first vaccine dose in Chinese girls aged 9-17 years, with the antibody persistence observed 6 years after first vaccination of Chinese women aged 18-25 years from the efficacy study (NCT00779766) 32.…”