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A digital score of peri‐epithelial lymphocytic activity predicts malignant transformation in oral epithelial dysplasia

2023/06/09 by Raja Muhammad Saad Bashir, Adam Shephard, Adam J Shephard +6 · 33 citations
Computer Science · Dentistry · Medicine · #AI in cancer detection #Basal (medicine) #Basal cell #Biology #Dysplasia #Epithelial dysplasia #Epithelium #Gastroenterology #Histology #Internal medicine #Malignant transformation #Medicine #Oral Health Pathology and Treatment #Oral and Maxillofacial Pathology #Pathology #Stage (stratigraphy)

paper · pdf · doi:10.1002/path.6094

published in The Journal of Pathology 260(4), 431-442

openalex publication_date 2023/06/09 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28

Abstract

Oral squamous cell carcinoma (OSCC) is amongst the most common cancers, with more than 377,000 new cases worldwide each year. OSCC prognosis remains poor, related to cancer presentation at a late stage, indicating the need for early detection to improve patient prognosis. OSCC is often preceded by a premalignant state known as oral epithelial dysplasia (OED), which is diagnosed and graded using subjective histological criteria leading to variability and prognostic unreliability. In this work, we propose a deep learning approach for the development of prognostic models for malignant transformation and their association with clinical outcomes in histology whole slide images (WSIs) of OED tissue sections. We train a weakly supervised method on OED cases (n = 137) with malignant transformation (n = 50) and mean malignant transformation time of 6.51 years (±5.35 SD). Stratified five-fold cross-validation achieved an average area under the receiver-operator characteristic curve (AUROC) of 0.78 for predicting malignant transformation in OED. Hotspot analysis revealed various features of nuclei in the epithelium and peri-epithelial tissue to be significant prognostic factors for malignant transformation, including the count of peri-epithelial lymphocytes (PELs) (p < 0.05), epithelial layer nuclei count (NC) (p < 0.05), and basal layer NC (p < 0.05). Progression-free survival (PFS) using the epithelial layer NC (p < 0.05, C-index = 0.73), basal layer NC (p < 0.05, C-index = 0.70), and PELs count (p < 0.05, C-index = 0.73) all showed association of these features with a high risk of malignant transformation in our univariate analysis. Our work shows the application of deep learning for the prognostication and prediction of PFS of OED for the first time and offers potential to aid patient management. Further evaluation and testing on multi-centre data is required for validation and translation to clinical practice. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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