Our laboratory uses several murine models to study HPV(+) HNSCC: A primary tumor model derived from mouse oropharyngeal epithelial cells stably expressing the HPV oncogenes, E6 and E7, H-Ras, and luciferase (mEERL) [24,25,26,27], and an aggressive, treatment resistant, R/M model derived from a spontaneously arising lung metastasis in a mouse that was implanted with a mEERL tumor and failed chemoradiation treatment (MLM3) [28]. The gene discussed is HRAS; the disease is head and neck squamous cell carcinoma.