Determination of Cetuximab Versus Cisplatin Early and Late Toxicity Events in HPV+ OPSCC

Inclusion Criteria: * American Joint Committee on Cancer (AJCC) TNM Stage III-IVa (T3N0-T4N0, and T1N1-T4N3) oropharyngeal squamous cell carcinoma (SCC) tumours * Clinical multidisciplinary team decision to treat with primary curative cisplatin chemoradiotherapy * No previous treatment including surgery, except node biopsies or diagnostic tonsillectomy * Medically fit (ECOG 0, 1 or 2) * Adequate cardiovascular, haematological, renal and hepatic function * Age \> 18 years * Written informed consent given * Using adequate contraception \[male and female participants\]. Must take contraceptive measures during, and for at least six months after treatment. Exclusion Criteria: * Distant metastasis (i.e. AJCC TNM stage IVc disease) * AJCC TNM Stage T1-2N0 disease * Treated with primary radical surgery to the primary site (e.g. resection) * Concurrent use of CYP3A4 inducers or inhibitors. \[A standard course of dexamethasone or aprepitant for the prevention of cisplatin-induced nausea and vomiting is permitted\] * Serious cardiac illness or other medical conditions precluding the use of cisplatin or cetuximab \[no history of clinically significant cardiac disease, serious arrhythmias, or significant conduction abnormalities; no uncontrolled seizure disorder; no active neurologic disease; no neuropathy greater than grade 1\] * Patients who have p16+ tumours who also have N2b, N2c or N3 nodal disease and whose lifetime smoking history is also more than 10 pack years (i.e. have both risk factors). * Pregnant or lactating * Previous treatment for any other cancer with cytotoxics, radiotherapy or anti-EGFR therapies * Inadequate renal, haematological or liver functions \[Absolute neutrophil count \<1,500/mm3; platelet count \<100,000/mm3; WBC \<3,000/mm3; haemoglobin \<9 g/dL. \[Haemoglobin correction by transfusion permitted.\] Bilirubin \> 1.5 times upper limit of normal (ULN); alkaline phosphatase \> 2.5 times ULN; AST and ALT \> 2.5 times ULN. Creatinine \> 1.5 mg/dL; Creatinine clearance \< 60 mL/min\] * Patients with clinically significant hearing impairment * Life expectancy less than 3 months * Other malignancy within the past 3 years except basal cell skin cancer or pre-invasive carcinoma of the cervix.