On the Cutting Edge of Oral Cancer Prevention: Finding Risk-Predictive Markers in Precancerous Lesions by Longitudinal Studies

Abstract

Early identification and management of precancerous lesions at high risk of developing cancers is the most effective and economical way to reduce the incidence, mortality, and morbidity of cancers as well as minimizing treatment-related complications, including pain, impaired functions, and disfiguration. Reliable cancer-risk-predictive markers play an important role in enabling evidence-based decision making as well as providing mechanistic insight into the malignant conversion of precancerous lesions. The focus of this article is to review updates on markers that may predict the risk of oral premalignant lesions (OPLs) in developing into oral squamous cell carcinomas (OSCCs), which can logically be discovered only by prospective or retrospective longitudinal studies that analyze pre-progression OPL samples with long-term follow-up outcomes. These risk-predictive markers are different from those that prognosticate the survival outcome of cancers after they have been diagnosed and treated, or those that differentiate between different lesion types and stages. Up-to-date knowledge on cancer-risk-predictive markers discovered by longitudinally followed studies will be reviewed. The goal of this endeavor is to use this information as a starting point to address some key challenges limiting our progress in this area in the hope of achieving effective translation of research discoveries into new clinical interventions.

Keywords: DNA methylation; epigenetic; genetic mutation; long-term follow-up; risk assessment; translational study.

Figure 1

Schematic diagrams of biomarkers in oral carcinogenesis. Diagrams depicting diagnostic markers for differentiating different lesion types (A), predictive markers for assessing the risk of oral premalignant lesions in developing cancer (B), and prognostic markers for predicting the outcome of oral cancer (C). Abbreviations: LG, low-grade; HG, high-grade; OD-P, progressive oral dysplasia; OD-S; static oral dysplasia. Nuclei in (A) are labeled with different color schemes to indicate mitotic cells (orange), low-grade dysplastic cells (pink), high-grade dysplastic cells (red), low-grade malignant cells (light blue), and high-grade malignant cells (dark blue). Nuclei in (B) are labeled in red to indicate cells expressing high-risk markers for malignant progression. Nuclei in (C) are labeled in green to indicate malignant cells.