Based on the immunofluorescence data, we dissected the functional significance of EphB4 and ephrinB2 expression by generating cancer cell-specific knockdowns of EphB4 or ephrinB2 using shRNA or CRISPR approach in both HPV-unrelated (Moc2, Ly2, and CUHN013) and E6-E7-driven HPV-like (MEER) HNSCC lines (Supplementary Fig. 4). This evidence concerns the gene EPHB4 and head and neck squamous cell carcinoma.