De-escalation of Radiation Dose in HPV-associated OPC Utilising FMISO PET (DE-RADIATE)

Inclusion Criteria: * Age \> 18 years * Histologically confirmed cT1-2N1-2b oropharyngeal squamous cell carcinoma or cTxN1-2 carcinoma of unknown primary * p16 positive (70% nuclear and cytoplasmic staining) and HPV positive (genotyping via PCR) tumours of the tonsil, base of tongue, glossotonsillar sulcus, or unknown primary site (suspected mucosal origin). * No contraindications to radiotherapy, platinum-based chemotherapy or surgery * No contraindications to PET/CT or MRI * Eastern Cooperative Oncology Group (ECOG) performance status score 0-2 (KPS \> 70%) * Ability to understand and willingness to sign a written informed consent document Exclusion Criteria: * Women lactating, pregnant or of childbearing potential who are not willing to avoid pregnancy during the study * Patients with a history of severe renal disease(s) (eGFR \<20) than cannot tolerate gadolinium chelate contrast agents.) * ECOG ≥ 3 * Previous high dose radiation therapy to the head or neck * Patients unwilling or unable to have PET/CT or MRI * Geographically remote patients unable to agree to imaging schedule * Patients with a history of psychological illness or condition such as to interfere with the patient's ability to understand the requirements of the study. * Patients with significant cardiac or pulmonary disease including cardiac arrythmias or Chronic Obstructive Pulmonary Disease (COPD) that are unable to tolerate high flow O2 for oxygen contrast. * Patients taking carbonic anhydrase inhibitors (acetazolamide) * History of glaucoma * Any implant, foreign body, 3T MRI incompatible device, or other contraindication to MRI imaging