Mutated in Circulating Tumor DNA As a Risk Level Biomarker in Head and Neck Squamous Cell Carcinoma Patients

Circulating tumor DNA (ctDNA) has been suggested as a surrogate biomarker for early detection of cancer recurrence. We aimed to explore the utility of ctDNA as a noninvasive prognostic biomarker in newly diagnosed head and neck squamous cell carcinoma (HNSCC) patients. Seventy HNSCC specimens were analysed for the detection of genetic alterations utilizing next-generation sequencing (NGS). mutations were revealed in 55 (79%). Upon detection of a significant mutation, circulating cell-free DNA was scrutinized for the presence of the tumor-specific mutation. ctDNA was identified at a minimal allele frequency of 0.08% in 21 out of 30 processed plasma samples. Detectable ctDNA correlated with regional spread (N stage ≥ 1, = 0.011) and poorer 5-year progression-free survival (20%, 95% CI 10.9 to 28.9, = 0.034). The high-risk worst pattern of invasion (WPOI grade 4-5) and deep invasion were frequently found in patients whose ctDNA was detected ( = 0.087 and = 0.072, respectively). Detecting mutated ctDNA was associated with poor progression-free survival and regional metastases, indicating its potential role as a prognostic biomarker. However, ctDNA detectability in early-stage disease and the mechanisms modulating its release into the bloodstream must be further elucidated.