While p16-IHC has been used as a surrogate marker for HPV status and research is ongoing to find novel biomarkers for HNSCC to predict outcomes of treatment, biomarkers are more urgently needed for HPV-negative HNSCC patients, as these patients have poor outcomes compared to HPV-positive HNSCC patients. This evidence concerns the gene CDKN2A and head and neck squamous cell carcinoma.