Background:
Effective vaccination against hpv 16 and hpv 18 to prevent cervical cancer will require a high level of sustained protection against infection and precancerous lesions. our aim was to assess the long-term efficacy, immunogenicity, and safety of a bivalent hpv-16/18 l1 virus-like particle as04 vaccine against incident and persistent infection with hpv 16 and hpv 18 and their associated cytological and histological outcomes.
Methods:
We did a follow-up study of our multicentre, double-blind, randomised, placebo-controlled trial reported in 2004. we included women who originally received all three doses of bivalent hpv-16/18 virus-like particle as04 vaccine (0.5 ml; n=393) or placebo (n=383). we assessed hpv dna, using cervical samples, and did yearly cervical cytology assessments. we also studied the long-term immunogenicity and safety of the vaccine.
Findings:
More than 98% seropositivity was maintained for hpv-16/18 antibodies during the extended follow-up phase. we noted significant vaccine efficacy against hpv-16 and hpv-18 endpoints: incident infection, 96.9% (95% ci 81.3-99.9); persistent infection: 6 month definition, 94.3 (63.2-99.9); 12 month definition, 100% (33.6-100). in a combined analysis of the initial efficacy and extended follow-up studies, vaccine efficacy of 100% (42.4-100) against cervical intraepithelial neoplasia (cin) lesions associated with vaccine types. we noted broad protection against cytohistological outcomes beyond that anticipated for hpv 16/18 and protection against incident infection with hpv 45 and hpv 31. the vaccine has a good long-term safety profile.
Interpretation:
Up to 4.5 years, the hpv-16/18 l1 virus-like particle as04 vaccine is highly immunogenic and safe, and induces a high degree of protection against hpv-16/18 infection and associated cervical lesions. there is also evidence of cross protection.