Development and validation of a multivariable model for prediction of malignant transformation and recurrence of oral epithelial dysplasia

Hanya Mahmood*, Adam Shephard, Paul Hankinson, Mike Bradburn, Anna Luiza Damaceno Araujo, Alan Roger Santos-Silva, Marcio Ajudarte Lopes, Pablo Agustin Vargas, Kris D. McCombe, Stephanie G. Craig, Jacqueline James, Jill Brooks, Paul Nankivell, Hisham Mehanna, Nasir Rajpoot, Syed Ali Khurram

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
22 Downloads (Pure)

Abstract

Background
Oral epithelial dysplasia (OED) is the precursor to oral squamous cell carcinoma which is amongst the top ten cancers worldwide. Prognostic significance of conventional histological features in OED is not well established. Many additional histological abnormalities are seen in OED, but are insufficiently investigated, and have not been correlated to clinical outcomes.

Methods
A digital quantitative analysis of epithelial cellularity, nuclear geometry, cytoplasm staining intensity and epithelial architecture/thickness is conducted on 75 OED whole-slide images (252 regions of interest) with feature-specific comparisons between grades and against non-dysplastic/control cases. Multivariable models were developed to evaluate prediction of OED recurrence and malignant transformation. The best performing models were externally validated on unseen cases pooled from four different centres (n = 121), of which 32% progressed to cancer, with an average transformation time of 45 months.

Results
Grade-based differences were seen for cytoplasmic eosin, nuclear eccentricity, and circularity in basal epithelial cells of OED (p < 0.05). Nucleus circularity was associated with OED recurrence (p = 0.018) and epithelial perimeter associated with malignant transformation (p = 0.03). The developed model demonstrated superior predictive potential for malignant transformation (AUROC 0.77) and OED recurrence (AUROC 0.74) as compared with conventional WHO grading (AUROC 0.68 and 0.71, respectively). External validation supported the prognostic strength of this model.

Conclusions
This study supports a novel prognostic model which outperforms existing grading systems. Further studies are warranted to evaluate its significance for OED prognostication.

Original languageEnglish
Pages (from-to)1599-1607
Number of pages9
JournalBritish Journal of Cancer
Volume129
Issue number10
Early online date27 Sept 2023
DOIs
Publication statusPublished - 09 Nov 2023

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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