Key Facts

Head and neck cancers are a heterogeneous group of malignancies arising from the mucosal lining of the upper aerodigestive tract. They are predominantly squamous cell carcinomas and are strongly associated with smoking, alcohol use, and increasingly HPV infection. Early detection and multidisciplinary management are essential.

Epidemiology

• Approximately 12,000 new cases/year in the UK
• 8th most common cancer in UK males
• Male:female ratio 2-3:1 (narrowing due to changing smoking and HPV patterns)
• Incidence increasing, particularly HPV-related oropharyngeal cancer
• Peak age: >50 years for smoking/alcohol-related; 40-60 years for HPV-related

Aetiology

• Smoking: strongest risk factor; dose-dependent (pack-years)
• Alcohol: independent and synergistic risk with smoking (15× combined risk)
• HPV (particularly HPV-16): major cause of oropharyngeal cancer (tonsil, base of tongue)
• Betel nut chewing: oral cavity cancer (South Asian populations)
• EBV: nasopharyngeal carcinoma (Southern Chinese populations)
• Other: occupational exposure (hardwood dust — sinonasal adenocarcinoma), radiation, immunosuppression

Pathophysiology

• 90% are squamous cell carcinomas arising from mucosal epithelium

• Field cancerisation: entire mucosal field exposed to carcinogens, predisposing to multiple primary tumours
• HPV-positive cancers: HPV E6 and E7 oncoproteins inactivate p53 and Rb, driving carcinogenesis in lymphoid tissue (tonsils, base of tongue)
• Spread: local invasion, lymphatic (cervical lymph nodes), distant metastases (lung, liver, bone — rare at presentation)
• HPV-positive tumours have different biology: better response to treatment, better prognosis

Symptoms by Subsite

• Oral cavity: persistent ulcer, white/red patch (leucoplakia/erythroplakia), lump, pain, loose tooth, difficulty with dentures
• Oropharynx: sore throat, dysphagia, referred otalgia, neck lump (often the presenting complaint in HPV-related disease)
• Larynx: hoarseness (glottic), stridor (subglottic), dysphagia (supraglottic)
• Hypopharynx: dysphagia, odynophagia, weight loss, referred otalgia, neck lump (often late presentation)
• Nasopharynx: nasal obstruction, epistaxis, OME (unilateral), cranial nerve palsies

Red Flags (2-Week Wait — NICE NG12)

• Unexplained neck lump >3 weeks
• Hoarseness >3 weeks
• Persistent oral ulcer >3 weeks
• Unexplained unilateral otalgia with normal otoscopy
• Persistent unexplained dysphagia
• White or red patch in oral cavity
• Cranial nerve palsy with neck lump

Examination

• Full head and neck examination including oral cavity, oropharynx
• Flexible nasendoscopy (visualise nasopharynx, hypopharynx, larynx)
• Neck palpation: cervical lymphadenopathy (levels I-VI)
• Cranial nerve assessment

Bedside

• Flexible nasendoscopy: visualise primary tumour
• Oral cavity examination
• Fine needle aspiration (FNA) of neck lump (USS-guided)

Bloods

• FBC, U&Es, LFTs: baseline and nutritional status
• EBV serology: if nasopharyngeal carcinoma suspected
• TFTs: baseline before neck radiotherapy

Imaging

• CT neck and chest with contrast: staging of primary and regional disease, lung metastases
• MRI: superior soft tissue detail for oral cavity, oropharynx, nasopharynx
• PET-CT: for staging, detection of occult primary, assessment of treatment response, surveillance
• Orthopantomogram (OPG): dental assessment before radiotherapy

Special Tests

• Panendoscopy (EUA): examination under anaesthesia with biopsy — definitive histological diagnosis
• p16 immunohistochemistry: surrogate marker for HPV status in oropharyngeal SCC
• HPV DNA testing: confirmatory for HPV-related cancer
• TNM staging: guides treatment and prognosis

Non-pharmacological

• MDT discussion: all head and neck cancers managed via MDT (surgeon, oncologist, radiologist, pathologist, CNS, SALT, dietitian)
• Nutritional support: dietitian input; PEG/RIG tube if unable to swallow
• Speech and language therapy: pre- and post-treatment swallow and voice rehabilitation
• Dental assessment: prior to radiotherapy (extractions before RT to prevent osteoradionecrosis)
• Smoking cessation: essential
• Psychological support: CNS, psychologist, support groups

Pharmacological

• Chemotherapy: cisplatin 100mg/m² 3-weekly (radiosensitiser) with concurrent radiotherapy
• Cetuximab (anti-EGFR): alternative to cisplatin in patients unfit for chemotherapy
• Immunotherapy: pembrolizumab/nivolumab (anti-PD-1) for recurrent/metastatic disease (NICE TA661)

Surgical

• Primary surgery: resection of tumour with adequate margins
  • Oral cavity: glossectomy, mandibulectomy, maxillectomy
  • Larynx: partial or total laryngectomy
  • Reconstructive surgery: free flap (radial forearm, fibula, anterolateral thigh)
• Neck dissection: for regional lymph node management (selective, modified radical, or radical)
• Transoral robotic surgery (TORS): for oropharyngeal tumours (minimally invasive)
• Transoral laser microsurgery (TLM): for early glottic and supraglottic cancers

Radiotherapy

• Primary radiotherapy: for early laryngeal cancer (T1-T2 glottic — voice preservation), nasopharyngeal cancer
• Adjuvant radiotherapy: post-operative for advanced disease, positive margins, extranodal extension
• Concurrent chemoradiotherapy: standard for locally advanced disease (organ preservation protocols)
• Intensity-modulated radiotherapy (IMRT): reduces parotid gland dose, minimising xerostomia

Referral Criteria

• 2-week wait ENT referral: as per NICE NG12 criteria (above)
• MDT discussion: all confirmed head and neck cancers
• Palliative care: for advanced/incurable disease

• Overall 5-year survival: approximately 50-60%
• Early stage (T1-T2, N0): >80% 5-year survival
• HPV-positive oropharyngeal cancer: >80% 5-year survival (significantly better than HPV-negative)
• HPV-negative oropharyngeal cancer: <50% 5-year survival
• Early glottic carcinoma (T1): >90% 5-year survival with radiotherapy alone
• Hypopharyngeal cancer: worst prognosis among H&N sites; 30-35% 5-year survival (often late presentation)
• Factors affecting prognosis: stage at presentation, HPV status, comorbidities, smoking during treatment
• Second primary tumour risk: 3-5% per year (field cancerisation)

HPV-Positive vs HPV-Negative Oropharyngeal Cancer

NICE NG12 — 2-Week Wait Referrals for H&N Cancer