Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Background: Liquid biopsy is emerging as a promising minimally-invasive substitute for tissue sampling. It can be analysed for the detection of cancer-specific gene mutations, denoted as tumor DNA (tDNA). Saliva, a readily accessible and easily obtainable fluid, can potentially provide an optimal source for tDNA identification in head and neck cancer, particularly in early-stage oral cavity tumors. The aims of this study were to test the feasibility of using genetic analysis of various biofluids for the detection of tDNA and to assess its prognostic value.
Materials and Methods: Next-generation sequencing (NGS) was utilized to detect somatic alterations in the coding regions of TP53 gene in head and neck squamous cell carcinoma (HNSCC) samples. Upon the identification of a significant TP53 mutation, cell free DNA in plasma and saliva samples was scrutinized for the presence of the tumor-specific mutation. Demographic data, pathological features and clinical outcomes were analysed in relation to tDNA detectability in the biofluids.
Results: Significant somatic mutations in TP53 were detected in 64 out of 85 HNSCC specimens analysed by NGS (75%). Liquid biopsies were collected from 40 patients (including 35 plasma and 21 saliva samples), who had oral cavity (31), laryngeal (8) and HPV-negative oropharyngeal (1) cancers. Eleven patients (27.5%) had an early-stage disease. Plasma tDNA was identified in 68% of oral cavity tumors compared to 29% of laryngeal cancers (P=0.058). Neither disease stage nor tumor size correlated with plasma tDNA detection, while cervical metastases were associated with detectable plasma tDNA (P=0.034). Worst pattern of invasion IV-V was recorded more frequently when plasma tDNA was detected (76%, P=0.057). A trend of poorer progression free survival (PFS) was observed for patients whose plasma tDNA was identified (37.4 months vs. 68.5 months, Log-rank, P=0.176). Detection rate of tDNA in saliva was 57%, with comparable rates for oral cavity tumors (9/13, 64%) and laryngeal tumors (3/7, 43%), regardless of disease stage or primary tumor dimensions. No correlation with survival outcomes was observed. The concordance between saliva and plasma tDNA identification was found to be only 29.4%.
Conclusion: Detection of saliva-based tDNA had no prognostic value in this cohort, while plasma-based tDNA identification correlated with regional spread of disease and poorer PFS. Despite the promise of saliva testing, the biology of tDNA should be further elucidated before saliva-based genetic diagnostics can be clinically used for prognostication or surveillance of HNSCC patients.