End-of-study safety, immunogenicity, and efficacy of quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine in adult women 24–45 years of age

Abstract

Background:Previous analyses from a randomised trial in women aged 24–45 years have shown the quadrivalent human papillomavirus (qHPV) vaccine to be efficacious in the prevention of infection, cervical intraepithelial neoplasia (CIN), and external genital lesions (EGLs) related to HPV 6/11/16/18. In this report, we present end-of-study efficacy, safety, and immunogenicity data with a median follow-up time of 4.0 years.Methods:We enrolled 3819 24–45-year-old women with no history of cervical disease or genital warts in the past 5 years. Women received quadrivalent vaccine or placebo at day 1, and at months 2 and 6. Ascertainment of CIN/EGL was accomplished through Pap testing, genital inspection, and cervicovaginal sampling (every 6 months). The main analysis was conducted in a per-protocol efficacy population (that received three doses, was naive to the relevant HPV types at day 1, and remained free of infection through month 7). Efficacy was also estimated in other naive and non-naive populations.Results:Vaccine efficacy against the combined incidence of persistent infection, CIN/EGL related to HPV6/11/16/18 in the per-protocol population was 88.7% (95% CI: 78.1, 94.8). Efficacy for women who were seropositive and DNA negative for the relevant vaccine HPV type at the time of enrolment who received at least 1 dose was 66.9% (95% CI: 4.3, 90.6). At month 48, 91.5, 92.0, 97.4, and 47.9% of vaccinated women were seropositive to HPV 6/11/16/18, respectively. No serious vaccine-related adverse experiences were reported.Conclusions:The qHPV vaccine demonstrated high efficacy, immunogenicity, and acceptable safety in women aged 24–45 years, regardless of previous exposure to HPV vaccine type.

Impact of human papillomavirus vaccination on anal cancer incidence in French women

“…Consequently, we did not include the need for vaccine booster shots in our model. The protective effect of vaccines is known to last at least several years and the need for boosters is currently unknown (Paavonen et al, 2009;Castellsague et al, 2011). Using deterministic modeling, our model took into account the "herd immunity" effect corresponding to a decrease in HPV 16/18 infections and anal cancers in non-vaccinated subpopulations of females due to vaccination coverage of other individuals.…”

“…In the basecase, we considered a high efficacy as observed in clinical trials which conducted statistical analyses in "per protocol" cohorts. The efficacy of vaccines in girls and young women who have never been infected with HPV is close to 100%, whereas efficacy drops significantly in "intention to treat" analyses (full cohort) (Rambout et al, 2007;Paavonen et al, 2009;Munoz et al, 2010;Castellsague et al, 2011). We therefore considered HPV vaccination with different levels of efficacy in sensitivity analyses.…”

Aspectos imunológicos da infecção pelo vírus do papiloma humano (HPV)

“…Já a vacina tetravalente apresenta VLP de HPV dos tipos 6, 11, 16 e 18, conferindo proteção à infecção e lesões citadas acima, assim como prevenção de verrugas genitais e lesões vulvares e vaginais (CUTTS et al, 2007;JOSÉ, 2008). Castellsagué et al (2011) demonstraram que a vacina tetravalente dos sorotipo, 6, 11, 16 e 18 recombinante apresentou imunogenicidade e eficácia em mulheres com 24 a 45 anos de idade.…”

Recommended immunization schedules for adults: Clinical practice guidelines by the Escmid Vaccine Study Group (EVASG), European Geriatric Medicine Society (EUGMS) and the World Association for Infectious Diseases and Immunological Disorders (WAidid)

“…37 The end-of-study results of a phase III efficacy, safety, and immunogenicity study involving the quadrivalent vaccine in women aged 24-45 y reported a vaccine efficacy against disease or infection related to HPV 6,11,16, and 18 in the accordingto-protocol (ATP) population of 88.7% (95% CI: 78.1, 94.8), and 66.9% (95% CI: 4.3, 90.6) in the intention-to-treat population (ITT), i.e., women who were seropositive and DNA negative for the HPV vaccine type at the time of enrolment, who received at least one dose of the vaccine. 38 In the intermediate analysis of this study, Munoz et al 39 reported a 30.9% (95% CI 11.1-46.5) efficacy of the quadrivalent vaccine against disease or infection related to HPV 6/11/16/18 in the ITT population, here including women aged 24-45 y with infection or disease present at baseline. This low percentage, with reference to the 90.5% (95% CI 73.7-97.5) efficacy observed in the ATP population, confirms that HPV vaccines are most effective when administered before exposure to HPV because they have no therapeutic effect and can only protect against HPV types not already acquired at the time of vaccination.…”