NRF2 dysregulation due to mutations in the NRF2 pathway (NRF2, KEAP1, and CUL3) is present in more than 1/3 of HNSCC negative to human papillomavirus (HPV), while in HNSCC positive to HPV, the rate of mutation in NRF2 pathway was extremely low or none [202]. Here, NFE2L2 is linked to head and neck squamous cell carcinoma.