Surgery Vs Chemoradiation for Oropharyngeal Cancer- A Phase II/III Integrated Design Randomized Control Trial

Inclusion Criteria: 1. Histopathology proven diagnosis of squamous cell carcinoma of the oropharynx, localized to the tonsil and/or lateralized tongue-base 2. ECOG Performance Status ≤2 3. Age ≥18 to 70 years 4. Anesthetic fitness obtained for surgery under general anesthesia 5. Resectable primary tumor with an anticipation of achieving resection free margins either by minimally invasive/open techniques 6. Clinical stage III or IV, i.e. T1-T2 or T3-T4 with N0-N3. Nodal disease withextranodal extension on clinical examination/imaging may be included at the surgeon's discretion, if the nodal disease is deemed resectable by the operating surgeon 7. HPV negative status determined by p16 status. 8. No distant metastases below the clavicles, based upon the following minimum diagnostic workup: 1. History/physical examination by the physician. 2. Imaging of the head and neck (Contrast enhanced MRI for local workup and Chest CT/PET-CT for distant metastatic workup) 9. Patients with no contraindications to Cisplatin chemotherapy and radiotherapy 10. Adequate organ function 1. Hematological- Hb\> 10 g/L, ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L. 2. Liver functions- bilirubin ≤ 2 x upper limit normal (ULN), AST/ALT/ ALP ≤ 2.5 x ULN, S. albumin ≥ 30 g/L. 3. Renal function- Creatinine ≤ 1.5 ULN, Creatinine clearance \> 50 mL/min. 11. Women of child bearing age should have a negative pregnancy test at the time of randomization and should be willing to use adequate contraception during the treatment phase of the trial 12. Patients who can be followed up and must be able to provide informed consent prior to study entry Exclusion Criteria: 1. Prior head and neck malignancy 2. Prior invasive malignancy, unless disease free for a minimum of 3 years 3. Prior chemotherapy for a different cancer administered within 3 years prior to registration 4. Patients who have received any neoadjuvant/ induction chemotherapy 5. Prior radiotherapy to the region of the head and neck that would result in overlap of radiation therapy fields 6. Unresectable primary or nodal disease involving the carotid vessels, prevertebral fascia or skull base 7. Large soft palate involvement \>1 cm 8. Deep extension into larynx, pre-epiglottic space and deep invasion into extrinsic muscles of tongue 9. Calculated GFR \< 50 cc/min 10. Patients who have uncontrolled cardiac comorbidity 1. QTc prolongation (a value of \>450 milliseconds) 2. Ejection fraction below 50% 3. Presence of regional wall akinesia 11. Presence of previous episode of thrombosis or embolism or presence of a prothrombotic condition in last 1 year 12. Presence of severe malnutrition as defined by body mass index of below 16kg per m2 or presence of weight loss of greater than 20% in last 6 months 13. Severe active co-morbidities such as severe cardiac failure, severe pulmonary compromise, type 1or 2 diabetes mellitus (Hb1ac of \> 8 mg/dl) severe and active infections or life expectancy less than 6 months 14. Prior allergic reaction to cisplatin 15. Radiographic evidence of retropharyngeal and/or level VI metastasis 16. Patients on other investigational drugs within last 30 days