• Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma of the head and neck that has arisen from the oral cavity, oropharynx, nasal cavity, paranasal sinuses, larynx, or hypopharynx

• Clinical stage T1, N2-3; T2, N1-3, T3/T4a, Any N (AJCC, 8th ed.) without evidence of distant metastasis (M0) based on PET/CT or CT chest, abdomen, and pelvis, for which standard-of-care treatment would entail surgical resection with adjuvant radiation +/- chemotherapy.

• ° Patients with recurrent and multiple primary head and neck cancers that are surgically resectable are eligible if the patient did not receive prior radiation or systemic therapy.

• Disease must be amenable to surgical resection.

• The patient must be a surgical candidate.

‣ Hemoglobin \> 9.0 g/dL

⁃ Absolute neutrophil count (ANC) \>1.5 x 10\^9/L

⁃ Platelet count \>100 x 10\^9/L

⁃ Serum creatinine \<1.5 upper limit of normal (ULN) or estimated creatinine clearance (CrCl) \>30 mL/min

⁃ Adequate hepatic function:

• Total bilirubin \<1.5 x upper limit of normal ULN)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both \< 3 x ULN

• Alkaline phosphatase (ALP) \<2.5 x ULN Note: For patients with Gilbert syndrome, total bilirubin \<3x ULN. Upper central must be documented appropriately as past medical history.

• Men and woman \>18 years old

• Eastern cooperative oncology group performance status \< 1