Assessing the Risk of Autoimmune Diseases Following Human Papillomavirus Vaccination: A Systematic Review

Abstract

Background: Human papillomavirus (HPV) vaccination is an effective strategy for preventing HPV-related cancers and infections. Concerns about a possible association between HPV vaccination and autoimmune diseases remain controversial. The aim of this systematic review was to evaluate the current evidence on the relationship between HPV vaccination and the risk of new-onset autoimmune diseases. Methods: A systematic search of PubMed and Embase was conducted in April 2026. Eligible studies assessed autoimmune outcomes following HPV vaccination in humans and included randomized controlled trials, cohort studies, case-control studies, self-controlled case series, cross-sectional studies, and pharmacovigilance analyses. Reviews, case reports, editorials, and animal studies were excluded. The review followed PRISMA 2020 guidelines. Due to methodological heterogeneity, findings were synthesized narratively. Results: Of 530 identified records, 29 studies met the inclusion criteria. Evidence from randomized trials, large cohort studies, and other observational designs involving millions of vaccinated individuals showed no consistent increase in the risk of autoimmune diseases after HPV vaccination. Most studies reported no association with Guillain–Barré syndrome, multiple sclerosis, type 1 diabetes, autoimmune thyroid diseases, inflammatory bowel disease, connective tissue disorders, or other immune-mediated conditions. Although a few studies reported significant associations, these findings were not consistently replicated. Conclusions: Current evidence does not support a consistent association between HPV vaccination and new-onset autoimmune diseases. Available data indicate a favorable safety profile, while continued surveillance remains important for detecting rare adverse events.