See also the separate article Cancers of the Head and Neck.

Virtually all cancers of the larynx are squamous cell carcinomas (SCCs). Laryngeal cancer includes tumours of the supraglottis, glottis or subglottis.¹ Within the larynx, the glottis is most frequently affected.²

Epidemiology

• In 2007, the UK incidence (per 100,000 population) was 3.0 (males 5.3; females 0.9).³
• Cancer of the larynx is the second most common form of head and neck cancer. It is the 14th most common cancer in men but is much rarer among women.² Men are affected 4-5 times more often than women.⁴
• Laryngeal cancer has a peak incidence of presentation in those aged in their 50s and 60s.⁴

Risk factors²

• Heavy smoking, heavy alcohol consumption (the two act synergistically) and poor dentition are the principle risk factors for head and neck cancers in western countries.⁵
• Human papillomavirus (HPV) 16 seropositivity is associated with an increased risk of oral, pharyngeal and laryngeal cancer.⁶
• Occupational exposure to asbestos, formaldehyde, nickel, isopropyl alcohol and sulphuric acid mist have been linked with laryngeal cancer.
• Exposure to diesel fumes is also associated with increased risk.

Presentation

• Chronic hoarseness is the most common early symptom.²
• Other symptoms of laryngeal cancer include pain, dysphagia, a lump in the neck, sore throat, earache or a persistent cough.²
• Patients may also describe breathlessness, aspiration, haemoptysis, fatigue and weakness, or weight loss.⁷

Examination

• Head and neck examination includes inspection and palpation of the oral cavity and oropharynx to rule out second primary tumours or other lesions, as well as evaluation of dentition.
• Palpation of the neck looking for enlarged lymph nodes is essential. Thorough evaluation of the cranial nerves should also be included in the physical examination.⁷

Differential diagnosis

Other diagnoses that need to be considered include other causes of persistent hoarseness, sore throat, earache or cough, depending on the presentation.

Investigations⁷

With the exception of persistent hoarseness (urgent chest X-ray to decide where to refer), investigations are not recommended in primary care as they can delay referral.⁸

• Refer urgently for chest X-ray patients with hoarseness persisting for more than 3 weeks, particularly smokers aged older than 50 years and heavy drinkers:
  • If there is an abnormality on the chest X-ray, refer urgently to a team specialising in the management of lung cancer.
  • Otherwise, if the chest X-ray is normal, refer urgently to a team specialising in head and neck cancer.⁸
• Flexible laryngoscopy is the best way to inspect the larynx, allowing evaluation of the function and anatomy of the entire larynx. Evaluation of vocal cord motility and the location and extension of the tumour are essential to stage the patient accurately.⁷
• Fine-needle aspiration (FNA) of a neck mass.
• Investigations to assess the diagnosis and for staging include CT and/or MRI scans, chest X-ray, pulmonary function tests and positron emission tomography-computerised tomography (PET-CT) scan.
• Examination under general anaesthesia allows palpation and direct laryngoscopy with biopsy.

Staging¹

The 'tumour, nodes, metastases' (TNM) staging system is used for staging head and neck cancers. T is the extent of the primary tumour; N is the involvement of regional lymph nodes; M is the presence of metastases. The depth of infiltration is predictive of prognosis.

T - primary tumour

Supraglottis

• TX - primary tumour cannot be assessed.
• T0 - no evidence of primary tumour.
• Tis - pre-invasive cancer (carcinoma in situ).
• T0 - no evidence of primary tumour.
• T1 - one subsite, normal mobility.
• T2 - mucosa of more than one adjacent subsite of supraglottis or glottis or adjacent region outside the supraglottis; without fixation.
• T3 - cord fixation or invades postcricoid area, pre-epiglottic tissues, paraglottic space, thyroid cartilage erosion.
• T4a - through thyroid cartilage; trachea, soft tissues of neck: deep/extrinsic muscle of tongue, strap muscles, thyroid, oesophagus.
• T4b - prevertebral space, mediastinal structures, carotid artery.

Glottis

• TX - primary tumour cannot be assessed.
• T0 - no evidence of primary tumour.
• Tis - pre-invasive cancer (carcinoma in situ).
• T0 - no evidence of primary tumour.
• T1 - limited to vocal cord(s), normal mobility:
  • T1a - one cord.
  • T1b - both cords.
• T2 - supraglottis, subglottis, impaired cord mobility.
• T3 - cord fixation, paraglottic space, thyroid cartilage erosion.
• T4a - through thyroid cartilage; trachea, soft tissues of neck: deep/extrinsic muscle of tongue, strap muscles, thyroid, oesophagus.
• T4b - prevertebral space, mediastinal structures, carotid artery.

Subglottis

• TX - primary tumour cannot be assessed.
• T0 - no evidence of primary tumour.
• Tis - pre-invasive cancer (carcinoma in situ).
• T0 - no evidence of primary tumour.
• T1 - limited to subglottis.
• T2 - extends to vocal cord(s) with normal/impaired mobility.
• T3 - cord fixation.
• T4a - through cricoid or thyroid cartilage; trachea, soft tissues of neck: deep/extrinsic muscle of tongue, strap muscles, thyroid, oesophagus.
• T4b - prevertebral space, mediastinal structures, carotid artery.

