{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T03:51:42Z","timestamp":1782791502459,"version":"3.54.5"},"reference-count":54,"publisher":"American Academy of Pediatrics (AAP)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>The 9-valent human papillomavirus vaccine (9vHPV) was approved for females and males aged 9 to 26 years in 2014. We analyzed postlicensure surveillance reports to the Vaccine Adverse Event Reporting System (VAERS).<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>We searched VAERS data for US reports of adverse events (AEs) after 9vHPV from December 2014 through December 2017. We calculated reporting rates and conducted empirical Bayesian data mining to identify disproportional reporting. Physicians reviewed reports for selected prespecified conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>VAERS received 7244 reports after 9vHPV: 31.2% among females, 21.6% among males, and for 47.2%, sex was not reported. Overall, 97.4% of reports were nonserious. Dizziness, syncope, headache, and injection site reactions were most commonly reported; the most commonly reported AEs were similar between females and males. Two reports of death after 9vHPV were verified; no information in autopsy reports or death certificates suggested a causal relationship with vaccination. Approximately 28 million 9vHPV doses were distributed during the study period; crude AE reporting rates were 259 reports per million 9vHPV doses distributed for all reports and 7 per million doses distributed for serious reports. Syncope (a known AE associated with human papillomavirus vaccination) and several types of vaccine administration errors (eg, administered at wrong age) exceeded the statistical threshold for empirical Bayesian data mining findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>No new or unexpected safety concerns or reporting patterns of 9vHPV with clinically important AEs were detected. The safety profile of 9vHPV is consistent with data from prelicensure trials and from postmarketing safety data of its predecessor, the quadrivalent human papillomavirus vaccine.<\/jats:p><\/jats:sec>","DOI":"10.1542\/peds.2019-1791","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T13:24:20Z","timestamp":1574083460000},"source":"Crossref","is-referenced-by-count":61,"title":["Safety of the 9-Valent Human Papillomavirus Vaccine"],"prefix":"10.1542","volume":"144","author":[{"given":"Tom T.","family":"Shimabukuro","sequence":"first","affiliation":[{"name":"Division of Healthcare Quality Promotion, Immunization Safety Office, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Su","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Immunization Safety Office, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige L.","family":"Marquez","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Immunization Safety Office, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adamma","family":"Mba-Jonas","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge E.","family":"Arana","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Immunization Safety Office, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria V.","family":"Cano","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Immunization Safety Office, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2019,12,1]]},"reference":[{"key":"2021121018364684400_B1","volume-title":"Gardasil 9 [Package Insert]","author":"Merck & Co, Inc","year":"2014"},{"issue":"49","key":"2021121018364684400_B2","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.15585\/mmwr.mm6549a5","article-title":"Use of a 2-dose schedule for human papillomavirus vaccination - updated recommendations of the Advisory Committee on Immunization Practices","volume":"65","author":"Meites","year":"2016","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"11","key":"2021121018364684400_B3","first-page":"300","article-title":"Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the Advisory Committee on Immunization Practices","volume":"64","author":"Petrosky","year":"2015","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2021121018364684400_B4","first-page":"1","article-title":"Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP) [published correction appears in MMWR Recomm Rep. 2014;63(49):1182]","volume":"63","author":"Markowitz","year":"2014","journal-title":"MMWR Recomm Rep"},{"key":"2021121018364684400_B5","unstructured":"US Food and Drug Administration. Gardasil 9 [approval letter]. 