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

Inclusion Criteria:

* ECOG performance status of 0 or 1 or Karnofsky score 80-100.
* Preference is to register patients prior to surgery. However, if not registered prior to surgery, the patient can be registered prior to adjuvant therapy.
* Patients must have newly diagnosed, histologically or cytologically confirmed SCC or undifferentiated carcinoma of the oropharynx. Patients must have been determined to have resectable oropharyngeal disease. Patients with primary tumor or nodal metastasis fixed to the carotid artery, skull base or cervical spine are not eligible.
* Patients must be deemed eligible for a TOS procedure with no evidence of distant metastasis as determined by imaging studies. Metastatic disease may be evaluated using CT or PET/CT where appropriate; this can be performed with or without contrast. The following imaging is acceptable to evaluate the primary and regional disease:

  * CT Neck (with contrast preferred but not required)
  * PET/CT
  * MRI Neck (contrast preferred but not required)
* Patients must have 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. It is required that patients have a positive p16 IHC (as surrogate for HPV) status from either 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. Using p16 antibody obtained from Roche mtm laboratories AG (CINtec, clone E6H4) is recommended.
* 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 the following within the last 6 months prior to registration must be evaluated by a cardiologist and/or neurologist prior to entry into the study.

  * Congestive heart failure \> NYHA Class II
  * CVA/TIA
  * Unstable angina
  * Myocardial infarction (with or without ST elevation)
* Patients must have acceptable renal and hepatic function within 4 weeks prior to registration

  o For patients stratified following surgery and to concurrent chemotherapy (Arm CRT), calculated creatinine clearance must be \> 60 ml/min using the Cockcroft-Gault formula
* In patients with a contraindication to cisplatin, carboplatin can be used at time of patient enrollment if they are allocated to ARM CRT.

Exclusion Criteria:

* No evidence of extensive or "matted/fixed" pathologic adenopathy on preoperative imaging.
* Patients must not need a microvascular (free flap) reconstruction. Women must not be pregnant or breast-feeding due to the teratogenicity of chemotherapy. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
* Patient must not have an intercurrent illness likely to interfere with protocol therapy or prevent surgical resection
* Patients must not have uncontrolled diabetes, uncontrolled infection despite antibiotics, or uncontrolled hypertension within 30 days prior to registration.