For the early detection of recurrent disease, early driver mutations in HNSCC such as TP53 mutations would be favorable to use as biomarkers, as these are likely to occur consistently throughout clonal evolution [16, 17], and are found to be most frequent and concordant in recurrent and metastatic HPV-negative tumors compared to mutations in other genes [18–22]. Here, TP53 is linked to head and neck squamous cell carcinoma.