ArticleHead and neck pathology2026
Integrated Clinical, Histopathological, and Inflammatory Parameters for Predicting Malignant Transformation in High-Risk Oral Potentially Malignant Disorders: A Prospective Study.
Article in Head and neck pathology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundOral epithelial dysplasia (OED) is a recognised precursor of oral squamous cell carcinoma (OSCC). Previous studies have identified specific OED features that are significantly associated with recurrence and malignant transformation (MT) in oral leukoplakia (OL). However, these findings lack validation and have not been comprehensively evaluated in well-designed prospective cohorts.
methodsIn this prospective study of 449 human papillomavirus-negative OPMD patients (median follow-up: 41.2 months), clinico-demographic, histopathological, and systemic inflammatory parameters were analysed to identify predictors of persistence, recurrence, and MT. Hematoxylin and eosin-stained slides were independently reviewed by two pathologists, with discrepancies resolved by consensus. Associations were assessed using chi-square tests, ordinal logistic regression, Kaplan–Meier survival analysis and Cox proportional hazards regression. Variable importance was determined using mean decrease in Gini (MDG) scores derived from a random forest (RF) algorithm. Model performance was evaluated using the area under the receiver operating characteristic (AUROC) curve.
resultsIncreasing age and lesion site were significantly associated with adverse outcomes (recurrence and/or MT). Tobacco exposure quantified as cigarette pack-years (p = 0.012) and bidi pack-years (p < 0.001), as well as combined tobacco chewing, smoking and alcohol consumption (p = 0.025), were significantly associated with clinical risk. A lower platelet-to-lymphocyte ratio was also significantly associated with adverse outcomes (p = 0.031). Histopathologically, OED grade (p = 0.004) and increasing severity (mild, moderate and severe) were associated with shorter time to MT (p < 0.001). RF analysis identified irregular epithelial stratification (MDG = 52.2) and enlarged nucleoli (MDG = 38.6) as the strongest predictors of MT. The OED-only model achieved an AUROC of 0.75 (sensitivity 72.7%, specificity 63.4%), improving to 0.77 (sensitivity 90.9%, specificity 55.3%) after inclusion of age and smoking variables.
conclusionThis study underscores the importance of OED features in combination with clinical and inflammatory parameters. Validation in multi-centric cohorts with higher recurrence and MT rates is warranted to confirm their clinical utility.
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