Background: A quadrivalent human papillomavirus (HPV4) type 6/11/16/18 vaccine (GARDASIL/SILGARD®) has been licensed in many countries around the world for the prevention of cervical, vulvar, vaginal, and anal cancers and precancers, as well as external genital warts causally related to HPV types 6/11/16/18. Across 7 phase 3 clinical trials involving more than 29,000 males and females ages 9–45 years, vaccination was generally well tolerated. Because of its expected public health benefit in reducing cervical cancer and other HPV-related diseases, the vaccine has been implemented in the national vaccination programs of several countries, with over 178 million doses distributed worldwide.
Methods: Extensive efforts to assess the safety of the vaccine in routine practice have been conducted over the past 9 years since licensure, including more than 15 studies in more than 1 million preadolescents, adolescents and adults from various countries. Most have been performed in the general population although there have been some in special populations (pregnant women, HIV-infected individuals and those with systemic lupus erythematosus).
Results: We present a summary of the published, postlicensure safety data from active and passive surveillance. Only syncope, and possibly skin infections were associated with vaccination in the postlicensure setting. Serious adverse events, such as adverse pregnancy outcomes, autoimmune diseases (including Guillain–Barre Syndrome and multiple sclerosis), anaphylaxis, venous thromboembolism and stroke, were extensively studied, and no increase in the incidence of these events was found compared with background rates.
Conclusions: These results, along with the safety data from the prelicensure clinical trials, confirm that the HPV4 vaccine has a favorable safety profile. Key policy, medical and regulatory organizations around the world have independently reviewed these data and continue to recommend routine HPV vaccination.
From the *Merck & Co., Inc., Kenilworth, New Jersey; †University of Florence, Florence, Italy; ‡Kaiser Permanente Vaccine Study Center, Oakland, California; §The Royal Women’s’ Hospital, Murdoch Childrens Research Institute, University of Melbourne, Parkville, Victoria, Australia; ¶Kentucky Pediatric Research, Inc., Bardstown, Kentucky; ‖Danish Cancer Society Research Center, Copenhagen, Denmark; **Department of Gynaecology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; ††Universidad del Rosario, Bogota, Colombia; and ‡‡Sanofi Pasteur MSD, Lyon, France.
Accepted for publication March 5, 2015.
The authors declare the following: Paolo Bonanni reports having received grant support from Sanofi Pasteur MSD and GlaxoSmithKline; reimbursements, advisory boards, consultancy and lecture fees from Sanofi Pasteur MSD and GlaxoSmithKline. Nicola P. Klein reports having received research support from Merck, GlaxoSmithKline, Pfizer, Novartis, Sanofi Pasteur, MedImmune and Nuron Biotech. Suzanne M. Garland reports having received grant support from Merck, GlaxoSmithKline and CSL; reimbursement fare for attending a global advisory board from Merck, and lecture fees from Sanofi Pasteur. Stan Block reports having received grant support, and speaker fees from Merck and research grants from GlaxoSmithKline. Susanne K. Kjaer reports having received scientific advisory board and speaker’s fees and unrestricted research grants through her institution from Sanofi Pasteur MSD and Merck, and scientific advisory board fee from Roche. Michelle Vichnin, Heather L Sings, Gonzalo Perez, Richard M. Haupt, Alfred Saah, Fabio Lievano, Christine Velicer, and Barbara J. Kuter are current or former Merck employees and hold stock/stock options. Rosybel Drury is an employee of Sanofi Pasteur MSD.
All authors were involved with the design, analysis or interpretation of the data, the writing of the manuscript, and approved the final version to be submitted. All agree to be accountable for all aspects of the work.
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Address for correspondence: Michelle Vichnin, MD, Merck & Co., 2000 Galloping Hill Road, Kenilworth, NJ 07033. E-mail: firstname.lastname@example.org.