Evaluation of the effectiveness and immunogenicity of quadrivalent HPV vaccination over 10 years

Objective To assess the effectiveness and long-term immunogenicity of the quadrivalent human papillomavirus vaccine (4v HPV vaccine) in Chinese women aged 20-45 at ten years after vaccination.Methods A long-term follow-up study (LTFU) was conducted on participants from the phase Ⅲ clinical trial of the 4v HPV vaccine (NCT00834106). Questionnaires, venous blood sampling, gynecological examinations and cervical cancer screening based on liquid-based cytology were performed. Participants with cytological abnormalities and positive results in the HC2 test would be referred for colposcopy. Cervical biopsy was performed in cases where abnormalities were detected in colposcopy and HPV DNA genotyping was conducted. The vaccine effectiveness in preventing cervical precancerous lesions and cervical cancer was evaluated by comparing the differences in abnormal cytologic and pathologic results. Serum samples were collected to determine the serum HPV6, 11, 16, and 18 neutralizing antibody half inhibitory dose (50% inhibitory dose, ID50) by pseudovirus neutralization assay (PBNA). The immunogenicity of the vaccine was evaluated by calculating the positivity rate and geometric mean titer ratio (GMT ratio) of neutralizing antibody ID50.Results A total of 889 women participated in this LTFU. The number of participants of control group, vaccination group and catch-up vaccination group are 240, 453 and 196 respectively. In terms of effectiveness, no cervical lesions of any grade associated with the vaccine type were found in the vaccination group. The percentage of cytological abnormalities or pathological lesions in vaccination group was lower than those in control group (9.6% vs. 3.7%, P=0.002; 2.1% vs. 0.4%, P=0.052). In terms of immunogenicity, neutralizing antibody positivity rates of vaccine types were significantly higher in the vaccination group compared with the control group(P<0.001). The neutralizing antibody positivity rates of HPV 6, 11, 16, 18 in these two groups were 84.3% vs. 18.3%, 62.0% vs. 4.2%, 95.1% vs. 12.1% and 35.5% vs. 4.2%. The GMT ratio between the vaccination group and control groups ranged from 2.62 to 25.33, and the ratio ranged from 9.05 to 83.08 between the catch-up vaccination group and control groups.Conclusion Protective HPV vaccine-induced antibody titres can be detected up to 10 years after vaccination. Protection against cytologic abnormalities and cervical lesions associated with vaccine types was observed for at least 10 years.