Radiotherapy, Carboplatin/Paclitaxel and Nivolumab for High Risk HPV-related Head and Neck Cancer

Inclusion Criteria * Histologically or cytologically proven squamous cell carcinoma of the oropharynx (tonsil, base of tongue, oropharyngeal wall, soft palate) that is p16 positive by immunohistochemistry or HPV positive by in situ hybridization * Clinical stage: stage III AJCC 8th edition staging (cT4 or cN3) OR "matted lymph nodes" (defined as 3 LNs abutting one another with loss of intervening fat plane that is replaced with evidence of extracapsular spread) * Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup: * History/physical examination, including documentation of weight within 2 weeks prior to registration; * FDG-PET/CT scan for staging and RT plan within 4 weeks prior to registration; Zubrod Performance Status 0-1 within 2 weeks prior to registration; * Age ≥ 18; * CBC/differential obtained within 2 weeks prior to registration on study, with adequate bone marrow function defined as follows: * Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3; Platelets ≥ 75,000 cells/mm3; Hemoglobin ≥ 9.0 g/dL AST/ALT \<3 x ULN * Total Bilirubin \<1.5 x ULN (except subjects with Gilbert Syndrome who must have a total bilirubin level \< 3 x ULN) * Serum creatinine within normal institutional limits or a creatinine clearance ≥ 45 mL/min within 2 weeks prior to registration; * Women of childbearing potential must agree to use a medically effective means of birth control throughout their participation in…