Our mouse model of HNSCC allows for conditional deletion of two important tumor suppressors in the oral epithelium: Transforming Growth Factor-β Receptor 1 (TGFβRI), an inhibitor of epithelial proliferation, and phosphatase and tensin homolog (PTEN), an enzyme that negatively regulates PI3K/Akt signaling to prevent uncontrolled cell growth. Here, PTEN is linked to head and neck squamous cell carcinoma.