Study Assessing The "Best of" Radiotherapy vs the "Best of" Surgery in Patients With Oropharyngeal Carcinoma

Main Inclusion Criteria:

* OPSCC in one of the following sub-sites: base of tongue, lateral pharyngeal wall, tonsil, glosso-tonsillar sulcus, vallecula or SGSCC in one or more of the following sub-sites: epiglottis, aryepiglottic fold, false cord or HPSCC in one or more of the following subsites: Lateral and medial wall of piriform sinus (sub-sites are defined as lateral (lateral pharyngeal wall, tonsil, glosso-tonsillar sulcus, lateral piriform sinus) vs. central lesions (base of tongue, vallecula, all supraglottic sites, medial wall of piriform sinus))
* TNM stage I-III (7th AJCC classification): T1 or T2, N0 or T1 or T2, N1 with one single neck node ≤ 3cm without radiographic signs of extracapsular extension (ECE), M0;
* TNM stage I for HPSCC: T1, N0, M0. ;
* Within 2 weeks before randomization, assessment by a Multi-Disciplinary Team (MDT) composed of at least a head and neck/ENT surgeon, oncologist, radiologist, radiotherapist, and pathologist of the treatment naïve patient and suitable for either TOS or IMRT based on:
* CT with contrast and/or MRI done within 4 weeks prior to randomization Note: Repeat contrast enhanced CT and/or MRI or US 1 week or less prior to randomization in case of suspicious nodes \<1cm on initial scan if per local practice
* Pan-endoscopy with assessment of trans-oral exposure for resection.
* peri-nodal infiltration either via CT-scan or MRI.
* Age 18 and older; Age 18 to 70 for SGSCC
* ECOG Performance status ≤ 2;
* Availability of biological material for HPV/p16 testing for OPSCCs
* Study information and Informed consent discussed by the surgeon and radio-oncologist and signed by the patient.
* Within 2 weeks prior randomization:
* Baseline MDADI score available;
* Adequate bone marrow function as demonstrated by neutrophils count \> 1,5 109 /L , platelets count \> 75 109 /L, WBC≥ 3.0 109 /L;
* Prothrombin time (PT) with an international normalized ratio (INR) ≤ 1.2
* Partial thromboplastin time (PTT) ≤ 1.2 times ULN
* Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test no more than 72 hours prior to randomization.
* Patients of childbearing / reproductive potential should agree to use adequate birth control measures for 3 months, especially if they will undergo any radiotherapy treatment at any time during the study. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.

Main Exclusion Criteria:

* Any previous anti-cancer therapy for HNSCC (surgery, chemo-, or radiotherapy or molecular targeted therapy);
* Any active malignancy (other than non-melanoma skin cancer or localized cervical cancer or localized and presumed cured prostatic cancer) within the last 5 years with ongoing systemic treatment
* Cancer in contact with the internal and/or common carotid artery
* Extension of OPSCC across the midline of the base-of-tongue
* Arytenoid involvement in case of SGSCC
* Infiltration of apex for piriform sinus in case of HPSCC
* Cancer originating from the soft palate or posterior pharyngeal wall
* Requirement of a reconstruction with a free or regional flap (i.e. involvement of \>50% of the soft palate)
* Pre-existing dysphagia not related to the oropharyngeal cancer or diagnostic biopsies
* Any psychological, cognitive, familial, sociological or geographical condition potentially hampering compliance with the study protocol, completion of patient reported measures and follow-up schedule; those conditions should be discussed with the patient before registration in the trial