Phase 2 Pragmatic Trial of Sentinel Lymph Node Biopsy (SLNB) in Patients With Clinically Node-Negative (cN0), High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) of the Head and Neck

Inclusion Criteria: 1. Must have histologically and/or biochemically confirmed head and neck cSCC 2. Must have head and neck cSCC categorized as high risk: 1. Location in the ear or the lip, 2. Diameter greater than 2 cm, 3. Depth greater than 4 mm, 4. Perineural invasion, 5. Poorly differentiated, and/or 6. Recurrent disease 3. Lymph-node negative (cN0) status confirmed by computed tomography (CT) imaging. 4. Candidate for surgical intervention with sentinel lymph node biopsy (SLNB) and potential lymphadenectomy for treatment of cSCC. 5. Zubrod Performance Status 0-2 6. Age ≥18 years at time of consent. 7. Provision of signed and dated informed consent form. 8. Stated willingness to comply with all study procedures and availability for the duration of the study. Exclusion Criteria: 1. Other active cancers. 2. Definitive clinical or radiologic evidence of regional (cervical) and/or distant metastatic disease. 3. Prior non-head and neck invasive malignancy (except non-melanomatous skin cancer, including effectively treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or cervix) unless disease free for ≥ 2 years. 4. Diagnosis of head and neck mucosal SCC. 5. Prior systemic chemotherapy for head and neck mucosal SCC; note that prior chemotherapy for a different cancer is allowable. 6. Prior radiotherapy to the head and neck that would result in overlap of radiation therapy fields. 7. Patient with severe, active co-morbidity that would preclude a lymphadenectomy. 8. Pregnant or breast-feeding persons. 9. Prior surgery involving the lateral neck, including neck dissection or gross injury to the neck that would preclude surgical dissection for this trial. Prior thyroid and central neck surgery is permissible; biopsy is permitted. Prior surgery for confirmation of tumor pathology is permitted. Note: Borderline suspicious nodes that are ≥1 cm with radiographic finding suggestive of NOT malignant should be biopsied using U/S-guided fine-needle aspirate (FNA) biopsy. 10. Underlying or documented history of hematologic malignancy (e.g., chronic lymphocytic leukemia) or other active disease capable of causing lymphadenopathy (sarcoidosis or untreated mycobacterial infection). 11. Actively receiving systemic cytotoxic chemotherapy, immunosuppressive, anti-monocyte, or immunomodulatory therapy. 12. Currently participating in another investigational therapeutic trial.