Efficacy of the HPV-16/18 vaccine: Final according to protocol results from the blinded phase of the randomized Costa Rica HPV-16/18 vaccine trial

Allan Hildesheim, Sholom Wacholder, Gregory Catteau, Frank Struyf, Gary Dubin, Rolando Herrero, Mario Alfaro, M. Concepción Bratti, Bernal Cortés, Albert Espinoza, Yenory Estrada, Paula González, Diego Guil-Lén, Silvia E. Jiménez, Jorge Morales, Lidia Ana Morera, Carolina Porras, Ana Cecilia Rodríguez, Luis Villegas, Enrique FreerJosé Bonilla, Aimée R. Kreimer, Douglas R. Lowy, Nora Macklin, Mark Schiffman, John T. Schiller, Mark Sherman, Diane Solomon, Ligia Pinto, Troy Kemp, Mary Sidawy, Wim Quint, Leen Jan van Doorn

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


Background: A community-based randomized trial was conducted in Costa Rica to evaluate the HPV-16/18 AS04-adjuvanted vaccine ( NCT00128661). The primary objective was to evaluate efficacy of the vaccine to prevent cervical intraepithelial neoplasia 2 or more severe disease (CIN2+) associated with incident HPV-16/18 cervical infections. Secondary objectives were to evaluate efficacy against CIN2+ associated with incident cervical infection by any oncogenic HPVs and to evaluate duration of protection against incident cervical infection with HPV-16/18. Vaccine safety and immunogenicity over the 4-year follow-up were also evaluated. Methods: We randomized (3727 HPV arm; 3739 control arm), vaccinated (HPV-16/18 or Hepatitis A) and followed (median 53.8 months) 7466 healthy women aged 18-25 years. 5312 women (2635 HPV arm; 2677 control arm) were included in the according to protocol analysis for efficacy. The full cohort was evaluated for safety. Immunogenicity was considered on a subset of 354 (HPV-16) and 379 (HPV-18) women. HPV type was assessed by PCR on cervical specimens. Immunogenicity was assessed using ELISA and inhibition enzyme immunoassays. Disease outcomes were histologically confirmed. Vaccine efficacy and 95% confidence intervals (95%CI) were computed. Results: Vaccine efficacy was 89.8% (95% CI: 39.5-99.5; N = 11 events total) against HPV-16/18 associated CIN2+, 59.9% (95% CI: 20.7-80.8; N = 39 events total) against CIN2+ associated with non-HPV-16/18 oncogenic HPVs and 61.4% (95% CI: 29.5-79.8; N= 51 events total) against CIN2+ irrespective of HPV type. The vaccine had an acceptable safety profile and induced robust and long-lasting antibody responses. Conclusions: Our findings confirm the high efficacy and immunogenicity of the HPV-16/18 vaccine against incident HPV infections and cervical disease associated with HPV-16/18 and other oncogenic HPV types. These results will serve as a benchmark to which we can compare future findings from the ongoing extended follow-up of participants in the Costa Rica trial. Trial registration:: Registered with clinicaltrials.gov: NCT00128661.

Original languageEnglish (US)
Pages (from-to)5087-5097
Number of pages11
Issue number39
StatePublished - Sep 3 2014


  • Cervical neoplasia
  • Clinical trial
  • Human papillomaviruses
  • Prevention
  • Vaccination

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases


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