Infectious disease hospitalization after receipt of human papillomavirus vaccine: a nationwide register-based cohort study among Danish, Finnish, Norwegian, and Swedish girls

It has been suggested that non-live vaccines may increase susceptibility to non-targeted infections and that such deleterious non-specific effects are more pronounced in girls. We investigated whether receipt of non-live vaccine against human papillomavirus (HPV) was associated with increased risk of infectious disease hospitalization. A nationwide cohort study based on detailed individual-level data from national registries was performed in Denmark, Finland, Norway, and Sweden. The cohort consisted of girls aged 11–14 years in Denmark, Finland, and Norway, and 10–14 years in Sweden. Cox regression, with extensive control for potential confounders, was used to assess whether risk of infectious disease hospitalization with at least one overnight stay differed according to time-varying HPV vaccination status. In total, 754 458 girls were included in the analysis. The infectious disease hospitalization rate (per 10 000 person years) was 44.1 in Denmark, 35.7 in Finland, 37.1 in Norway, and 28.5 in Sweden. Comparing HPV-vaccinated with HPV-unvaccinated person time, the adjusted hazard ratio (95% confidence interval) was 0.81 (0.72, 0.90) in Denmark, 0.69 (0.60, 0.80) in Finland, 0.76 (0.66, 0.88) in Norway, and 0.59 (0.49, 0.71) in Sweden. Decreased risk was observed regardless of number of doses, except in Norway, where risk among girls with only one dose did not differ from risk among unvaccinated girls. Receipt of HPV vaccine was consistently associated with decreased risk of infectious disease hospitalization among girls in the Nordic countries. Our study does not support that HPV vaccines have deleterious non-specific effects.