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

X Castellsagué, N Muñoz, P Pitisuttithum, D Ferris, J Monsonego, K Ault, J Luna, E Myers, S Mallary, O M Bautista, J Bryan, S Vuocolo, R M Haupt, A Saah, X Castellsagué, N Muñoz, P Pitisuttithum, D Ferris, J Monsonego, K Ault, J Luna, E Myers, S Mallary, O M Bautista, J Bryan, S Vuocolo, R M Haupt, A Saah

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.

Conflict of interest statement

XC has received travel and speaker honoraria and investigator grants from Merck & Co. Inc., GlaxoSmithKline, and Sanofi-Pasteur MSD. NM has received honoraria from Merck & Co. Inc. and Sanofi-Pasteur MSD and is a member of the Merck global advisory board for HPV vaccine, as well as a member of Sanofi-Pasteur MSD HPV steering committee. JL has received travel and speaker and investigator grants from Sanofi-Pasteur MSD. JM has conducted HPV vaccine studies for Merck & Co. Inc. and GlaxoSmithKline, and is on the medical advisory board for GlaxoSmithKline, Geneprobe, Sanofi-Pasteur MSD, Roche, and Abbott diagnostics. KA has conducted HPV vaccine studies for Merck & Co. Inc. and GlaxoSmithKline, and as acted as a consultant to Merck & Co. Inc. EM has served as a consultant to Merck & Co. Inc. NM, JL, KA, JM, and EM are members of the Merck & Co. Inc. HPV steering committee. OMB, SM, JB, SV, AS, and RMH are employees of Merck & Co. Inc. and potentially own stock and/or stock options in the company. DF has conducted HPV vaccine studies for Merck & Co. Inc. and GlaxoSmithKline, and is a speaker and on the medical advisory board for Merck & Co. Inc. Funding: Merck & Co. Inc.

Figures

Figure 1
Figure 1
Summary of the persistence of anti-HPV geometric mean titres (GMTs) in women receiving the qHPV vaccine (also see Supplementary Figure 1 stratified by baseline vaccine-type serostatus). The dots shown the in plot correspond to estimates of GMTs. The vertical bars superimposed to each dot represent the 95% confidence interval associated with the estimated GMT. The mini-vertical axes immediately to the left of the vertical bars show the range of the 95% confidence interval specific to each GMT estimate. The length of each vertical bar is relative only to the mini-scale immediately to the left of the vertical bar. The length of the vertical bars across time points is not comparable. Comparisons of statistically significant difference or absence of statistically significant difference between GMTs over time should not be made on the basis of comparisons of the length of the vertical bars. The antibody titres for the placebo group were within the margin of error for the assay and were not plotted.

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