Key Facts

Laryngeal cancer is one of the most common head and neck malignancies. It is strongly associated with smoking and alcohol use. Early glottic tumours have an excellent prognosis due to early presentation with hoarseness and high cure rates with radiotherapy.

Epidemiology

• Approximately 2,400 new cases/year in the UK
• Male:female ratio 4:1 (narrowing with changing smoking patterns)
• Peak incidence: 60-70 years
• Incidence declining in males (reduced smoking) but increasing in females
• 7th most common cancer in UK males

Aetiology

• Smoking: most important risk factor (10-30× risk)
• Alcohol: independent and synergistic risk factor with smoking
• HPV: minor role in laryngeal cancer (unlike oropharyngeal cancer)
• Occupational: asbestos exposure, paint fumes, wood dust
• GORD/laryngopharyngeal reflux: possible risk factor
• Previous radiation to the neck

Pathophysiology

• 95% are squamous cell carcinoma arising from mucosal epithelium

• Glottic (vocal cords — 65%): presents early due to hoarseness; lymphatic drainage poor → low rate of nodal metastasis at presentation
• Supraglottic (epiglottis, aryepiglottic folds, false cords — 30%): rich lymphatic drainage → higher rate of nodal metastasis; presents later
• Subglottic (below vocal cords — 5%): rare, poor prognosis due to late presentation
• Spread: local invasion → lymphatic (cervical nodes) → distant (lung most common metastatic site)
• Pre-malignant lesions: dysplasia, leucoplakia, erythroplakia may precede invasive cancer

Glottic Cancer (Most Common)

• Persistent hoarseness (earliest and most common symptom)
• Voice change progressing over weeks to months
• Stridor (advanced, airway obstruction)
• Dyspnoea

Supraglottic Cancer

• Dysphagia and odynophagia
• Referred otalgia (via Arnold's nerve, CN X)
• Muffled voice ('hot potato' voice)
• Neck lump (cervical lymphadenopathy — often the presenting feature)
• Late hoarseness (when tumour involves cords)

Subglottic Cancer

• Stridor (insidious onset)
• Dyspnoea
• Hoarseness (late)
• Often advanced at presentation

Red Flags

• Hoarseness >3 weeks (NICE NG12 — 2WW referral)
• Stridor
• Dysphagia with weight loss
• Haemoptysis
• Neck lump >3 weeks
• Otalgia with normal ear examination

Bedside

• Flexible nasendoscopy: visualise larynx, assess vocal cord mobility, identify mass
• Neck palpation for lymphadenopathy
• Voice assessment

Bloods

• FBC, U&Es, LFTs: baseline
• TFTs: baseline before neck radiotherapy

Imaging

• CT neck and chest with contrast: assess primary tumour extent, cervical lymph nodes, lung metastases
• MRI larynx: superior soft tissue detail, assess cartilage invasion and pre-epiglottic space
• PET-CT: for staging, detection of distant metastases, surveillance

Special Tests

• Panendoscopy with biopsy (EUA): definitive diagnosis — microlaryngoscopy with biopsy under GA
• TNM staging: critical for treatment planning
• Dental assessment: before radiotherapy (extract diseased teeth to prevent osteoradionecrosis)
• SALT assessment: swallow and voice assessment pre-treatment

Non-pharmacological

• MDT discussion: all cases
• Smoking and alcohol cessation: critical
• Nutritional support: dietitian, PEG/RIG if needed
• SALT: voice and swallow rehabilitation
• Psychological support: significant impact of diagnosis and treatment on quality of life

Radiotherapy

• Primary radiotherapy: first-line for early glottic cancer (T1-T2)
  • T1 glottic: 5-year cure rate >90% with voice preservation
  • T2 glottic: 5-year cure rate 70-80%
  • Typically 55-70Gy in 20-35 fractions
• Concurrent chemoradiotherapy: for T3-T4 laryngeal cancer (organ preservation)
  • Cisplatin 100mg/m² on days 1, 22, 43 with concurrent radiotherapy
  • RTOG 91-11 trial: chemoRT superior to induction chemo for larynx preservation

Surgical

• Transoral laser microsurgery (TLM): for early glottic cancers (T1-T2) — alternative to radiotherapy
• Partial laryngectomy: supraglottic laryngectomy, vertical partial laryngectomy
• Total laryngectomy: for advanced disease (T4), recurrence after radiotherapy
  • Permanent tracheostomy (end stoma)
  • Voice rehabilitation: tracheoesophageal puncture (TEP) + voice prosthesis (most common), oesophageal speech, electrolarynx
• Neck dissection: for cervical lymph node disease

Pharmacological

• Cisplatin: concurrent with radiotherapy for organ preservation
• Cetuximab: alternative to cisplatin if unfit for chemotherapy (NICE)
• Immunotherapy (pembrolizumab/nivolumab): for recurrent/metastatic disease (NICE TA661)

Referral Criteria

• 2-week wait ENT referral: hoarseness >3 weeks, neck lump >3 weeks (NICE NG12)
• MDT discussion: all confirmed laryngeal cancers
• Palliative care: for advanced/incurable disease

• T1 glottic: >90% 5-year survival (excellent)
• T2 glottic: 70-80% 5-year survival
• T3 glottic (organ preservation): 50-60% 5-year survival
• T4 laryngeal: 30-40% 5-year survival
• Supraglottic cancer: 50-60% 5-year survival (higher nodal metastasis rate)
• HPV status: less relevant in laryngeal cancer than oropharyngeal
• Continued smoking during radiotherapy reduces cure rates by 50%
• Voice preservation achieved in >60% with organ preservation protocols
• Total laryngectomy: significant impact on quality of life but excellent local control
• Second primary tumour risk: 3-5% per year

TNM Staging — Glottic Cancer (AJCC 8th Edition)

Landmark Trials in Laryngeal Cancer

Voice Rehabilitation After Total Laryngectomy