Abnormal DNA content in oral epithelial dysplasia is associated with increased risk of progression to carcinoma

TLDR

Oral epithelial dysplasia can progress to carcinoma, yet reliable predictive markers are lacking. The study aimed to determine whether abnormal DNA content predicts progression of oral dysplasia to carcinoma. Researchers matched OED cases to the Ontario Cancer Registry, performed a case–control DNA image cytometry comparison between progressed and non‑progressed lesions, and analyzed DNA content in a subset of resulting carcinomas. Eight percent of dysplasias progressed to carcinoma, and abnormal DNA content—detected in 28 of 99 lesions—predicted progression with a hazard ratio of 3.3, indicating it is a significant biomarker and likely represents a transient intermediate in oral cancer development.

Abstract

Oral epithelial dysplasia (OED) is a histologically detectable lesion that may progress to carcinoma but there are no accurate markers that predict progression. This study examined the development of carcinoma from oral dysplastic lesions, and the association between abnormal DNA content and progression to carcinoma. Epithelial dysplasias from the Oral Pathology Diagnostic Service were matched against the Ontario Cancer Registry database to identify cases that progressed to carcinoma. A case–control study was conducted to compare DNA image cytometry of dysplasias that progressed with those that have not progressed. For a subset of the progressed dysplasias, DNA content of the carcinoma was also analysed. A total of 8% of epithelial dysplasias progressed to carcinoma after 6–131 months. In all, 28 of 99 dysplasias showed abnormal DNA content by image cytometry. In multivariate analysis of time to progression, abnormal DNA content was a significant predictor with hazard ratio of 3.3 (95% confidence interval: 1.5–7.4) corrected for site and grade of dysplasia. Analysis of sequential samples of dysplasia and carcinoma suggested that epithelial cell populations with grossly abnormal DNA content were transient intermediates during oral cancer development. Abnormal DNA content is a significant biomarker of a subset of OED that progress to carcinoma.