Hazard of complex regional pain syndrome following human papillomavirus vaccination among adolescent girls in the United States: a case-cohort analysis of insurance claims data.

Objectives: Complex regional pain syndrome (CRPS) cases have followed human papillomavirus (HPV) vaccination, but no causal link has been established.Methods: Using insurance claims, the authors observed unvaccinated 11-year-old girls for CRPS diagnoses. The authors used time-dependent Cox regression to identify health-related CRPS predictors using diagnosis codes. Next, the authors identified HPV vaccinations using procedural codes. HPV vaccination and CRPS predictors were considered time-dependent covariates to estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) for CRPS, 30, 90, and 180-days post-vaccination.Results: 1,232,572 girls received 563 unique CRPS diagnoses. In a 10% sub-cohort of 123,981 girls accounting for potential confounders and predisposing risk factors (i.e. injury, infection, mental illness, primary care use), CRPS hazard was not significantly elevated 30 days (HR: 0.90, 95% CI: 0.46, 1.73), 90 days (HR: 1.17, 95% CI: 0.83, 1.65), or 180-days post-vaccination (HR: 1.11, 95% CI: 0.83, 1.47).Conclusion: The results support the safety and continued administration of HPV vaccines to adolescents.