| Phase III clinical trials and post-licensure surveillance have demonstrated the safety and efficacy of human papillomavirus (HPV) vaccines. The U.S. Advisory Committee on Immunization Practices recommends universal HPV vaccination at age 11--12, alongside tetanus-diphtheria-acellular pertussis (Tdap) and meningococcal conjugate (MenACWY) vaccination.;Despite this recommendation, adolescents initiate HPV vaccination less frequently than Tdap and MenACWY vaccination, due partially to concerns about HPV vaccine safety. Reports of complex regional pain syndrome (CRPS) following HPV vaccination in Japan may have exacerbated safety concerns regarding HPV vaccination. To date, however, no epidemiological research has linked HPV vaccination to CRPS. We analyzed private U.S. insurance claims between 2006--2014 to assess 1) patterns of use of HPV vaccination compared to Tdap and MenACWY among adolescents; and 2) the hazard of CRPS following HPV vaccination compared to Tdap and MenACWY among girls.;Among 1,691,223 adolescents, HPV vaccination occurred later than Tdap or MenACWY vaccination. Half of vaccinated adolescents received Tdap and MenACWY vaccination only; however, co-administration of all three vaccines increased with birth cohort. Rural adolescents were less likely than urban adolescents to receive each vaccination except in the Northeast, where they were more likely to receive HPV vaccination (incidence rate ratio: 1.09, 95% CI: 1.05, 1.13). Timely HPV vaccination was associated with female sex, urbanicity, Western residence, and later birth cohort.;We identified 563 CRPS cases among 1,232,572 girls. CRPS hazard was not significantly elevated following recent HPV, Tdap, or MenACWY vaccination. Ever receiving Tdap and MenACWY vaccination were associated with CRPS in crude analysis, but were not associated after adjusting for trauma. Concomitant administration of HPV vaccine with other adolescent vaccines conferred no excess hazard of CRPS. Girls with lower limb injuries had the greatest CRPS hazard compared to girls without (HR: 12.4, 95% CI: 10.4, 14.7), and common pediatric illnesses (e.g. asthma, respiratory infections, allergies) were positively associated with CRPS.;HPV vaccination remains suboptimal among U.S. adolescents. We observed no vaccine safety signals with respect to CRPS, supporting current adolescent vaccination recommendations. Health care providers should strongly recommend timely HPV vaccination with other recommended adolescent vaccines to provide optimal protection against HPV-associated cancers. |
