• Histologically confirmed diagnosis of SCC of the head and neck (excluding nasopharynx, nasal cavity/paranasal sinus, oral cavity, salivary, thyroid, and cutaneous primary malignancies).

‣ Any unknown primary SCC of the head and neck with radiographically detectable gross nodes is allowed (core or excisional biopsy acceptable; if excisional biopsy is performed, there must be residual radiographically detectable nodal disease; FNA may be acceptable only with PI and/or co-PI approval)

⁃ If the primary site is oropharynx or unknown primary, P16 IHC must be negative.

⁃ If the primary site is hypopharynx or larynx, any P16 status is acceptable (positive, negative, or unknown). P16 IHC is strongly encouraged when possible.

• Clinical stage T0-3 N1-2C M0 (AJCC 7th edition) without evidence of distant metastasis based on staging FDG PET/CT.

• 18 years of age or older.

• Must not have received prior radiation therapy or chemotherapy for HNC.

• Patients who have had their primary site tumor removed by surgery but still have residual grossly enlarged, radiographically detectable lymph nodes are eligible for this study.

• Karnofsky Performance Status (KPS) ≥ 70.

• CT or MRI of the Neck with and without contrast

• o Note: A CT scan of the Neck and/or a PET/CT performed for the purposes of radiation planning may serve as planning tools.

• Adequate hematologic function within 30 days prior to registration, defined as follows:

‣ White Blood Count (WBC) ≥ 2,000 cells/µL

⁃ Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3

⁃ Platelets ≥ 100,000 cells/mm3

⁃ Hemoglobin ≥ 8.0 g/dL; Note: The use of transfusion or other interventions to achieve Hgb ≥ 8.0 g/dL is acceptable

• Adequate renal function within 30 days prior to registration, defined as follows:

‣ Serum creatinine \< 1.5 mg/dL or creatinine clearance (CrCl) ≥ 50 mL/min determined by 24-hour collection or estimated by Cockcroft-Gault formula: CrCl male = \[(140 - age) x (weight in kg)\] / \[(Serum Cr mg/dL) x (72)\] CrCl female = 0.85 x (CrCl male)

⁃ Patients with serum creatinine \> 1.5 mg/dL can be eligible for carboplatin-based chemotherapy with approval of co-PI (Dr. Eric Sherman

• Adequate hepatic function within 30 days prior to registration, defined as follows:

‣ Bilirubin \< 2 mg/dL

⁃ AST or ALT \< 3 x the upper limit of normal

• Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential.

• The subject/legally authorized representative (LAR) must provide study-specific informed consent prior to study entry.