Transoral Surgical Resection Followed by De-escalated Adjuvant IMRT in Resectable p16+ Locally Advanced Oropharynx Cancer

Eligibility Criteria

• * ECOG performance status of 0 or 1 or Karnofsky score 80-100.
• * Newly diagnosed, histologically or cytologically confirmed SCC or undifferentiated carcinoma of the oropharynx and resectable oropharyngeal disease.
• * Patients must be deemed eligible for a TOS procedure with no evidence of distant metastasis as determined by imaging studies.
• * Biopsy-proven p16+ oropharynx cancer; the histologic evidence of invasive squamous cell carcinoma may have been obtained from the primary tumor or metastatic lymph node.
• * Carcinoma of the oropharynx associated with HPV as determined by p16 protein expression using immunohistochemistry (IHC) performed by a CLIA approved laboratory.
• * No prior radiation above the clavicles.
• * Patients with a history of a curatively treated malignancy must be disease-free for at least two years except for carcinoma in situ of cervix, melanoma in-situ (if fully resected), and/or non-melanomatous skin cancer.
• * Patients with congestive heart failure \> NYHA Class II, CVA/TIA, unstable angina, or myocardial infarction within the last 6 months prior to registration must be evaluated by a cardiologist and/or neurologist.
• * Acceptable renal and hepatic function within 4 weeks prior to registration as predefined.
• * No evidence of extensive or "matted/fixed" pathologic adenopathy on preoperative imaging.
• * Women must not be pregnant or breast-feeding due to the teratogenicity of chemotherapy.
• * No intercurrent illness likely to interfere with protocol therapy or prevent surgical resection.
• * No uncontrolled diabetes, infection despite antibiotics, or hypertension within 30 days prior to registration.