Evaluation of the Risk of Inflammatory Bowel Disease after the HPV Vaccination in Primary Care in Spain: A Time-Varying Cohort Analysis of Around 390,000 Girls

Drug Saf. 2021 Apr;44(4):455-466. doi: 10.1007/s40264-020-01040-0. Epub 2021 Jan 19.

Abstract

Introduction: A link between the human papillomavirus vaccination (HPVv) and inflammatory bowel disease (IBD) has been suggested.

Objective: We aimed to estimate the risk of IBD following HPVv compared with periods not exposed to the vaccines.

Methods: Primary healthcare records (Spanish Primary Care Database For Pharmacoepidemiological Research [BIFAP]) were used in a cohort study of girls in Spain aged 9-18 years between 2007 and 2016 free of IBD or HPVv at study entrance. During the follow-up to IBD diagnosis, time-varying HPVv exposure and confounders were assessed in Cox models to estimate the hazard ratio (HRs) of IBD in the 2 years after HPVv (exposed period) and thereafter (post-exposed) compared with the no exposure periods. In a post hoc analysis, we moved the IBD date back 30 days as a theoretical delay in diagnosis confirmation.

Results: The cohort comprised 388,669 girls; 154,174 of these received the HPVv, and 88 IBD cases occurred (55 non-exposed, 22 exposed [after first N = 6, second N = 2, or third N = 14 dose] and 11 in post-exposed periods). The adjusted HR was 1.66 (95% confidence interval [CI] 0.68-4.05) for exposed and 1.10 (95% CI 0.37-3.24) for post-exposed periods. The HR for the first dose was 3.94 (95% CI 1.19-13.02). No association was found for the second or third doses. Post hoc, the HR was 1.83 (95% CI 0.72-4.69) for exposed periods (N = 18), and 1.84 (95% CI 0.35-9.83; N = 2), 1.50 (95% CI 0.40-5.63; N = 4) and 1.98 (95% CI 0.71-5.49; N = 12) after the first, second and third doses, respectively.

Conclusions: This study did not show an increased risk of IBD following 2 years of HPVv exposure. However, an increased risk of IBD diagnosis was observed following the first vaccination dose (1-34 days), which is likely attributable to the clinical recommendation to vaccinate upon onset of IBD symptoms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chronic Disease
  • Cohort Studies
  • Female
  • Humans
  • Inflammatory Bowel Diseases* / epidemiology
  • Inflammatory Bowel Diseases* / etiology
  • Male
  • Papillomavirus Infections* / epidemiology
  • Papillomavirus Infections* / prevention & control
  • Papillomavirus Vaccines* / adverse effects
  • Primary Health Care
  • Spain / epidemiology
  • Vaccination / adverse effects

Substances

  • Papillomavirus Vaccines