De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal SCC: Follow-up Study

Inclusion Criteria: 1. ≥ 18 years of age (no upper age limit) 2. T0-3, N0 to N2c, M0 squamous cell carcinoma of the oropharynx 3. Biopsy proven squamous cell carcinoma that is HPV and/or p16 positive 4. ≤ 10 pack-years smoking history or ≤ 30 pack-years smoking history WITH ≥ 5 years abstinence from smoking 5. Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to treatment 6. ECOG Performance Status 0-1 7. CBC/differential obtained within 8 weeks prior to treatment, with adequate bone marrow function defined as follows: Platelets ≥ 100,000 cells/mm3; Hemoglobin ≥ 8.0 g/dl. 8. Adequate renal and hepatic function within 4 weeks prior to registration, defined as follows: Serum creatinine \< 2.0 mg/dl; Total bilirubin \< 2 x the institutional ULN; AST or ALT \< 3 x the institutional ULN. 9. Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential 10. Women of childbearing potential and male participants who are sexually active must practice adequate contraception during treatment and for 6 weeks following treatment. 11. Patients must be deemed able to comply with the treatment plan and follow-up schedule. 12. Patients must provide study specific informed consent prior to study entry Exclusion Criteria: 1. Prior history of radiation therapy to the head and neck 2. Prior history of head and neck cancer. 3. Unresectable disease (e.g. immobile node on physical exam, nodal disease that radiographically involves the carotid arteries, nerves) 4. Currently taking Disease Modifying Rheumatoid Drugs (DMRDs) 5. Severe, active co-morbidity, defined as follows: Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months; Transmural myocardial infarction within the last 6 months; Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration; Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects (Note, however, coagulation parameters are not required for entry into this protocol); Pre-existing ≥ grade 2 neuropathy; Prior organ transplant; Systemic lupus; Psoriatic arthritis. 6. Known HIV positive.