Laryngeal Cancer

Malignancy of the larynx, of which over 95 percent is squamous cell carcinoma. It accounts for around a third of all head and neck cancers and is one of the few malignancies where an early symptom, hoarseness, appears while the tumour is small and highly curable.

Anatomical subsites and why they behave differently

The behaviour, presentation, spread and prognosis of laryngeal cancer are determined almost entirely by embryological anatomy.

• Supraglottis, from the tip of the epiglottis to the laryngeal ventricle, including the epiglottis, aryepiglottic folds, arytenoids and false cords. It derives from the buccopharyngeal anlage and has a rich bilateral lymphatic network draining to levels II and III bilaterally. Consequently, supraglottic tumours present late with vague symptoms and have a 30 to 50 percent rate of occult nodal metastasis at presentation, frequently bilateral. Around 30 to 35 percent of laryngeal cancers.
• Glottis, comprising the true vocal folds and the anterior and posterior commissures, extending 1 cm below the free edge. It derives from the tracheobronchial anlage and has almost no lymphatic drainage, which is the single most important anatomical fact in this disease. Glottic tumours therefore present early with hoarseness, metastasise late, and have occult nodal disease in under 5 percent for T1 lesions. Around 60 to 65 percent of laryngeal cancers, and the group with the best prognosis, with 5 year survival above 90 percent for T1.
• Subglottis, from 1 cm below the vocal folds to the inferior border of the cricoid. Lymphatic drainage is to the paratracheal and level VI nodes and to the mediastinum. Tumours present late with airway obstruction and have a poor prognosis. Under 5 percent of laryngeal cancers.

Barriers to spread

The conus elasticus and the quadrangular membrane, the thyroid and cricoid cartilages, and the anterior commissure tendon of Broyles all resist tumour spread. Broyles tendon is a weak point where the perichondrium is absent, permitting anterior spread through the thyroid cartilage, which is why anterior commissure involvement upstages the tumour and reduces the success of transoral surgery and radiotherapy.

The paraglottic and pre epiglottic spaces are fat filled compartments that permit submucosal spread with a deceptively normal mucosal surface. Pre epiglottic space invasion classifies a tumour as T3 even when it appears superficially limited, and this is only detectable on imaging, which is why cross sectional imaging is required for staging even when the endoscopic appearance seems modest.

Risk factors

Tobacco and alcohol, acting synergistically, account for the great majority. Others include occupational exposure to asbestos, wood dust, nickel, sulphuric acid mist and polycyclic aromatic hydrocarbons, gastro oesophageal reflux, previous radiotherapy, human papillomavirus in a small proportion, and laryngeal papillomatosis with malignant transformation.

Glottic tumours

• Hoarseness, which appears when the tumour is only millimetres in size and which is the reason glottic cancer is curable. Any hoarseness persisting beyond 3 weeks requires laryngoscopy, and in a smoker this should be urgent.
• Progressive rather than fluctuating dysphonia.
• Later: stridor, dyspnoea, dysphagia and referred otalgia.

Supraglottic tumours

• Vague throat discomfort, a sensation of a lump, and a persistent sore throat, symptoms that are commonly attributed to reflux or pharyngitis for months.
• Referred otalgia through the internal branch of the superior laryngeal nerve to the auricular branch of the vagus, which is a highly significant symptom and which occurs with a normal ear examination.
• Odynophagia and dysphagia.
• A neck lump, which is frequently the presenting feature.
• Muffled hot potato voice rather than hoarseness, since the vocal folds are spared until late.
• Weight loss.

Subglottic tumours

• Dyspnoea and stridor as the presenting features.
• Hoarseness only when the vocal folds or recurrent laryngeal nerve are involved.

Red flags in any patient

• Hoarseness beyond 3 weeks.
• Referred otalgia with a normal ear.
• Stridor.
• Dysphagia and weight loss.
• Haemoptysis.
• A neck mass.
• Fixation of a vocal fold.
• Laryngeal crepitus loss, that is loss of the normal crackle on moving the larynx across the vertebrae, which suggests postcricoid or retrolaryngeal disease.

Examination

• Flexible nasolaryngoscopy in every case, documenting the subsite, the extent, the anterior commissure, subglottic extension, and critically the mobility of both vocal folds, since impaired mobility indicates T2 and fixation indicates T3.
• Palpate the neck systematically and record levels.
• Palpate the thyroid cartilage for tenderness and expansion, which suggests cartilage invasion.
• Assess the airway.
• Full oral and oropharyngeal examination for a second primary.
• Assess nutrition, performance status and comorbidity.

