Abstract
BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare autoimmune disease characterized by small- and medium-vessel inflammation. Although chronic immune dysregulation and cytotoxic therapy exposure have been hypothesized to increase malignancy risk, large-scale, real-world evidence quantifying these risks has been limited. This study aimed to characterize hematologic and solid-organ malignancy risk profiles in patients with AAV using a large, multi-institutional database. METHODS: We conducted a retrospective cohort study using the TriNetX Research Network, using de-identified electronic medical record data from 2014 to 2024. We identified 19,238 patients with AAV and performed 1:1 propensity score matching to seborrheic keratosis controls on demographic and clinical covariates, yielding 18,255 matched pairs. Five-year incidences of hematologic and solid-organ malignancies were compared using hazard ratios (HR) and 95% confidence intervals (95% CI) from Cox proportional hazards regressions. RESULTS: Here we show that patients with AAV have a significantly increased risk of overall cancer (HR 1.23; 95% CI 1.12-1.35), driven by higher rates of hematologic malignancies (HR 2.12; 95% CI 1.77-2.53) and specific solid-organ cancers including lung (HR 1.78), bladder (HR 1.99), brain (HR 2.22), and lip/oral cavity/pharyngeal cancers (HR 1.78). Myelodysplastic syndromes (HR 4.11) and leukemia (HR 2.72) show the strongest associations. Negative controls show no risk elevation. CONCLUSIONS: Patients with AAV face distinct and heightened risks for select hematologic and solid-organ malignancies, supporting the need for tailored cancer surveillance strategies. These findings provide a large-scale, real-world evidence base for malignancy risk stratification and proactive screening in AAV.