A Systematic Review on Histopathological and Molecular Biomarkers in Oral Pathology:  Advancing Early Diagnosis of Precancerous and Cancerous Lesions

Abstract

Background: Precancerous and cancerous oral lesions (leukoplakia and erythroplakia) have shown a significant diagnostic challenge and were often faced with challenges due to clinically diverse presentations and overlapping with benign features. Despite the gold standard of histopathology, there were limitations in the subjective interpretation and the detection of early molecular changes. This systematic review evaluated the histopathological and molecular biomarkers to enhance the early diagnosis of oral lesions. Methods: A comprehensive search of studies published between 2015 and 2024 was conducted, following PRISMA guidelines. The electronic databases employed were Google Scholar, PubMed, and Science Direct. Studies that used histopathological or molecular biomarkers to assess diagnostic accuracy, sensitivity, specificity, and area under the curve (AUC) on humans were present in the criteria. The studies were excluded if they had inadequate data, examined non-oral lesions, or were based on animal models. Microsoft Excel 2022 was used to perform data extraction, and SPSS 2024 software was used to assess study quality. The risk of bias was assessed using the Evidence Project Risk of Bias Tool. Results: 15 studies were selected out of 98 studies screened, with predictive accuracies of 90.1% for Ki-67 and 96.2% for CK19, which were histopathological biomarkers. The noninvasive diagnostic potential of molecular biomarkers such as IL-6, LDH-A, and ctDNA was also promising (AUC > 0.8). Limitations included variability in methods, small sample sizes, and lack of standardization. Discussion: This review highlighted the role of histopathological and molecular biomarkers in the early diagnosis of oral lesions. Clinical implementation was hindered by inconsistencies in methodologies used and limited validation despite encouraging results.

Keywords

• Oral Cancer
• Precancerous Lesions
• Histopathology
• Molecular Biomarkers
• Early Detection