Edson D. Moreira Jr, MD, PhD, a Stan L. Block, MD, b Daron Ferris, MD, c Anna R. Giuliano, PhD, d Ole-Erik Iversen, MD, e Elmar A. Joura, MD, f Pope Kosalaraksa, MD, g Andrea Schilling, MD, h Pierre Van Damme, MD, PhD, i Jacob Bornstein, MD, MPA, j F. Xavier Bosch, MD, k Sophie Pils, MD, f Jack Cuzick, PhD, l Suzanne M. Garland, MD, m Warner Huh, MD, n Susanne K. Kjaer, MD, o Hong Qi, MD, MPH, p Donna Hyatt, BA, p Jason Martin, MS, p Erin Moeller, MPH, p Michael Ritter, BA, p Martine Baudin, MD, q Alain Luxembourg, MD, PhDp. aAssociação Obras Sociais Irmã Dulce and Oswaldo Cruz Foundation, Brazilian Ministry of Health, Bahia, Brazil; bKentucky Pediatric/Adult Research, Inc, Bardstown, Kentucky; cDepartment of Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia; dCenter for Infection Research in Cancer, Moffi tt Cancer Center, Tampa, Florida; eDepartment of Gynaecology, University of Bergen, Bergen, Norway; fDepartment of Obstetrics, Medical University of Vienna, Vienna, Austria; gDepartment of Medicine, Khon Kaen University, Khon Kaen, Thailand; hDepartamento de Ginecología y Obstetricia Clínica Alemana, Facultad de Medicina Clínica Alemana— Universidad Del Desarrollo, Santiago, Chile; iCentre for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium; jDepartment of Obstetrics and Gynecology, Galilee Medical Center and Bar Ilan University Faculty of Medicine, Nahariya, Israel; kCatalan Institute of Oncology/ IDIBELL, Barcelona, Spain; lWolfson Institute of Preventive Medicine, London, United Kingdom; mRoyal Women’s Hospital, University of Melbourne and Murdoch Childrens Research Institute, Parkville, Australia; nDivision of Gynecologic Oncology, University of Alabama Birmingham, Birmingham, Alabama; oDanish Cancer Society Research Center and Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; pMerck & Co., Inc., Kenilworth, New Jersey; and qSanofi Pasteur MSD, Lyon, France.Merck & Co., Inc., Kenilworth, New JerseyThe overall safety profile of the 9-valent human papillomavirus (9vHPV) vaccine was evaluated across 7 Phase III studies, conducted in males and females (nonpregnant at entry), 9 to 26 years of age. METHODS: Vaccination was administered as a 3-dose regimen at day 1, and months 2 and 6. More than 15 000 subjects received ≥1 dose of 9vHPV vaccine. In 2 of the studies, >7000 control subjects received ≥1 dose of quadrivalent HPV (qHPV) vaccine. Serious and nonserious adverse events (AEs) and new medical conditions were recorded throughout the study. Subjects testing positive for pregnancy at day 1 were not vaccinated; those who became pregnant after day 1 were discontinued from further vaccination until resolution of the pregnancy. Pregnancies detected after study start (n = 2950) were followed to outcome. RESULTS: The most common AEs (≥5%) experienced by 9vHPV vaccine recipients were injection-site AEs (pain, swelling, erythema) and vaccine-related systemic AEs (headache, pyrexia). Injection-site AEs were more common in 9vHPV vaccine than qHPV vaccine recipients; most were mild-to-moderate in intensity. Discontinuations and vaccine-related serious AEs were rare (0.1% and <0.1%, respectively). Seven deaths were reported; none were considered vaccine related. The proportions of pregnancies with adverse outcome were within ranges reported in the general population. CONCLUSIONS: The 9vHPV vaccine was generally well tolerated in subjects aged 9 to 26 years with an AE profile similar to that of the qHPV vaccine; injection-site AEs were more common with 9vHPV vaccine. Its additional coverage and safety profile support widespread 9vHPV vaccination.2017-08-31