Human papillomavirus (HPV) causes up to 5% of male and 10% female cancers. Prophylactic HPV vaccines are efficacious against precancerous cervical lesions but the impact of different vaccination strategies is unknown. Results of a community-randomized, controlled, partially blind phase (III)/IV study (HPV-040: NCT 00534638) on the co-primary end-point: overall effectiveness (comprising direct vaccine efficacy (VE) and indirect effectiveness) of gender-neutral and girls-only vaccination, and direct VE of HPV-16/18 AS04-adjuvanted vaccine are reported.
In 2007-10, 80.272 adolescents born 1992-5 from 33 randomized urban/semi-urban communities in Finland, a priori stratified into 12 low, 9 intermediate and 12 high HPV-16/18 seroprevalence were invited (1). In 11 Arm A communities 90% of vaccinated girls and boys received HPV-16/18 AS04-adjuvanted vaccine, in 11 Arm B communities 90% of vaccinated girls received the HPV-16/18 vaccine and all vaccinated boys received hepatitis B-virus (HBV) vaccine. In 11 Arm C communities all vaccinees received HBV-vaccine. HPV DNA prevalence in altogether 10.826 cervical and 4.871 oropharyngeal samples of HPV-16/18 vaccinated and non-HPV-16/18 vaccinated 18.5 year-old girls were determined by SPF10 and/or MALTI-DOF PCRs.
Enrolment of 32.175 adolescents during immunization phase: 20.513 girls (51-53% participation rate) and 11.662 boys (22-32% participation rate) was uniform by birth cohort (1). The mobility among different communities between 15 and 18.5 years was low and comparable between arms. Smoking/alcohol consumption and sexual health characteristics were generally comparable in the different arms. Baseline HPV prevalence between arms was disproportionate, and there were no statistically significant differences between the overall effectiveness estimates of the HPV-16/18 vaccination strategies. The overall effectiveness of HPV-16/18 vaccination in all 18.5 year-old females for gender-neutral and girls-only vaccination strategies was respectively 24% (95%CI -19-51) and 50% (95%CI 20-68) based on stratified, cluster-adjusted Mantel-Haenszel test, and 36% (95%CI 6-56) and 51% (95%CI 33-64) based on multivariate logistic regression adjusted for covariates. Direct VE against HPV-16/18 infection as measured by prevalence in the HPV-16/18 vaccinated 18.5 year-old females from the combined A and B vs. C arms was high against both HPV-16/18 genital infection (adj. VE 93.3%, 95%CI 87.7-96.4), and against oropharyngeal infection (adj. VE 82%, 95%CI 47-94).
Randomized trial-based data on the impact of different HPV vaccination strategies on HPV prevalence will hopefully soon guide implementation of vaccination programs.
Funding GlaxoSmithKline Biological SA
1. Lehtinen M, et al. Vaccine 33:1284-1290, 2015