Circulating Tumor DNA (ctDNA) in Saliva as a Prognostic Marker for OSCC Recurrence

Abstract

Oral squamous cell carcinoma remains a major global health concern due to its high recurrence rate and poor survival outcomes despite advances in treatment modalities. The emergence of liquid biopsy has opened new avenues for non-invasive cancer monitoring, with circulating tumor DNA gaining particular attention. Saliva, as a readily accessible biofluid, offers a unique advantage in oral malignancies due to its proximity to the tumor microenvironment. Salivary ctDNA reflects tumor-specific genetic and epigenetic alterations, enabling dynamic assessment of tumor burden, residual disease, and recurrence risk. Recent studies suggest that salivary ctDNA may provide superior sensitivity compared to plasma in detecting local disease changes. Its application in prognostication lies in its ability to identify minimal residual disease and predict recurrence earlier than conventional imaging or clinical examination. However, challenges such as lack of standardization, limited large-scale validation, and technical variability continue to hinder its routine clinical implementation. This review explores the biological basis, detection methodologies, and prognostic significance of salivary ctDNA in oral squamous cell carcinoma recurrence, highlighting current evidence and future perspectives in precision oncology.