Sustained immunogenicity and efficacy of the HPV-16/18 AS04-adjuvanted vaccine

Abstract

Prophylactic human papillomavirus (HPV) vaccines are now available and vaccination programs are being widely implemented, targeting adolescent girls prior to sexual debut. Since the risk of HPV exposure persists throughout a woman’s sexual life, the duration of protection provided by vaccination is critical to the overall vaccine effectiveness. We report the long-term efficacy and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine (Cervarix^®) up to 8.4 y after the first vaccine dose.

 

In an initial placebo-controlled study performed in US, Canada and Brazil, women aged 15–25 y with normal cervical cytology, HPV-16/18 seronegative by ELISA, DNA-negative for 14 oncogenic HPV types by PCR, received either the HPV-16/18 vaccine or placebo (n = 1,113). Subjects were followed up to 6.4 y after the first dose (n = 776). We report an additional 2-y follow-up for women enrolled from the Brazilian centers from the initial study (n = 436).

During the current follow-up study (HPV-023, NCT00518336), no new infection or lesions associated with HPV-16/18 occurred in the vaccine group. Vaccine efficacy over the entire follow-up (up to 8.4 y) was 95.1% (84.6, 99.0) for incident infection, 100% (79.8, 100) for 6-mo persistent infection, 100% (56.1, 100) for 12-mo persistent infection and 100% (< 0, 100) for CIN2+ associated with HPV-16/18. All women in the vaccine group remained seropositive to both HPV-16/18, with antibody titers for total and neutralizing antibodies remaining several-folds above natural infection levels. The safety profile was clinically acceptable for both vaccine and control groups. This is, to date, the longest follow-up study for a licensed cervical cancer vaccine.

Keywords: :

• HPV-16/18 vaccine
• Human papillomavirus (HPV)
• cervical cancer
• efficacy
• long-term immunogenicity
• prophylactic

Acknowledgments

We would like to thank the study participants and the staff members of the study sites of this study. Laboratory work was provided by W. Quint, L.-J. Van Doorn and A. Molijn (DDL Diagnostic Laboratory, Voorburg, The Netherlands); R. Luff, M. McNeeley, E. Alt, B. Iskaros, A. Limaye, X. Jarin, C. Provenzano and B. Winkler (Quest Diagnostics, Teterboro, NJ, USA); A. Meurée, R. Crudenaire and S. Poncelet (GlaxoSmithKline Biologicals, Rixensart, Belgium). From GlaxoSmithKline Biologicals, we also thank A. Vanneuville and M. Lojo Suarez for global study management and Stéphanie Genevrois for scientific writing of the clinical study report. Finally, we would like to thank Catherine Streeton (Streeton Associates) who provided medical writing services on behalf of GlaxoSmithKline Biologicals, and Jean-Michel Heine (Keyrus Biopharma) and Denis Sohy (Business and Decision) for editorial assistance and manuscript coordination.

Disclosure of Potential Conflicts of Interest

C. Roteli-Martins, P. Naud, P. De Borba, J. Teixeira and N. De Carvalho received funding and/or equipment/administrative support through their institutions from GlaxoSmithKline Biologicals. C. Roteli-Martins, P. Naud, P. De Borba, J. Teixeira and N. De Carvalho received support for travel to meetings from GlaxoSmithKline Biologicals. C. M Roteli-Martins, P. De Borba, J. Teixeira and N. De Carvalho received fees for participation in advisory boards and/or lectures from GlaxoSmithKline Biologicals. P. Naud received consulting fee/honorarium from GlaxoSmithKline Biologicals. N. Sanchez, T. Zahaf, B. Geeraerts and D. Descamps are employees of GlaxoSmithKline Biologicals, N. Sanchez and D. Descamps hold stock options from GlaxoSmithKline Biologicals.

Note

*Cervarix^® is a registered trademark of the GlaxoSmithKline group of companies.