Risk of Juvenile Idiopathic Arthritis Following HPV9 Vaccination: A Retrospective Cohort Study Before and During the COVID-19 Pandemic

Objective

To evaluate whether 9-valent human papillomavirus (HPV9) vaccination is associated with an increased risk of juvenile idiopathic arthritis (JIA), particularly during the coronavirus disease-2019 (COVID-19) pandemic.

Patients and Methods

We conducted a retrospective cohort study using TriNetX U.S. Collaborative Network data from January 1, 2016, to December 31, 2023. Girls aged 9-13 years who received their first HPV9 dose in either the prepandemic (2016-2019) or pandemic (2020-2023) period were matched with unvaccinated controls. Exclusion criteria included previous JIA diagnosis, antirheumatic drug use, or positive rheumatoid factor. Incidence of new-onset JIA was tracked over 8 days to 36 months. Cox regression and Kaplan-Meier survival analysis were used to evaluate hazard ratios (HRs) and JIA-free survival.

Results

Among 99,243 vaccinated and 1.1 million control individuals, HPV9 recipients had a significantly reduced risk of JIA at 36 months in both periods (HR 2016-2019, 0.207, P<.001; HR 2020-2023, 0.287, P<.001). No increased risk was observed during the early postvaccination period. The estimated cumulative probability of JIA did not differ significantly between vaccinated groups across the 2 periods (P=.9), nor among unvaccinated controls (P=.238), indicating no modifying effect from COVID-19.

Conclusion

The HPV9 vaccination was associated with a lower risk of JIA, and this effect can last at least for 3 years. The COVID-19 pandemic did not alter this relationship. These findings reinforce the immunological safety of HPV9 and provide reassurance for adolescent vaccination programs, even in pandemic contexts.