Rigotti Pietro, Polizzi Alessandro, Quinzi Vincenzo, Blasi Andrea, Lombardi Teresa, Lo Muzio Eleonora, Isola Gaetano
Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy.
Department of Life, Health & Environmental Sciences, Postgraduate School of Orthodontics, University of L'Aquila, 67100 L'Aquila, Italy.
Cancers (Basel). 2025 Jul 16;17(14):2366. doi: 10.3390/cancers17142366.
Oral squamous cell carcinoma (OSCC) remains one of the most common malignancies in the head and neck region, often preceded by a spectrum of oral potentially malignant disorders (OPMDs). Despite advances in diagnostic methods, reliable and non-invasive biomarkers for early detection and prognostic stratification are still lacking. In recent years, circulating cell-free DNA (cfDNA) has emerged as a promising liquid biopsy tool in several solid tumors, offering insights into tumor burden, heterogeneity, and molecular dynamics. However, its application in oral oncology remains underexplored. This study aims to review and discuss the current evidence on cfDNA quantification and mutation analysis (including TP53, NOTCH1, and EGFR) in patients with OPMDs and OSCC. Particular attention is given to cfDNA fragmentation patterns, methylation signatures, and tumor-specific mutations as prognostic and predictive biomarkers. Moreover, we highlight the challenges in standardizing pre-analytical and analytical workflows in oral cancer patients and explore the potential role of cfDNA in monitoring oral carcinogenesis. Understanding cfDNA dynamics in the oral cavity might offer a novel, minimally invasive strategy to improve early diagnosis, risk assessment, and treatment decision-making in oral oncology.
口腔鳞状细胞癌（OSCC）仍然是头颈部最常见的恶性肿瘤之一，通常之前会出现一系列口腔潜在恶性疾病（OPMDs）。尽管诊断方法有所进步，但仍缺乏用于早期检测和预后分层的可靠且非侵入性的生物标志物。近年来，循环游离DNA（cfDNA）已成为几种实体瘤中有前景的液体活检工具，可提供有关肿瘤负荷、异质性和分子动力学的见解。然而，其在口腔肿瘤学中的应用仍未得到充分探索。本研究旨在回顾和讨论关于OPMDs和OSCC患者中cfDNA定量和突变分析（包括TP53、NOTCH1和EGFR）的现有证据。特别关注cfDNA片段化模式、甲基化特征以及作为预后和预测生物标志物的肿瘤特异性突变。此外，我们强调了在口腔癌患者中标准化分析前和分析工作流程的挑战，并探讨了cfDNA在监测口腔癌发生中的潜在作用。了解口腔中cfDNA的动态变化可能会提供一种新的、微创的策略，以改善口腔肿瘤学中的早期诊断、风险评估和治疗决策。
