title: Monitoring the safety of quadrivalent human papillomavirus vaccine: findings from the Vaccine Safety Datalink.
abstract: BACKGROUND
  In 7 large managed care organizations (MCOs), we performed a post-licensure safety assessment of quadrivalent human papillomavirus vaccine (HPV4) among 9-26 year-old female vaccine recipients between August 2006 and October 2009.
  
  
  METHODS
  Sequential analyses were conducted weekly to detect associations between HPV4 exposure and pre-specified outcomes. The pre-specified outcomes identified by ICD-9 codes using computerized data at the participating MCOs included: Guillan-Barré Syndrome (GBS), stroke, venous thromboembolism (VTE), appendicitis, seizures, syncope, allergic reactions, and anaphylaxis. For rare outcomes, historical background rates were used as the comparison group. For more common outcomes, a concurrent unexposed comparison group was utilized. A standardized review of medical records was conducted for all cases of GBS, VTE, and anaphylaxis.
  
  
  RESULTS
  A total of 600,558 HPV4 doses were administered during the study period. We found no statistically significant increased risk for the outcomes studied. However, a non-statistically significant relative risk (RR) for VTE ICD-9 codes following HPV4 vaccination of 1.98 was detected among females age 9-17 years. Medical record review of all 8 vaccinated potential VTE cases in this age group revealed that 5 met the standard case definition for VTE. All 5 confirmed cases had known risk factors for VTE (oral contraceptive use, coagulation disorders, smoking, obesity or prolonged hospitalization).
  
  
  CONCLUSIONS
  In a study of over 600,000 HPV4 vaccine doses administered, no statistically significant increased risk for any of the pre-specified adverse events after vaccination was detected. Further study of a possible association with VTE following HPV4 vaccination is warranted.
authors: Division of Healthcare Quality and Promotion, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. jgee@cdc.gov
authors: Julianne
authors: J
authors: Gee
authors: Allison
authors: A
authors: Naleway
authors: Irene
authors: I
authors: Shui
authors: James
authors: J
authors: Baggs
authors: Ruihua
authors: R
authors: Yin
authors: Rong
authors: R
authors: Li
authors: Martin
authors: M
authors: Kulldorff
authors: Edwin
authors: E
authors: Lewis
authors: Bruce
authors: B
authors: Fireman
authors: Matthew F
authors: MF
authors: Daley
authors: Nicola P
authors: NP
authors: Klein
authors: Eric S
authors: ES
authors: Weintraub
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D002648:Child; D015331:Cohort Studies; D016208:Databases, Factual; D005260:Female; D006801:Humans; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects*; D011358:Product Surveillance, Postmarketing; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D053918:Papillomavirus Vaccines