Quadrivalent HPV vaccine has previously been shown to be effective, immunogenic, and safe in pre-adolescents and adolescents aged 9-15, through 8 years after vaccination. We describe final 10-year data for the long-term follow-up (LTFU) study of GARDASIL™ in this population.
In the base study of V501-Protocol 018, 1661 sexually naïve boys and girls were assigned to GARDASIL or placebo at day 1, months 2 and 6. At the end of the base study (month 30), the placebo group received GARDASIL™. Those vaccinated with GARDASIL™ in the base study are the early vaccination group (EVG). Those vaccinated with GARDASIL™ thereafter are the catch-up vaccination group (CVG). As this LTFU study does not have a placebo arm, effectiveness was estimated by calculating the incidence rate of the primary endpoints (HPV6/11/16/18 related disease or persistent infection) and comparing with rates from previous studies in young adults (aged 16-26).
A total of 1245 subjects (821 in the EVG and 424 in the CVG) had visits in the LTFU study. The median follow-up time was 9.9 years in EVG and 7.4 years in the CVG. No cases of HPV 6/11/16/18-related disease were observed. Ten subjects were detected to have persistent infection of ≥6month duration with vaccine-type HPV (females: 0.3/100 person-years at risk in the EVG and CVG, males: 0.6/100 person-years at risk in the EVG and 0.4/100 person-years at risk in the CVG). Infection persisted for ≥12 months in only 2 of these subjects. Incidence of HPV 6/11/16/18 persistent infection in female and male placebo recipients from previous studies were 6/100 person-years at risk and 4/100 person years at risk respectively. For each of HPV types 6, 11 and 16, 89%-96% remained seropositive through 10-years post-vaccination. Lower anti-HPV 18 responses were seen over time, consistent with observations in other studies of GARDASIL™ but no cases of persistent infection due to HPV type 18 were observed. No serious adverse events were reported between 8 and 10 years.
No breakthrough cases of cervical/genital disease related to HPV types 6, 11, 16, and 18 were observed among preadolescents and adolescents vaccinated with GARDASIL™ during 10 years of follow-up. Although 10 cases of persistent infection were detected, a majority (8/10) were of ˂12 months duration. Anti-HPV 6, 11, 16, and 18 antibody responses post-vaccination persisted over time. Additionally, the safety profile of GARDASIL™ during the LTFU period remained favorable.