2018. Available at: www.fda.gov\/downloads\/BiologicsBloodVaccines\/Vaccines\/ApprovedProducts\/UCM622718.pdf. Accessed July 23, 2019"},{"issue":"32","key":"2021121018364684400_bib54","doi-asserted-by":"crossref","first-page":"698","DOI":"10.15585\/mmwr.mm6832a3","article-title":"Human Papillomavirus Vaccination for Adults: Updated Recommendations of the Advisory Committee on Immunization Practices","volume":"68","author":"Meites","year":"2019","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"13","key":"2021121018364684400_B6","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1016\/j.vaccine.2018.02.034","article-title":"Post-licensure safety monitoring of quadrivalent human papillomavirus vaccine in the Vaccine Adverse Event Reporting System (VAERS), 2009-2015","volume":"36","author":"Arana","year":"2018","journal-title":"Vaccine"},{"issue":"7","key":"2021121018364684400_B7","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1001\/jama.2009.1201","article-title":"Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine","volume":"302","author":"Slade","year":"2009","journal-title":"JAMA"},{"issue":"46","key":"2021121018364684400_B8","doi-asserted-by":"crossref","first-page":"8279","DOI":"10.1016\/j.vaccine.2011.08.106","article-title":"Monitoring the safety of quadrivalent human papillomavirus vaccine: findings from the Vaccine Safety Datalink","volume":"29","author":"Gee","year":"2011","journal-title":"Vaccine"},{"key":"2021121018364684400_B9","doi-asserted-by":"crossref","first-page":"f5906","DOI":"10.1136\/bmj.f5906","article-title":"Autoimmune, neurological, and venous thromboembolic adverse events after immunisation of adolescent girls with quadrivalent human papillomavirus vaccine in Denmark and Sweden: cohort study","volume":"347","author":"Arnheim-Dahlstr\u00f6m","year":"2013","journal-title":"BMJ"},{"issue":"9","key":"2021121018364684400_B10","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1097\/INF.0000000000000793","article-title":"An overview of quadrivalent human papillomavirus vaccine safety: 2006 to 2015","volume":"34","author":"Vichnin","year":"2015","journal-title":"Pediatr Infect Dis J"},{"issue":"2","key":"2021121018364684400_B11","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/j.1365-2796.2011.02467.x","article-title":"Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine","volume":"271","author":"Chao","year":"2012","journal-title":"J Intern Med"},{"issue":"1","key":"2021121018364684400_B12","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1001\/jama.2014.16946","article-title":"Quadrivalent HPV vaccination and risk of multiple sclerosis and other demyelinating diseases of the central nervous system","volume":"313","author":"Scheller","year":"2015","journal-title":"JAMA"},{"issue":"6","key":"2021121018364684400_B13","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1080\/21645515.2016.1168952","article-title":"Quadrivalent HPV vaccine safety review and safety monitoring plans for nine-valent HPV vaccine in the United States","volume":"12","author":"Gee","year":"2016","journal-title":"Hum Vaccin Immunother"},{"issue":"8","key":"2021121018364684400_B14","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1405044","article-title":"A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women","volume":"372","author":"Joura","year":"2015","journal-title":"N Engl J Med"},{"issue":"1","key":"2021121018364684400_B15","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2014-3745","article-title":"Immunogenicity and safety of a 9-valent HPV vaccine","volume":"136","author":"Van Damme","year":"2015","journal-title":"Pediatrics"},{"issue":"2","key":"2021121018364684400_B16","doi-asserted-by":"crossref","first-page":"e20154387","DOI":"10.1542\/peds.2015-4387","article-title":"Safety profile of the 9-valent HPV vaccine: a combined analysis of 7 phase III clinical trials","volume":"138","author":"Moreira","year":"2016","journal-title":"Pediatrics"},{"key":"2021121018364684400_B17","volume-title":"Gardasil [package insert]","author":"Merck & Co, Inc","year":"2006"},{"issue":"36","key":"2021121018364684400_B18","doi-asserted-by":"crossref","first-page":"4398","DOI":"10.1016\/j.vaccine.2015.07.035","article-title":"Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS)","volume":"33","author":"Shimabukuro","year":"2015","journal-title":"Vaccine"},{"key":"2021121018364684400_B19","unstructured":"Medical Dictionary for Regulatory Activities. MedDRA. Available at: www.meddra.org\/. Accessed July 23, 2019"},{"key":"2021121018364684400_B20","unstructured":"US Food and Drug Administration. Code of Federal Regulations title 21, volume 7 (21CFR600.80). Available at: www.accessdata.fda.gov\/scripts\/cdrh\/cfdocs\/cfcfr\/CFRSearch.cfm?fr=600.80. Accessed July 23, 2019"},{"key":"2021121018364684400_B21","unstructured":"European Medicines Agency. (EMA\/762033\/2015) Pharmacovigilance Risk Assessment Committee. Assessment report: review under article 20 of regulation (EC) No 726\/2004, human papillomavirus (HPV) vaccines. 2015. Available at: https:\/\/www.ema.europa.eu\/documents\/variation-report\/silgard-h-c-732-a20-1421-epar-assessment-report-article-20_en.pdf. Accessed July 23, 2019"},{"issue":"31","key":"2021121018364684400_B22","doi-asserted-by":"crossref","first-page":"5675","DOI":"10.1016\/j.vaccine.2007.02.064","article-title":"Anaphylaxis: case definition and guidelines for data collection, analysis, and presentation of immunization safety data","volume":"25","author":"R\u00fcggeberg","year":"2007","journal-title":"Vaccine"},{"issue":"3","key":"2021121018364684400_B23","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.vaccine.2010.06.003","article-title":"Guillain-Barr\u00e9 syndrome and Fisher syndrome: case definitions and guidelines for collection, analysis, and presentation of immunization safety