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Clinical Trial
. 2015 Jul;16(7):775-86.
doi: 10.1016/S1470-2045(15)00047-9. Epub 2015 Jun 9.

Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined analysis of data from the Costa Rica Vaccine and PATRICIA Trials

Aimée R Kreimer  1 , Frank Struyf  2 , Maria Rowena Del Rosario-Raymundo  3 , Allan Hildesheim  4 , S Rachel Skinner  5 , Sholom Wacholder  4 , Suzanne M Garland  6 , Rolando Herrero  7 , Marie-Pierre David  2 , Cosette M Wheeler  8 ; Costa Rica Vaccine Trial Study Group Authors; Paula González, Silvia Jiménez, Douglas R Lowy, Ligia A Pinto, Caroline Porras, Ana Cecilia Rodriguez, Mahboobeh Safaeian, Mark Schiffman, John T Schiller, John Schussler, Mark E Sherman; PATRICIA Study Group Authors; F Xavier Bosch, Xavier Castellsague, Archana Chatterjee, Song-Nan Chow, Dominique Descamps, Francisco Diaz-Mitoma, Gary Dubin, Maria Julieta Germar, Diane M Harper, David J M Lewis, Genara Limson, Paulo Naud, Klaus Peters, Willy A J Poppe, Brian Ramjattan, Barbara Romanowski, Jorge Salmeron, Tino F Schwarz, Julio C Teixeira, Wiebren A A Tjalma; HPV PATRICIA Principal Investigators/Co-Principal Investigator Collaborators; GSK Vaccines Clinical Study Support Group
Collaborators, Affiliations
Clinical Trial

Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined analysis of data from the Costa Rica Vaccine and PATRICIA Trials

Aimée R Kreimer et al. Lancet Oncol. 2015 Jul.

Abstract

Background: There is some evidence to suggest that one or two doses of the HPV vaccine provides similar protection to the three-dose regimen. The main aim of the study was to ascertain HPV-16/18 vaccine efficacy in both full and naive cohorts and to explore protection conferred against non-vaccine HPV types, by number of doses received.

Methods: Summary data from the Costa Rica Vaccine Trial (CVT; NCT00128661) and ~the PATRICIA trial (NCT001226810), two phase 3, double-blind, randomised controlled clinical trials of the HPV-16/18 AS04-adjuvanted vaccine in young women, were combined in a post-hoc analysis (GlaxoSmithKline [GSK] e-track number 202142) to investigate the efficacy of fewer than three doses of the HPV-16/18 vaccine after 4 years of follow-up. Women were randomly assigned to receive three doses of the HPV-16/18 vaccine or to a control vaccine; yet, some received fewer doses. After exclusion of women with less than 12 months of follow-up or those who were HPV-16/18 DNA-positive at enrolment (for the HPV-16/18 endpoint), we calculated vaccine efficacy against one-time detection of incident HPV infections after three, two, and one dose(s). The primary study endpoint was one-time detection of first incident HPV-16/18 infections accumulated during the follow-up phase.

Findings: We assessed vaccine efficacy against incident HPV-16/18 infection in the modified total vaccinated cohort (22 327 received three doses, 1185 two doses, 543 one dose). Vaccine efficacy against incident HPV-16/18 infections for three doses was 77·0% (95% CI 74·7-79·1), two doses was 76·0% (62·0-85·3), and one dose was 85·7% (70·7-93·7). Vaccine efficacy against incident HPV-31/33/45 infections for three doses was 59·7% (56·0-63·0), two doses was 37·7% (12·4-55·9), and one dose was 36·6% (-5·4 to 62·2). Vaccine efficacy against incident HPV-16/18 infection for two-dose women who received their second dose at 1 month was 75·3% (54·2-87·5) and 82·6% (42·3-96·1) for those who received the second dose at 6 months (CVT data only). Vaccine efficacy against HPV-31/33/45 for two-dose women who received their second dose at 6 months (68·1%, 27·0-87·0; CVT data only), but not those receiving it at one month (10·1%, -42·0 to 43·3), was similar to the three-dose group.

Interpretation: 4 years after vaccination of women aged 15-25 years, one and two doses of the HPV-16/18 vaccine seem to protect against cervical HPV-16/18 infections, similar to the protection provided by the three-dose schedule. Two doses separated by 6 months additionally provided some cross-protection. These data argue for a direct assessment of one-dose efficacy of the HPV-16/18 vaccine.

Funding: US National Cancer Institute, National Institutes of Health Office of Research on Women's Health, and Ministry of Health of Costa Rica (CVT); GlaxoSmithKline Biologicals SA (PATRICIA).

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Figures

Figure 1
Figure 1. CONSORT diagram for the Costa Rica Vaccine Trial and PATRICIA trial combined
This CONSORT contains women who were randomized into both trials, stratified by vaccine arm and number of doses received. 1Women were excluded if they had less than 12 months follow-up time (time total vaccinated cohort, T-TVC). 2Women were additionally excluded if their enrollment cervical status was HPV16 AND 18 DNA-positive (or missing) or they had fewer than 300 days between first and last PCR result; modified total vaccinated cohort (M-TVC) evaluating HPV16/18-related endpoints. 3Women were further excluded from the TVC-naïve if their cervical status at enrollment was HPV DNA-positive for any oncogenic type (or missing), or HPV16 or 18 seropositive (or missing), or had enrollment cytology abnormal (or missing).
Figure 2
Figure 2
Vaccine efficacy by study (CVT and PATRICIA) for multiple endpoints in the modified total vaccinated cohort, by dose (M-TVC).
Figure 3
Figure 3
Vaccine efficacy for individual HPV types by dose, for incident HPV infections that were detected one time (panel A), that persisted 6+ months (panel B), and that persisted 12+ months (panel C) (M-TVC).
See this image and copyright information in PMC

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