Tina Hovgaard Lützen, Bodil Hammer Bech, Jesper Mehlsen, Claus Høstrup Vestergaard, Lene Wulff Krogsgaard, Jørn Olsen, Mogens Vestergaard, Oleguer Plana-Ripoll, Dorte Rytter

No association between human papilloma virus (HPV) vaccination and numerous diseases has been found. Still, a large number of Danish women are reporting suspected adverse events. Other factors may play a role, and the aim of this study is to examine the association between psychiatric conditions, general practitioner (GP) attendance and indicators of psychological symptoms prior to HPV vaccination and the risk of referral to an HPV center following vaccination. Register-based, matched case-control study. Cases were identified from five Danish, regional HPV centers, and health data for cases and controls were obtained from national registries. Cases were defined as women referred to an HPV center between January 1, 2015 and December 31, 2015 (n=1,496). Each case was matched with five controls on age, region and time of first vaccine registration. The total study population consisted of 8,976 women. Overall, women above 18 years who had been referred to an HPV center were more likely to have used psychiatric medication (odds ratio [OR]: 1.88 [95% CI 1.48-2.40]) or to have been hospitalized because of a psychiatric disorder within 5 years prior to the first vaccine registration (OR: 2.13 [95% CI 1.59-2.86]). Specifically, referred women were more likely to have used antipsychotics, antidepressants, attention deficit hyperactivity disorder (ADHD) medication or anxiolytics, and to have been hospitalized for affective disorders or anxiety, but not to have been hospitalized for schizoid, ADHD or eating disorders. In addition, they were more likely to have had talk therapy or psychometric test performed prior to vaccination (OR: 1.72 [95% CI 0.1.35-2.18] and OR: 1.67 [95% CI 1.30-2.13], respectively). Referred women of all ages had higher use of GP before vaccination. Population attributable fraction analyses indicated that psychiatric medication, hospitalization due to a psychiatric disorder and use of talk therapy, or psychometric test "explained" 13%, 10%, 12% and 11% of the referrals, respectively. Results did not change substantially when adjusted for potential confounders. Women referred to HPV centers because of suspected adverse events after vaccination more often had preexisting psychiatric conditions, psychological symptoms or frequent GP attendance prior to HPV vaccination.