Risk-adapted Therapy in HPV+ Oropharyngeal Cancer Using Circulating Tumor (ct)HPV DNA Profile - The ReACT Study

Inclusion Criteria: * Participants must meet the following eligibility criteria at the time of screening to be eligible to participate in the study: * Subject must have histologically or cytologically confirmed, stage I, II, or III (N3 disease excluded), HPV associated oropharyngeal (tongue base or tonsil) squamous cell carcinoma, as defined by 2017 American Joint Committee on Cancer (AJCC), 8th edition staging. \-- Patients with HPV-associated disease of unknown primary (cT0) are eligible * HPV status should be confirmed on tissue biopsy or cytologic sample by any of the following: * Immunohistochemical staining for p16 with ≥70% expression * Confirmatory DNA testing (PCR or ISH) for high-risk subtype * Willing to provide blood and tissue from a diagnostic biopsy and blood samples before, during, and after treatment. * Detectable HPV ctDNA blood sample at baseline, prior to treatment, using the NavDx® assay that detects HPV subtype 16 * Age 22 years or older * ECOG performance status ≤ 2 * Participants should have adequate organ and marrow function if they are to receive chemotherapy (cisplatin, or carboplatin and paclitaxel) with radiation concurrently as determined by standard institutional guidelines and investigator preference (parameters suggested below). * absolute neutrophil count (ANC) ≥ 1000 * platelet count ≥ 100,000 * total bilirubin of 1.5 or less * creatinine of 1.6 or less (or a CrCl ≥50 mL/min) per institutional standards. * Planning to recei…