title: Absence of venous thromboembolism risk following quadrivalent human papillomavirus vaccination, Vaccine Safety Datalink, 2008-2011.
abstract: BACKGROUND
  To investigate concerns about a potential association between quadrivalent human papillomavirus vaccination (HPV4) and venous thromboembolism (VTE), we conducted a self-controlled case series study in adolescents and young adults 9-26 years of age in the Vaccine Safety Datalink.
  
  
  METHODS
  We identified potential VTE cases diagnosed in 2008 through 2011 who had also received at least one HPV4 dose during that period. We confirmed each presumptive diagnosis by medical record review. We calculated incidence rate ratios (IRRs) and 95% confidence intervals (CI) to estimate the risk in the 1-60 day period following HPV4 exposure and in subsets of that period. IRRs were stratified by age, gender, hormonal contraceptive use, and recent surgery or trauma.
  
  
  RESULTS
  We identified 313 potential cases of VTE among HPV4 vaccinees, and 291 (93%) had sufficient medical records for review. Of these, we confirmed 156 (54%) cases. VTE was uncommon among males (n=3) and 9-12 year olds (n=4). Nearly all confirmed cases (97%) had at least one known risk factor for VTE, including hormonal contraceptive use, obesity, and hypercoagulability. Sixteen (10%) confirmed cases occurred in the 1-60 days following HPV4 exposure. The risk of VTE varied from 1.47 (95% CI: 0.47-4.64) in the 1-7 days following HPV4 exposure to 0.92 (95% CI: 0.54-1.57) in the 1-60 days following vaccination. It was not possible to calculate a stratified IRR for males due to small sample size; the other risk factors evaluated did not significantly affect the risk of VTE after HPV4 exposure.
  
  
  CONCLUSIONS
  The risk of developing VTE among 9- to 26-year-olds was not elevated following HPV4 exposure. Sample size limited our ability to rigorously evaluate potential effect modifiers, such as gender, through stratified analysis.
authors.affiliation: Center for Health Research, Kaiser Permanente Northwest, Portland, OR, USA. Electronic address: allison.naleway@kpchr.org.
authors.forename: Allison L
authors.initials: AL
authors.lastname: Naleway
authors.affiliation: Center for Health Research, Kaiser Permanente Northwest, Portland, OR, USA.
authors.forename: Brad
authors.initials: B
authors.lastname: Crane
authors.affiliation: Center for Health Research, Kaiser Permanente Northwest, Portland, OR, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Smith
authors.affiliation: Institute for Health Research, Kaiser Permanente Colorado, Denver, CO, USA.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Daley
authors.affiliation: Marshfield Clinic Research Foundation, Marshfield, WI, USA.
authors.forename: James
authors.initials: J
authors.lastname: Donahue
authors.affiliation: Immunization Safety Office, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Julianne
authors.initials: J
authors.lastname: Gee
authors.affiliation: Harvard Pilgrim Health Care Institute and Department of Population Medicine, Harvard Medical School, Boston, MA, USA.
authors.forename: Sharon K
authors.initials: SK
authors.lastname: Greene
authors.affiliation: Immunization Safety Office, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Theresa
authors.initials: T
authors.lastname: Harrington
authors.affiliation: Group Health Research Institute, Seattle, WA, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Jackson
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
authors.forename: Nicola P
authors.initials: NP
authors.lastname: Klein
authors.affiliation: Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA.
authors.forename: Hung Fu
authors.initials: HF
authors.lastname: Tseng
authors.affiliation: Immunization Safety Office, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Vellozzi
authors.affiliation: Immunization Safety Office, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Weintraub
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D015331:Cohort Studies; 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; D015994:Incidence; D008297:Male; D030361:Papillomavirus Infections / Q000517:prevention & control; D018570:Risk Assessment; D054556:Venous Thromboembolism / Q000139:chemically induced* / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18
keywords: Adolescents; Human papillomavirus vaccine; Safety; Venous thromboembolism