title: An Overview of Quadrivalent Human Papillomavirus Vaccine Safety: 2006 to 2015.
abstract: 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.
authors.affiliation: 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.
authors.forename: Michelle
authors.initials: M
authors.lastname: Vichnin
authors.forename: Paolo
authors.initials: P
authors.lastname: Bonanni
authors.forename: Nicola P
authors.initials: NP
authors.lastname: Klein
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Garland
authors.forename: Stan L
authors.initials: SL
authors.lastname: Block
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Kjaer
authors.forename: Heather L
authors.initials: HL
authors.lastname: Sings
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Perez
authors.forename: Richard M
authors.initials: RM
authors.lastname: Haupt
authors.forename: Alfred J
authors.initials: AJ
authors.lastname: Saah
authors.forename: Fabio
authors.initials: F
authors.lastname: Lievano
authors.forename: Christine
authors.initials: C
authors.lastname: Velicer
authors.forename: Rosybel
authors.initials: R
authors.lastname: Drury
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Kuter
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000473:pathology*; D005260:Female; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18 / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000517:prevention & control*; D011247:Pregnancy; D011358:Product Surveillance, Postmarketing; D055815:Young Adult
chemical_list: D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18