TRAF3, an E3 ligase, is a negative regulator of both canonical and non-canonical NFκB activity [85, 86]; mutations in TRAF3, or the loss of TRAF3, results in enhanced NFκB signalling and promoted HPV + HNSCC development [83, 86, 87]. The gene discussed is TRAF3; the disease is head and neck squamous cell carcinoma.