Comparative Analysis of TP53-Mutated Tumor DNA in Saliva and Plasma of Patients with Head and Neck Squamous Cell Carcinoma.

Liquid biopsy offers a promising noninvasive alternative for tissue sampling in solid cancers. Saliva, an easily accessible biofluid, can harbor tumor DNA, yet its clinical utility compared with plasma circulating tumor DNA (ctDNA) in head and neck squamous cell carcinoma (HNSCC) remains uncertain. Tumor samples from patients with HNSCC underwent next-generation sequencing to identify TP53 mutations. Matched plasma and saliva cell-free DNA (cfDNA) samples were analyzed for the presence of tumor-specific mutations. Pathologic features and survival data were evaluated in relation to mutation detectability in biofluids. Overall, TP53 mutations were detected in 64 of 85 tumors (75%). Liquid biopsy analysis included 36 plasma and 21 saliva samples from 40 patients. Plasma ctDNA was detected in 68% of oral cavity squamous cell carcinoma compared with 29% of laryngeal cancer cases, and it was associated with nodal metastases (P = 0.034). Detection of ctDNA showed a trend toward worse progression-free survival (37.4 versus 68.5 months; P = 0.134). Tumor mutation was identified in saliva cfDNA in 57% of cases, irrespective of disease stage or presence of regional metastases. Plasma ctDNA emerged as a potential prognostic marker in HNSCC, whereas mutated saliva cfDNA, although frequently detectable, lacked prognostic value or correlation with adverse pathologic features. Further research is warranted to elucidate the mechanisms governing tumor DNA shedding into saliva and to define its clinical applications.