The N and M staging definitions are the same for all areas of the upper aerodigestive tract (UAT) and are outlined in the separate Cancers of the Head and Neck article.

Management

Total and partial laryngectomy are the main surgical procedures to treat malignant tumours of the larynx. However, organ preservation treatments using concurrent chemoradiation therapy with preservation of the larynx have shown survival rates similar to total laryngectomy plus radiation therapy.⁷

• Surgery:
  • Transoral laser microsurgery is ideal for the treatment of early-intermediate glottic and supraglottic cancer.
  • Open partial laryngectomy (resection of the vocal fold, thyroid cartilage, and paraglottic space) is an important option for more advanced tumours.
  • Total laryngectomy must be considered in cases of bulky or advanced disease, clear cartilage invasion, and failures of larynx-sparing strategies.
• Early glottic cancer:¹
  • Patients with early glottic cancer may be treated either by external beam radiotherapy or conservation surgery (either endoscopic laser excision or partial laryngectomy).
  • Prophylactic treatment of the neck nodes is not required.
• Early supraglottic cancer:¹
  • Patients with early supraglottic cancer may be treated by either external beam radiotherapy or conservation surgery.
  • Radiotherapy for patients with early supraglottic cancer should include prophylactic bilateral treatment of lymph nodes in the neck.
  • Endoscopic laser excision or supraglottic laryngectomy with selective neck dissection of lymph nodes should be considered.
  • Neck dissection should be bilateral if the tumour is not well localised to 1 side.
• Locally advanced resectable laryngeal cancer:¹
  • Patients with locally advanced resectable laryngeal cancer should be treated by total laryngectomy with or without postoperative radiotherapy, or an initial organ preservation strategy reserving surgery for salvage.
  • Treatment for organ preservation or nonresectable disease should be concurrent chemoradiation with single-agent cisplatin.
  • In patients medically unsuitable for chemotherapy, concurrent administration of cetuximab with radiotherapy should be considered.
  • Radiotherapy should only be used as a single modality when comorbidity precludes the use of concurrent chemotherapy, cetuximab or surgery.
  • Patients with T4 tumours extending through cartilage into soft tissue may be best treated by total laryngectomy with postoperative radiotherapy.
  • In patients with clinically N0 disease, treatment should be surgery (selective neck dissection) and external beam radiotherapy. If the tumour is not well localised to 1 side then both sides of the neck should be treated.
  • Patients with a clinically node-positive neck should be treated by modified radical neck dissection, with postoperative chemoradiotherapy or radiotherapy when indicated, or chemoradiotherapy followed by neck dissection.

Complications

• Dysphagia, malnutrition.
• Loss of voice.
• Tracheo-innominate artery fistula and pharyngocarotid artery fistula.
• Loss of taste - potentially aggravating inadequate nutrition.
• Complications of surgery, e.g. postoperative pharyngocutaneous fistula.
• Complications of chemotherapy, e.g. immunosuppression.
• Complications of radiotherapy, e.g. local fibrosis and scarring, oesophageal stricture, dry mouth.

Prognosis

• Survival rates are better than for oral or pharyngeal cancer, with nearly two-thirds of patients surviving for five years.²
• The outcome for laryngeal carcinoma depends on the initial staging. The outcomes in early disease are quite good, approaching over 90% 5-year survival rates.⁷
• For advanced disease, the 5-year survival rates vary depending on the treatment modality. The 5-year survival rate after concurrent chemoradiation therapy is 54%. The 5-year survival rate after endoscopic laser laryngeal surgery is 55%.⁷
• Glottic cancer has the most favourable prognosis of all forms of laryngeal cancer, as people tend to seek medical advice for chronic hoarseness.²

Prevention

• Smoking cessation.
• Moderating alcohol intake.
• Avoidance of other risk factors as mentioned above.

Document references

1. Diagnosis and management of head and neck cancer, Scottish Intercollegiate Guidelines Network (SIGN), 2006
2. Improving outcomes in head and neck cancers, NICE (2004)
3. Oral cancer - UK incidence statistics, Cancer Research UK
4. Campbell WJ et al; Head and Neck Cancer - Squamous Cell Carcinoma, eMedicine, Dec 2010
5. Graham S, Dayal H, Rohrer T, et al; Dentition, diet, tobacco, and alcohol in the epidemiology of oral cancer. J Natl Cancer Inst. 1977 Dec;59(6):1611-8. [abstract]
6. Kim L, King T, Agulnik M; Head and neck cancer: changing epidemiology and public health implications. Oncology (Williston Park). 2010 Sep;24(10):915-9, 924. [abstract]
7. Johnson JT et al; Malignant Tumors of the Larynx, eMedicine, Jan 2009
8. Referral for suspected cancer, NICE Clinical Guideline (2005)

Acknowledgements