Circulating Tumor DNA (ctDNA) in Locally Advanced Head and Neck Squamous Cell Carcinoma

Inclusion Criteria: * Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information. Consent for the use of any residual material from biopsy and/or surgical resection (archival tissue) and serial blood draws will be required for enrollment. * Age ≥ 18 years of age on day of signing informed consent * Newly diagnosed, histologically confirmed squamous cell carcinoma of the head and neck, including the following subtypes: oral cavity, oropharynx, larynx * Must be planning to undergo gross total resection of the primary tumor with curative intent at UNC-CH hospital * No prior, definitive therapy to primary tumor. Must meet one of the following clinical stages: T3-T4 (if T1/T2 must have nodal involvement), Any N, M0 * Patient must be amenable to receiving adjuvant therapy with radiotherapy +/- systemic therapy, as clinically indicated, based on either standard of care (SOC) or appropriate clinical trial. * Diagnostic tumor material must be available for correlative analysis * Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee Exclusion Criteria: * Has known evidence of metastatic disease based on clinical or radiographic studies * Women who are pregnant or nursing * History of another primary malignancy in the last 5 years prior to registration. Patients with history of in situ cancer or basal or localized squamous cell skin cancers are eligible. * Patients with primary skin cancers of the head and neck, including basal or squamous cell cancers * Prior chemotherapy, IP, biologic, or hormonal therapy for HNSCC treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.