No association of complex regional pain syndrome and other neurological disorders with human papillomavirus vaccination in a large-scale real-world database

Establishing evidence of vaccine safety is critical for optimizing vaccine coverage. This study aimed to assess the risk of developing neurological disorders following human papillomavirus (HPV) vaccination. This retrospective cohort study compared the risk of developing neurological disorders between HPV-vaccinated and unvaccinated cohorts using the TriNetX platform. Outcomes included complex regional pain syndrome (CRPS), postural orthostatic tachycardia syndrome (POTS), polyneuropathies, dysautonomia, Guillain-Barré syndrome (GBS), encephalitis, myelitis or optic neuritis, Bell's palsy, epilepsy, narcolepsy, and intracranial injury (negative control outcome). The hazard ratios (HRs) were estimated by propensity score matching. In the US, following propensity score matching, 715,540 participants from each cohort were matched. The HRs were 0.58 [0.47-0.73] for CRPS; 0.78 [0.69-0.87] for POTS; 0.60 [0.53-0.69] for polyneuropathies; 0.67 [0.62-0.73] for dysautonomia; 0.69 [0.38-1.26] for GBS; 0.62 [0.50-0.77] for encephalitis, myelitis or optic neuritis; 1.00 [0.87-1.15] for Bell's palsy; 0.67 [0.63-0.71] for epilepsy; 0.67 [0.63-0.71] for narcolepsy; and1.02 [0.99-1.04] for intracranial injury. No increased risk of the selected neurological adverse events was observed in the vaccinated group. The data should be interpreted with caution given potential residual confounders. This study contributes to the establishment of evidence for the safety of HPV vaccines.