Herein, we also report that tumors with simultaneous shallow (single copy) losses at both, CYLD and TRAF3, loci were robustly associated with high expression of the sky blue (NF-κB) module (Fig. 4), suggesting that mechanisms in addition to deep deletion of TRAF3 or CYLD modulate NF-κB activation in HPV+ HNSCC. Here, TRAF3 is linked to head and neck squamous cell carcinoma.