Infectious disease hospitalization rates before and after introduction of vaccine against human papillomavirus in Denmark, Norway, and Sweden: controlled interrupted time series analyses

BACKGROUND: It has been suggested that non-live vaccines may increase the risk of non-targeted infections, especially in girls. We examined whether the introduction of non-live human papillomavirus (HPV) vaccine was associated with an increased rate of infectious disease hospitalization among girls in Denmark, Norway, and Sweden. METHODS: Using data from national patient registries, we performed controlled interrupted time series analyses including an intervention group (13-year-old girls in Denmark, 8th-grade girls in Norway, 7th grade girls in Sweden) and a control group not offered HPV vaccine (boys of the same age/grade). Infectious disease hospitalization rates were modelled using negative binomial regression, and the level change, i.e. the incidence rate ratio corresponding to the relative change to the rate's underlying trend following introduction of HPV vaccine, was estimated. RESULTS: For infectious disease hospitalizations of any duration, the level change among girls and boys, respectively, was 1.21 (95% confidence interval (CI) 0.94-1.57) and 0.73 (95% CI 0.56-0.96) in Denmark; 1.21 (95% CI 0.94-1.56) and 1.14 (95% CI 0.88-1.49) in Norway; and 0.83 (95% CI 0.65-1.07) and 0.72 (95% CI 0.56-0.92) in Sweden. For hospitalizations with ≥2 overnight stays, the level change was 1.05 (95% CI 0.71-1.56) and 0.81 (95% CI 0.54-1.20) among Danish girls and boys, respectively, whereas the results in Norway and Sweden were similar to the results for hospitalizations of any duration. CONCLUSION: Changes to the rate following introduction of HPV vaccine were similar among girls and boys in Norway and Sweden, in line with there being no association between HPV vaccination and infectious disease hospitalizations. The difference between Danish girls and boys seems unlikely to be attributable to HPV vaccine, given the Norwegian and Swedish results. Overall, our study does not support that HPV vaccination increases risk of infectious disease hospitalization.