Human papillomavirus-driven repression of NRF2 signalling confers chemo-radio sensitivity and predicts prognosis in head and neck squamous cell carcinoma.

Purpose: To investigate the role of NRF2 signalling in conferring superior prognosis in patients with HPV positive (HPV) head & neck squamous cell carcinomas (HNSCC) compared to HPV negative (HPV) HNSCC and develop molecular markers for selection of HPV HNSCC patients for treatment de-escalation trials.

Methods: NRF2 activity (NRF2, KEAP1, and NRF2-transcriptional targets), p16, and p53 levels between HPV HNSCC and HPV HNSCC in prospective and retrospective tumor samples as well as from TCGA database were compared. Cancer cells were transfected with HPV-E6/E7 plasmid to elucidate if HPV infection represses NRF2 activity and sensitizes to chemo-radiotherapy.