data","volume":"29","author":"Sejvar","year":"2011","journal-title":"Vaccine"},{"issue":"23","key":"2021121018364684400_B24","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1161\/CIRCULATIONAHA.112.144501","article-title":"Postural tachycardia syndrome (POTS)","volume":"127","author":"Raj","year":"2013","journal-title":"Circulation"},{"key":"2021121018364684400_B25","volume-title":"A Randomised Placebo-Controlled Phase III Multicentre Trial: Low-Dose Intravenous Immunoglobulin Treatment for Long-Standing Complex Regional Pain Syndrome (LIPS Trial)","author":"Goebel","year":"2017"},{"issue":"1","key":"2021121018364684400_B26","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1097\/01.AOG.0000451757.51964.98","article-title":"Committee opinion no. 605: primary ovarian insufficiency in adolescents and young women","volume":"124","year":"2014","journal-title":"Obstet Gynecol"},{"issue":"6","key":"2021121018364684400_B27","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1056\/NEJMcp0808697","article-title":"Clinical practice. Primary ovarian insufficiency","volume":"360","author":"Nelson","year":"2009","journal-title":"N Engl J Med"},{"issue":"9","key":"2021121018364684400_B28","doi-asserted-by":"crossref","first-page":"S38","DOI":"10.1212\/WNL.0000000000002825","article-title":"Acute disseminated encephalomyelitis: updates on an inflammatory CNS syndrome","volume":"87","author":"Pohl","year":"2016","journal-title":"Neurology"},{"issue":"24","key":"2021121018364684400_B29","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1212\/WNL.0b013e31823dc535","article-title":"Evidence-based guideline: clinical evaluation and treatment of transverse myelitis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology","volume":"77","author":"Scott","year":"2011","journal-title":"Neurology"},{"issue":"8","key":"2021121018364684400_B30","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.1212\/WNL.60.8_suppl_3.S8","article-title":"Research criteria for defining patients with CIDP","volume":"60","author":"Sander","year":"2003","journal-title":"Neurology"},{"issue":"7","key":"2021121018364684400_B31","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s40264-013-0051-9","article-title":"Data mining for prospective early detection of safety signals in the Vaccine Adverse Event Reporting System (VAERS): a case study of febrile seizures after a 2010-2011 seasonal influenza virus vaccine","volume":"36","author":"Martin","year":"2013","journal-title":"Drug Saf"},{"issue":"3","key":"2021121018364684400_B32","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1080\/00031305.1999.10474456","article-title":"Bayesian data mining in large frequency tables, with an application to the FDA spontaneous reporting system","volume":"53","author":"DuMouchel","year":"1999","journal-title":"Am Stat"},{"issue":"6","key":"2021121018364684400_B33","doi-asserted-by":"crossref","first-page":"381","DOI":"10.2165\/00002018-200225060-00001","article-title":"Use of screening algorithms and computer systems to efficiently signal higher-than-expected combinations of drugs and events in the US FDA\u2019s spontaneous reports database","volume":"25","author":"Szarfman","year":"2002","journal-title":"Drug Saf"},{"key":"2021121018364684400_B34","first-page":"620","volume-title":"Adverse Effects of Vaccines: Evidence and Causality","author":"Institute of Medicine","year":"2012"},{"issue":"12","key":"2021121018364684400_B35","doi-asserted-by":"crossref","first-page":"2928","DOI":"10.1111\/bcp.13736","article-title":"Safety of bivalent human papillomavirus vaccine in the US Vaccine Adverse Event Reporting System (VAERS), 2009-2017","volume":"84","author":"Suragh","year":"2018","journal-title":"Br J Clin Pharmacol"},{"issue":"10","key":"2021121018364684400_B36","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1016\/j.vaccine.2012.10.097","article-title":"U.S. Postlicensure safety surveillance for adolescent and adult tetanus, diphtheria and acellular pertussis vaccines: 2005-2007","volume":"31","author":"Chang","year":"2013","journal-title":"Vaccine"},{"issue":"14","key":"2021121018364684400_B37","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1016\/j.vaccine.2017.02.030","article-title":"Adverse events following quadrivalent meningococcal CRM-conjugate vaccine (Menveo\u00ae) reported to the Vaccine Adverse Event Reporting System (VAERS), 2010-2015","volume":"35","author":"Myers","year":"2017","journal-title":"Vaccine"},{"issue":"22","key":"2021121018364684400_B38","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1016\/j.vaccine.2016.03.048","article-title":"Post-licensure surveillance of quadrivalent inactivated influenza (IIV4) vaccine in the United States, Vaccine Adverse Event Reporting System (VAERS), July 1, 2013-May 31, 2015","volume":"34","author":"Haber","year":"2016","journal-title":"Vaccine"},{"issue":"27","key":"2021121018364684400_B39","first-page":"577","article-title":"Intussusception among recipients of rotavirus vaccine\u2013United States, 1998-1999","volume":"48","author":"Centers for Disease Control and Prevention (CDC)","year":"1999","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"11","key":"2021121018364684400_B40","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1016\/j.vaccine.2011.12.042","article-title":"Febrile seizures after 2010-2011 influenza vaccine in young children, United States: a vaccine safety signal from the Vaccine Adverse Event Reporting System","volume":"30","author":"Leroy","year":"2012","journal-title":"Vaccine"},{"issue":"7","key":"2021121018364684400_B41","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1093\/cid\/ciy232","article-title":"National trends in parental human papillomavirus vaccination intentions and reasons for hesitancy, 2010-2015","volume":"67","author":"Hanson","year":"2018","journal-title":"Clin Infect Dis"},{"issue":"6","key":"2021121018364684400_B42","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1080\/21645515.2016.1157673","article-title":"Comparing human papillomavirus vaccine knowledge and intentions among parents of boys and girls","volume":"12","author":"Lindley","year":"2016","journal-title":"Hum Vaccin Immunother"},{"key":"2021121018364684400_B43","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.acap.2017.09.014","article-title":"Ten years of human papillomavirus vaccination in the United States","volume":"18","author":"Markowitz","year":"2018","journal-title":"Acad Pediatr"},{"issue":"4","key":"2021121018364684400_B44","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s40264-017-0625-z","article-title":"Safety of human papillomavirus vaccines: an updated review","volume":"41","author":"Phillips","year":"2018","journal-title":"Drug Saf"},{"issue":"25","key":"2021121018364684400_B45","doi-asserted-by":"crossref","first-page":"3778","DOI":"10.1016\/j.vaccine.2011.11.112","article-title":"Anti-vaccine activists, Web 2.0, and the postmodern paradigm\u2013an overview of tactics and tropes used online by the anti-vaccination movement","volume":"30","author":"Kata","year":"2012","journal-title":"Vaccine"},{"issue":"1","key":"2021121018364684400_B46","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1097\/GCO.0000000000000240","article-title":"Human papillomavirus vaccination and primary ovarian insufficiency: an association based on ideology rather than evidence","volume":"28","author":"Hawkes","year":"2016","journal-title":"Curr Opin Obstet Gynecol"},{"issue":"11","key":"2021121018364684400_B47","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1177\/0883073817718731","article-title":"Human papillomavirus vaccine and postural orthostatic tachycardia syndrome: a review of current literature","volume":"32","author":"Butts","year":"2017","journal-title":"J Child Neurol"},{"issue":"6","key":"2021121018364684400_B48","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1016\/j.jaip.2017.06.033","article-title":"Evidence refuting the existence of autoimmune\/autoinflammatory syndrome induced by adjuvants (ASIA)","volume":"5","author":"Ameratunga","year":"2017","journal-title":"J Allergy Clin Immunol Pract"},{"key":"2021121018364684400_B49","first-page":"1127","volume-title":"The Autoimmune Diseases","author":"Mackay","year":"2013"},{"issue":"5","key":"2021121018364684400_B50","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.jadohealth.2017.08.004","article-title":"Reports of postural orthostatic tachycardia syndrome after human papillomavirus vaccination in the Vaccine Adverse Event Reporting System","volume":"61","author":"Arana","year":"2017","journal-title":"J Adolesc Health"},{"issue":"3","key":"2021121018364684400_B51","doi-asserted-by":"crossref","first-page":"e20180943","DOI":"10.1542\/peds.2018-0943","article-title":"Primary ovarian insufficiency and adolescent vaccination","volume":"142","author":"Naleway","year":"2018","journal-title":"Pediatrics"},{"key":"2021121018364684400_B52","unstructured":"Ezeanolue\u2008E, Harriman\u2008K, Hunter\u2008P, Kroger\u2008A, Pellegrini\u2008C. General best practice guidelines for immunization: best practices guidance of the Advisory Committee on Immunization Practices (ACIP). Available at: www.cdc.gov\/vaccines\/hcp\/acip-recs\/general-recs\/downloads\/general-recs.pdf. Accessed July 23, 2019"},{"issue":"6","key":"2021121018364684400_B53","doi-asserted-by":"crossref","first-page":"e20191808","DOI":"10.1542\/peds.2019-1808","article-title":"Near real-time surveillance to assess the safety of the 9-valent human papillomavirus vaccine","volume":"144","author":"Donahue","year":"2019","journal-title":"Pediatrics"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/doi\/10.1542\/peds.2019-1791\/1078296\/peds_20191791.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/doi\/10.1542\/peds.2019-1791\/1078296\/peds_20191791.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T03:33:16Z","timestamp":1722051196000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/144\/6\/e20191791\/37909\/Safety-of-the-9-Valent-Human-Papillomavirus"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,1]]},"references-count":54,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,12,1]]},"published-print":{"date-parts":[[2019,12,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2019-1791","relation":{},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,1]]},"article-number":"e20191791"}}