Elevated C-reactive Protein Levels and Malignant Transformation Risk in Patients With Oral Mucosal Diseases

Abstract

Introduction and aims: Chronic inflammation is recognised as a hallmark of cancers. This multicentre cohort study investigated the influence of elevated serum C-reactive protein (CRP) levels on the malignant transformation risk of oral inflammatory diseases and lesions with malignant potential utilising the Observational Medical Outcomes Partnership Common Data Model. Methods: This retrospective, observational cohort study included the data from 9 medical centres. CRP levels recorded within 30 days of oral diseases diagnosis were analysed. A meta-regression identified 0.269 mg/dL as the optimal threshold for predicting malignancy. Patients were classified into elevated CRP (CRP >= 0.269 mg/dL) and control (CRP <0.269 mg/dL) groups. Cox proportional hazard models were applied to estimate risk of developing oral squamous cell carcinoma (OSCC), followed by 1:1 and 1:2 propensity score matching and pooled meta-analyses. Results: In total, 10029 individuals with oral diseases and available CRP data were included, comprising 4142 and 5887 in the elevated CRP and control groups, respectively. Overall, 204 individuals (2.03%) progressed to OSCC, with higher incidence in the elevated CRP group (2.32%) compared with controls (1.83%). Elevated CRP was significantly associated with increased OSCC risk in both 1:1 (HR = 1.79 [95% CI 1.08-2.95]), and 1:2 propensity score matching models (HR = 1.55 [95% CI 1.01-2.38]). Conclusions: Elevated CRP levels, indicative of systemic inflammation, were linked to an increased risk of malignant progression in patients with inflammatory oral conditions and lesions with malignant potential. Understanding the role of inflammation may help assess OSCC risk and improve prevention. (c) 2026 The Authors. Published by Elsevier Inc. on behalf of FDI World Dental Federation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)