{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T19:53:09Z","timestamp":1788292389851,"version":"build-2803163510"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Human papillomavirus (HPV) infection has been implicated in autoimmune processes, yet concerns remain about the potential autoimmune risks of HPV vaccination. Juvenile idiopathic arthritis (JIA) is a chronic autoimmune condition that typically manifests in childhood. The relationship between HPV vaccination and the development of JIA remains uncertain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a retrospective cohort study using data from the TriNetX U.S. Collaborative Network. Females aged 9\u201313 years were included. Three analyses were performed: (1) comparing HPV4-vaccinated vs. unvaccinated matched cohorts; (2) a stricter comparison excluding subjects with positive ANA; (3) comparing single vs. multiple HPV4 doses. Propensity score matching and Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In Analysis 1 (n=55,257 pairs) and Analysis 2 (n=53,827 pairs), the HPV4-vaccinated groups showed significantly reduced rates of JIA from 12 to 36 months post-vaccination (HR range: 0.33\u20130.52). No difference in JIA risk was observed between single and multiple doses in Analysis 3 (n=20,822 pairs). Early-onset JIA (&amp;lt;6 months after HPV4 vaccine) showed inconsistent trends, with only limited protective signals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings suggest that HPV4 vaccination is not associated with an increased risk of JIA. On the contrary, vaccination may confer a long-term protective effect against new-onset JIA, observable from 6\u201312 months and lasting for at least 3 years. These findings support the safety and possible immunoregulatory benefit of HPV4 in adolescents.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1621939","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T05:26:50Z","timestamp":1756099610000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Risk of developing juvenile idiopathic arthritis after quadrivalent HPV vaccination: a retrospective cohort study using the TriNetX U.S. 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