Emerging Proximal Liquid Biopsy Approaches for Detecting Residual Disease and Predicting Recurrence in Head and Neck Cancer: A Review and Proposal of Novel Liquid Staging.

Abstract

Head and neck squamous cell carcinoma remains challenging due to high recurrence rates and poor survival outcomes. Developing precise technologies for disease burden assessment, treatment response, and minimal residual disease (MRD) surveillance is crucial for improving prognosis. This review explores the potential of liquid biopsy for MRD and recurrence detection. A novel liquid TNM (LiTNM) staging system is introduced, integrating biomarkers from saliva, surgical drain lymphatic fluid (SLF), and peripheral blood. Proximal liquid biopsies, particularly saliva and SLF, offer advantages due to their proximity to the tumor microenvironment. Saliva demonstrates high sensitivity in HPV-associated oropharyngeal cancers, while SLF holds potential in identifying early postoperative recurrence. Despite these advancements, standardization and validation remain challenges. Liquid biopsy approaches show promise for postoperative disease monitoring, yet their clinical implementation remains in the early stages. The proposed LiTNM staging system could complement TNM staging by providing a molecular framework for risk stratification. However, rigorous prospective studies are necessary to validate its clinical utility and facilitate adoption.