Hospital contacts and diagnoses five years prior to HPV vaccination among females referred for suspected adverse vaccine effects: A Danish nationwide case-control study

Vaccine. 2019 Mar 22;37(13):1763-1768. doi: 10.1016/j.vaccine.2019.02.029. Epub 2019 Feb 23.


Background: High health care utilization before Human Papilloma Virus (HPV) vaccination might be associated with increased risk of suspected adverse effects (AE's) after vaccination. We investigated the association between hospital contacts and diagnoses before HPV vaccination and risk of later referral to a specialized hospital setting (HPV center) for suspected AE's.

Methods: The study was a Danish register-based matched case-control study. Cases were females referred to an HPV center. Five controls per case were randomly selected in the source population of HPV vaccinated females. Information on hospital contacts and diagnoses was obtained from the Danish National Patient Registry. Conditional logistic regression analyses were used to investigate the association between having one or more diagnoses in each specific International Classification of Diseases 10th version (ICD-10) chapter five years before the HPV vaccination and subsequent referral to an HPV center.

Results: We identified 1496 cases and 7480 controls. In total, 80% of the cases versus 65% of the controls had at least one hospital contact prior to HPV vaccination (Prevalence Proportion Ratio - PPR: 1.24 (95% Confidence Interval - CI: 1.21-1.27)), with 24% vs 12% (PPR: 1.97 (95% CI: 1.76-2.19)) having six or more contacts. Cases were more likely to have had a diagnosis in 15 out of 19 ICD-10 chapters before the vaccination, with ORs larger than 1.8 for infectious diseases, psychiatric diseases, diseases of the nervous, circulatory, digestive and musculoskeletal system, unspecific symptoms and unspecific contacts.

Conclusion: Pre-vaccination morbidity and health care utilization seem to play a role in the path leading to suspected AE's after HPV vaccination. Since many of the diagnoses that were particularly increased before vaccination in referred females are overlapping with the most frequent symptoms reported, we cannot exclude that for some of the females, the suspected AE's might have been existing already before the vaccination.

Keywords: Diagnoses; HPV vaccine; Hospital contacts; Matched case-control study; Register based; Suspected adverse effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Child
  • Denmark / epidemiology
  • Female
  • Hospitals
  • Humans
  • Middle Aged
  • Odds Ratio
  • Papillomaviridae / immunology*
  • Papillomavirus Infections / diagnosis
  • Papillomavirus Infections / epidemiology*
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Vaccines / administration & dosage
  • Papillomavirus Vaccines / immunology*
  • Patient Acceptance of Health Care
  • Public Health Surveillance
  • Vaccination*
  • Young Adult


  • Papillomavirus Vaccines