• Flexible nasolaryngoscopy with stroboscopy where available, which detects early loss of the mucosal wave indicating invasion beyond the epithelium.
• Narrow band imaging and other enhanced endoscopic techniques, which improve detection of superficial lesions and delineation of margins.
• Microlaryngoscopy under general anaesthesia with biopsy, which is essential for tissue diagnosis and for accurate mapping of the tumour, including assessment of the ventricle, subglottis, anterior commissure and the extent of vocal fold involvement. This is also the moment to assess whether transoral resection is feasible, since adequate exposure at endoscopy is a prerequisite for transoral laser surgery.
• Panendoscopy with examination of the oesophagus and tracheobronchial tree for synchronous second primaries, present in 3 to 5 percent.
• Contrast enhanced computed tomography of the neck and chest, which is the standard staging investigation. It assesses paraglottic and pre epiglottic space invasion, thyroid and cricoid cartilage erosion, subglottic extension, nodal disease and pulmonary metastases or a second primary.
• Magnetic resonance imaging, which is superior for cartilage invasion and for soft tissue extent, though it overestimates cartilage invasion because of peritumoural inflammation.
• Positron emission tomography with computed tomography for stage III and IV disease, for suspected distant metastasis, and for post treatment response assessment at 12 weeks.
• Ultrasound guided fine needle aspiration of any neck node.
• Dental assessment with orthopantomogram before radiotherapy.
• Full blood count, renal and liver function, albumin, thyroid function as a baseline, and nutritional assessment.
• Audiometry before cisplatin.
• Human papillomavirus and p16 testing where relevant, though its prognostic significance is established for the oropharynx rather than the larynx.

Staging highlights

• Glottic: T1a one fold with normal mobility, T1b both folds, T2 supraglottic or subglottic extension or impaired mobility, T3 fold fixation or paraglottic space invasion or inner cortex thyroid cartilage erosion, T4a through the outer cortex of the thyroid cartilage or into tissues beyond the larynx.
• Supraglottic: T1 one subsite with normal mobility, T2 more than one adjacent subsite, T3 fold fixation or invasion of the postcricoid, pre epiglottic space, paraglottic space or inner cortex, T4a.
• Nodal staging incorporates extranodal extension as N3b.

All cases through a head and neck multidisciplinary team. The dominant theme is organ preservation without compromising cure, and the honest recognition that a preserved but non functioning larynx with chronic aspiration is not a success.

Carcinoma in situ and severe dysplasia

• Transoral laser excision or stripping with careful preservation of the vocal ligament, or radiotherapy.
• Absolute smoking cessation.
• Intensive surveillance at 3 monthly intervals, since progression to invasive carcinoma occurs in a significant proportion.

Early glottic carcinoma, T1 and T2

Local control exceeds 90 percent for T1 with either transoral laser microsurgery or radiotherapy, and the choice rests on voice outcome, cost, convenience, and the ability to salvage.

• Transoral laser microsurgery: performed with carbon dioxide laser through a suspension laryngoscope, with cordectomy classified from type I subepithelial to type VI extended. Advantages are a single short procedure, histological margin assessment, preservation of radiotherapy for a later second primary, and lower cost. It requires adequate endoscopic exposure, which is limited by a short neck, trismus, prominent teeth and cervical spine disease, and anterior commissure involvement reduces its success.
• Radiotherapy: typically 63 to 66 Gy in 28 to 33 fractions, or hypofractionated regimens for T1 glottic disease. Advantages are a possibly better voice outcome in tumours involving the anterior commissure or the free edge, and no need for endoscopic access. Disadvantages are 5 to 6 weeks of daily treatment, the loss of radiotherapy as a future option, and late toxicity including xerostomia and hypothyroidism.
• Open partial laryngectomy, including vertical partial laryngectomy, for selected cases.
• No elective neck treatment for T1 glottic disease given the very low occult metastasis rate. Elective neck treatment for T2 with supraglottic extension.

Early supraglottic carcinoma, T1 and T2

• Transoral laser microsurgery or supraglottic laryngectomy, with elective bilateral neck dissection of levels II to IV, or radiotherapy to the primary and both necks. Elective neck treatment is mandatory given the 30 to 50 percent occult metastasis rate, and this is the key difference from glottic disease.

