Oropharyngeal squamous cell carcinoma (OPSCC) incidence is increasing rapidly in the developed world. This has been attributed to a rise in Human Papillomavirus (HPV) infection. HPV+OPSCC is considered a distinct disease entity, affecting younger patients and has a good prognosis following treatment. Subsequently, patients can live with the considerable side effects for several decades.

Radiotherapy and cetuximab (Epidermal Growth Factor Receptor-inhibitor) have demonstrated similar efficacy to 'platin' chemoradiotherapy (current standard treatment containing platinum-based compounds) in head and neck cancer, but is potentially less toxic.

Results of this trial will be used to determine the optimum treatment of this debilitating cancer, with the primary aim of decreasing toxicity and improving quality of life for HPV+OPSCC patients.

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.