Given this current landscape of predictive biomarkers for use in HNSCC, we developed a targeted proteomics assay that quantifies markers for the following: (1) NRF2 signal transduction, (2) HNSCC tumor suppressors and oncogenes, (3) immuno-oncology signaling, and (4) HPV infection. Here, NFE2L2 is linked to head and neck squamous cell carcinoma.