Vocal folds irregular mucosal changes: a multimodal evaluation for diagnosis and genetic risk stratification

PURPOSE: Irregular vocal fold mucosal changes pose diagnostic challenges and may range from benign to malignant. Emerging research highlights Sex-determining Region Y-box 2 (SOX2) gene amplification as a potential early marker in head and neck tumorigenesis. This work aimed to evaluate vocal fold irregular mucosal lesions for the early detection of high-risk lesions (high-grade dysplasia, carcinoma in situ, and squamous cell carcinoma (SCC)) and to explored the potential role of SOX2 gene in early laryngeal carcinogenesis. METHODS: This is a prospective observational cross-sectional study with a follow-up up to 2 years; 40 male patients with vocal fold irregularities were examined by laryngo-stroboscopy, then classified into two groups based on histopathological diagnosis: (A) Low-risk group (benign lesions, low-grade dysplasia), (B) High-risk group (high-grade dysplasia, carcinoma insitu and SCC. Real-time polymerase chain reaction PCR was performed to detect SOX2 gene expression. RESULTS: Significant differences were observed in vocal fold stroboscopic features (mucosal wave and amplitude), and SOX2 gene expression across lesion groups, with higher SOX2 expression noted in the high-risk group (P < 0.05). A strong positive correlation was observed between histopathological severity and each of stroboscopic impairment in mucosal wave and amplitude, and Log SOX2 gene expression. The regression analysis showed a significant independent predictive effect of SOX2 gene expression on the progression to high-risk lesions. CONCLUSIONS: This study integrated established diagnostic standards, laryngostroboscopy for clinical assessment, and histopathology as the gold standard for grading, while the analysis of SOX2 gene expression showed a promising predictive molecular marker for tumorigenesis.