The HNSCC-SEQ Panel is an ultra-sensitive liquid biopsy solution for the identification of gene mutations in CDKN2A, EGFR, ERBB2, FGFR3, HRAS, KRAS, NOTCH1, PIK3CA, PTEN, and TP53 for emerging Head and Neck Squamous Cell Cancer (HNSCC) clinical applications. The HNSCC-SEQ Panel has been designed for human papillomavirus (HPV)-negative patients (~75% of HNSCC patients) and can be used to detect novel therapeutic targets and frequently occurring driver mutations for treatment response monitoring. The HNSCC-SEQ Panel delivers high-sensitivity mutation detection in HNSCC with a limit of detection of 0.05% MAF. Reliable detection of low-frequency mutations directly impacts the cost of clinical development.