These results highlight the potential for combination anti-HER2 and anti-EGFR inhibition in HNSCC and in cancers that overexpress both HER2 and EGFR (i.e. ovarian cancer and trastuzumab resistant HER2+ breast cancer) to decrease tumor proliferation, improve overall patient prognosis, and inform on overall clinical decision making through a combination of low, nontherapeutic doses of therapy. This evidence concerns the gene EGFR and head and neck squamous cell carcinoma.