Laryngeal cancer

See also the separate Head and Neck Cancers article.

What is laryngeal cancer?

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

How common is laryngeal cancer? (Epidemiology)¹

• Cancer of the larynx is the second most common form of head and neck cancer.

• Around 2,400 people were diagnosed with laryngeal cancer in the UK in 2021 (incidence 2.9 per 100,000 people).²

• Laryngeal cancer is more than four times more common in men than in women.

• Laryngeal cancer incidence rates in men rose until the early 1990s and have steadily fallen since then.

• Current incidence rates in men are lower than in the mid-1970s. Laryngeal cancer incidence rates in women rose until the late 1980s and have steadily fallen since then.

• Current incidence rates in women are similar to those in the mid-1970s.

• Laryngeal cancer is rarely diagnosed in people aged under 40. Nearly three quarters of cases present in people aged 60 and over.

• Incidence rates vary around the world.

Risk factors²

• Smoking is the main avoidable risk factor for laryngeal cancer, linked to an estimated 79% of laryngeal cancer cases in the UK. An estimated 93% of laryngeal cancers in the UK are linked to lifestyle factors, including smoking, and alcohol (25%).

• Certain occupational exposures (asbestos, formaldehyde, nickel, isopropyl alcohol and sulphuric acid mist) can also cause laryngeal cancer.

• A diet high in fruit and vegetables may protect against laryngeal cancer. Insufficient fruit and vegetables intake is linked to an estimated 45% of laryngeal cancer cases in the UK.

• Environmental tobacco smoke may be associated with higher laryngeal cancer risk but the evidence is unclear.

• Human papillomavirus type 16 (HPV16) seropositivity is associated with an increased risk of oral, pharyngeal and laryngeal cancer.³

Presentation of laryngeal cancer⁴

• Chronic hoarseness is the most common early symptom.

• Other symptoms of laryngeal cancer include pain, dysphagia, a lump in the neck, sore throat, earache or a persistent cough.

• Patients may also describe breathlessness, aspiration, haemoptysis, fatigue and weakness, or weight loss.

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.

Differential diagnosis¹

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

Investigations⁶

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

• Refer urgently for CXR patients with hoarseness persisting for more than three weeks, particularly smokers aged older than 50 years and heavy drinkers:
  

  • If there is an abnormality on the CXR, refer urgently to a team specialising in the management of lung cancer.

  • Otherwise, if the CXR is normal, refer urgently to a team specialising in head and neck cancer.

• 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.

• Fine-needle aspiration (FNA) of a neck mass.

• Investigations to assess the diagnosis and for staging include CT and/or MRI scans.⁷ Other investigations include CXR, pulmonary function tests and positron emission tomography-computerised tomography (PET-CT) scan.

• Examination under general anaesthesia allows palpation and direct laryngoscopy with biopsy.

Staging²

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).

• 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).

• 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).

• 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 Head and Neck Cancers article.

Referral

NICE recommends an urgent referral for patients with possible laryngeal cancer as follows:⁵

Consider a suspected cancer pathway referral (for an appointment within two weeks) for laryngeal cancer in people aged 45 and over with:

• Persistent unexplained hoarseness; or

• An unexplained lump in the neck.

Management of laryngeal cancer¹

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.⁸ There is currently only very limited evidence comparing open surgery and radiotherapy.^{9 10 11}

• 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.

  • Management is now focused on preservation of the larynx whenever possible but total laryngectomy may be required for advanced laryngeal cancer which is not suitable for conservative techniques or if conservative management has been unsuccessful.¹²

• Early glottic cancer:¹³
  

  • 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:
  

  • 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 one side.

• Locally advanced resectable laryngeal cancer:
  

  • 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.^{14 15}

  • 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 one 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 of laryngeal cancer

• Dysphagia, malnutrition.

• Loss of voice (and subsequent psychological distress).¹⁶

• Tracheo-innominate artery fistula and pharyngocarotid artery fistula.

• Loss of taste - potentially aggravating inadequate nutrition.

• Complications of surgery - eg, postoperative pharyngocutaneous fistula.¹⁷

• Complications of chemotherapy - eg, immunosuppression.

• Complications of radiotherapy - eg, local fibrosis and scarring, oesophageal stricture, dry mouth.

Prognosis²

• Overall, 7 in 10 men with laryngeal cancer survive the disease for five years or more. More than 6 in 10 men diagnosed with laryngeal cancer will survive the disease for ten years or more.

• Survival for laryngeal cancer is highest in younger men. More than three quarters of men diagnosed aged 15-49 survive their disease for at least five years.

• The outcome for laryngeal carcinoma depends on the initial staging. The outcomes in early disease are quite good, approaching over 90% five-year survival rates.

• For advanced disease, the five-year survival rates vary depending on the treatment modality. The five-year survival rate after concurrent chemoradiation therapy is 54%. The five-year survival rate after endoscopic laser laryngeal surgery is 55%.

• Glottic cancer has the most favourable prognosis of all forms of laryngeal cancer, as people tend to seek medical advice for chronic hoarseness.

Prevention of laryngeal cancer

• Smoking cessation.

• Moderating alcohol intake.

• Avoidance of other risk factors as mentioned above.