Locally advanced disease, T3 and T4

• Organ preservation with concurrent chemoradiotherapy: radiotherapy 70 Gy in 35 fractions with concurrent cisplatin 100 mg/m squared on days 1, 22 and 43, which achieves laryngeal preservation in around two thirds without compromising survival compared with laryngectomy in appropriately selected T3 disease. Cetuximab is an alternative in cisplatin ineligible patients but is inferior.
• Induction chemotherapy with docetaxel, cisplatin and fluorouracil followed by radiotherapy in responders and laryngectomy in non responders, used as a selection strategy in some centres.
• Open partial laryngectomy, including supracricoid partial laryngectomy with cricohyoidoepiglottopexy or cricohyoidopexy, in selected T2 and T3 tumours, which preserves speech and swallowing without a stoma but which requires good pulmonary reserve, since all patients aspirate during rehabilitation and a patient who cannot tolerate that will not succeed. Careful patient selection with attention to age, pulmonary function and motivation determines outcome.
• Total laryngectomy as primary treatment for T4a disease with cartilage destruction through the outer cortex and extralaryngeal spread, since organ preservation protocols give poorer outcomes in this group. Also for a non functioning larynx, for extensive cartilage involvement, and for tumours involving the posterior commissure and interarytenoid region.
• Total laryngectomy for salvage after failed radiotherapy or chemoradiotherapy, which is technically more difficult with higher rates of pharyngocutaneous fistula, and where a vascularised flap should be used to reinforce the pharyngeal closure.
• Neck dissection as indicated by subsite and nodal status, with bilateral dissection for supraglottic and midline tumours.
• Adjuvant radiotherapy or chemoradiotherapy after surgery for positive margins, extranodal extension, T3 and T4 disease, multiple nodes and perineural invasion.

Airway management at presentation

• A patient with stridor requires urgent assessment. Nebulised adrenaline, intravenous dexamethasone and heliox are temporising measures.
• Tracheostomy under local anaesthesia is often the safest approach in a critically obstructed larynx, avoiding the hazards of induction in an obstructed airway.
• Where possible, obtain the biopsy and complete staging before committing to a tracheostomy, since a tracheostomy through tumour risks stomal recurrence, but airway safety takes priority.
• Debulking with laser at microlaryngoscopy is an alternative in selected cases.

Total laryngectomy and rehabilitation

• The patient becomes a permanent neck breather with a stoma, with complete separation of the airway from the digestive tract. This must be explained thoroughly before consent, including the loss of nasal filtering, humidification and olfaction, and the inability to swim, blow the nose or lift heavy weights against a closed glottis.
• Voice rehabilitation:
• Tracheoesophageal puncture with a voice prosthesis, which is the gold standard, achieving fluent speech in 80 to 90 percent. Performed primarily at the time of laryngectomy or secondarily later. Requires manual dexterity or a hands free valve, regular prosthesis changes every 3 to 6 months, and management of leakage and candidal colonisation.
• Oesophageal speech, which requires no device but is difficult to learn, with fewer than half achieving fluency.
• Electrolarynx, which is immediately available and reliable, useful in the early postoperative period and as a backup.
• Heat and moisture exchange devices worn over the stoma, which restore humidification, reduce mucus production and coughing, and improve pulmonary function. These are frequently underprescribed and make a substantial difference to quality of life.
• Olfactory rehabilitation with the nasal airflow inducing manoeuvre, that is the polite yawn technique, which restores smell in a majority who are taught it.
• Swallowing rehabilitation with speech and language therapy.
• Stoma care education, and a stoma alert for emergency services, since resuscitation of a neck breather requires ventilation through the stoma and not the mouth. Ensure the patient carries identification.
• Psychological support, given the profound effect on identity, communication and appearance.

Complications of treatment

• Pharyngocutaneous fistula after laryngectomy in 10 to 30 percent, higher after salvage surgery, managed with wound care, nutrition, antibiotics and, where persistent, flap repair.
• Stomal stenosis and stomal recurrence.
• Hypothyroidism in up to 50 percent after laryngectomy with hemithyroidectomy and neck irradiation, requiring annual thyroid function testing and thyroxine replacement, which is frequently overlooked.
• Hypoparathyroidism after total laryngectomy with thyroidectomy.
• Pharyngoesophageal stricture requiring dilation.
• Chronic aspiration after partial laryngectomy.
• Osteoradionecrosis, chondroradionecrosis of the laryngeal cartilage, xerostomia, dysphagia, carotid stenosis and second malignancy after radiotherapy.
• Shoulder dysfunction after neck dissection.

Follow up

• Clinical review with flexible laryngoscopy every 1 to 2 months in year 1, 2 to 4 monthly in year 2, 4 to 6 monthly in years 3 to 5, then annually for life.
• Positron emission tomography with computed tomography at 12 weeks after chemoradiotherapy.
• Annual thyroid function testing.
• Annual chest imaging in high risk patients.
• Lifelong smoking and alcohol cessation support, since continued use drives second primaries and recurrence.
• Prompt investigation of any new hoarseness, pain, swelling or dysphagia, since salvage is possible only when recurrence is detected early.
• Post radiotherapy laryngeal oedema is common and may take months to resolve, but persistent or worsening oedema with pain requires biopsy under anaesthesia to exclude recurrence, recognising that biopsy of an irradiated larynx carries a risk of precipitating chondronecrosis.