It profiled 279 HNSCC samples and provided a large-scale landscape of genetic and epigenetic characterizations of HNSCC, pointing the pivotal roles of PIK3CA, TRAF3, E2F1, TP53, NOTCH and other regulators in Wnt signaling pathways in tumor-genesis of HNSCC. Here, TRAF3 is linked to head and neck squamous cell carcinoma.