This study seeks to study the population of HPV-related oropharynx cancer patients that appear to be at highest risk for treatment failure with loco-regional failure and distant metastases including cT4 or cN3. The study team aims to determine if it is feasible to use multi-modality imaging (both DCE MRI and FDG-PET) to optimize the radiation boost in high risk p16+ OPSCC with similar or decreased toxicity compared to historic standard therapy.

Inclusion Criteria:

• Patients must have pathologically confirmed, locally/regionally advanced p16+ squamous cell carcinoma of the oropharynx referred for definitive chemo-RT
• AJCC 8 Stage III (cT4 or N3)
• ECOG 0-1 performance status within two weeks of enrollment
• Pre-treatment laboratory criteria within four weeks of enrolment: WBC > 3500/ul, granulocyte > 1500/ul. Platelet count > 100,000/ul. Total Bilirubin < 1.5 X ULN. AST and ALT < 2.5 X ULN. Estimated Creatinine clearance >30cc/min
• Patients must be able to receive protocol chemotherapy in the judgment of the treating Medical Oncologist
• Age >18
• All patients must be informed of the investigational nature of this study and given written informed consent in accordance with institutional and federal guidelines.
• Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study.

Exclusion Criteria:

• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
• Patients should have no contraindications to having a contrast enhanced MRI scan. These contraindications will be assessed at the time of enrollment using the guidelines set up and in clinical use by the Institutional Standard Practice.
• Patients should have no contraindications to having a contrast enhanced PET scan. These contraindications will be assessed at the time of enrollment using the guidelines set up and in clinical use by the Institutional Standard Practice.
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible).
• Any prior therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable if > 3 years prior to study;