Human papillomavirus vaccination of adult women and risk of autoimmune and neurological diseases

J Intern Med. 2018 Feb;283(2):154-165. doi: 10.1111/joim.12694. Epub 2017 Oct 18.


Background: Since 2006, human papillomavirus (HPV) vaccines have been introduced in many countries worldwide. Whilst safety studies have been reassuring, focus has been on the primary target group, the young adolescent girls. However, it is also important to evaluate safety in adult women where background disease rates and safety issues could differ significantly.

Objective: We took advantage of the unique Danish and Swedish nationwide healthcare registers to conduct a cohort study comparing incidence rate ratios (RRs) of 45 preselected serious chronic diseases in quadrivalent HPV (qHPV)-vaccinated and qHPV-unvaccinated adult women 18-44 years of age.

Methods: We used Poisson regression to estimate RRs according to qHPV vaccination status with two-sided 95% confidence intervals (95% CIs).

Results: The study cohort comprised 3 126 790 women (1 195 865 [38%] Danish and 1 930 925 [62%] Swedish) followed for 16 386 459 person-years. Vaccine uptake of at least one dose of qHPV vaccine was 8% in the cohort: 18% amongst Danish women and 2% amongst Swedish. We identified seven adverse events with statistically significant increased risks following vaccination-Hashimoto's thyroiditis, coeliac disease, localized lupus erythematosus, pemphigus vulgaris, Addison's disease, Raynaud's disease and other encephalitis, myelitis or encephalomyelitis. After taking multiple testing into account and conducting self-controlled case series analyses, coeliac disease (RR 1.56 [95% confidence interval 1.29-1.89]) was the only remaining association.

Conclusion: Unmasking of conditions at vaccination visits is a plausible explanation for the increased risk associated with qHPV in this study because coeliac disease is underdiagnosed in Scandinavian populations. In conclusion, our study of serious adverse event rates in qHPV-vaccinated and qHPV-unvaccinated adult women 18-44 years of age did not raise any safety issues of concern.

Keywords: Cohort study; Epidemiology; Human papillomavirus; Vaccine Safety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Autoimmune Diseases / epidemiology
  • Autoimmune Diseases / etiology*
  • Cohort Studies
  • Denmark / epidemiology
  • Female
  • Humans
  • Mass Vaccination / adverse effects*
  • Nervous System Diseases / epidemiology
  • Nervous System Diseases / etiology*
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Vaccines / administration & dosage
  • Papillomavirus Vaccines / adverse effects*
  • Registries
  • Risk Factors
  • Sweden / epidemiology
  • Young Adult


  • Papillomavirus Vaccines