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Laryngeal Cancer

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Key points ⚡
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Laryngeal cancer\: most common head and neck malignancy, predominantly squamous cell carcinoma (SCC).
Prevelance\: accounts for 3% of all cancer cases globally.
Anatomy\: larynx divided into supraglottis (above vocal cords), glottis (at vocal cords), subglottis (below vocal cords).
Risk factors\: smoking, alcohol, age (5th-7th decade), poor oral hygiene, HPV infection.
Clinical features\: hoarseness, stridor, dysphagia, odynophagia, voice change, referred otalgia, haemoptysis, neck lump,
weight loss.
Investigations\:
Staging\: TNM classi
Management\: early-stage (transoral resection or radiotherapy), advanced-stage (chemo-radiotherapy or surgery with
adjuvant radiotherapy), total laryngectomy often required.
Complications\: airway occlusion, invasion of adjacent structures, post-operative complications (wound infection, bleeding,
airway issues, dysphagia).
Prognosis\: survival rates vary by location and stage; vocal cord cancer has a high survival rate (83% if detected early).
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Introduction

The larynx is the most common site for head and neck malignancy. Most laryngeal cancers are squamous cell
carcinomas (SCC), however other rarer malignancies can present in the larynx including papillary carcinomas, sarcomas,
and melanomas.
1
Head and neck malignancy is the eighth most common malignancy worldwide, accounting for 3% of all cancer cases.
Symptoms of head and neck malignancy can be insidious (63% of patients are diagnosed at advanced stages).
1 in 10 head and neck SCC patients will have a separate synchronous malignancy (occurrence of a second primary
malignancy).
2

Aetiology

Anatomy

The larynx is located in the anterior neck at the level of C3 to C6. It forms part of the upper aerodigestive tract, with its main
functions including phonation and protection of the lower respiratory tract (Figure 1).
Structure of the larynx
Structurally, the larynx is divided into 3 main areas\:
Supraglottis\: above the level of the vocal cords
Glottis\: at the level of the vocal cords and the
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Subglottis\: below the level of the vocal cords
The supraglottis contains the suprahyoid epiglottis, the infrahyoid epiglottis, the false cords, the aryepiglottic folds and the
arytenoids. Malignancy at this site often invades the vallecula and base of the tongue. Lymphatic involvement is common
and 55% of patients will have nodal metastases at initial presentation.
3
The glottis contains the true vocal cords only. As it is a lymphatic watershed area, nodal metastases are uncommon.
The subglottis includes everything below the level of the vocal cords.
Anatomical borders of the larynx
Anteriorly the larynx is bounded by the\:
Infrahyoid or strap muscles (sternohyoid muscle, sternothyroid muscle, thyrohyoid muscle, omohyoid muscle)
Thyroid gland
Parathyroid glands
Laterally the larynx is bounded by the\:
Common carotid artery
Internal jugular vein
Vagus nerve
Recurrent laryngeal nerve
Posteriorly the larynx is bounded by the oesophagus.
Blood supply of the larynx
Arterial blood is supplied via the superior laryngeal artery (a branch of the superior thyroid artery) and the inferior
laryngeal artery. Venous drainage is similarly via the superior and inferior laryngeal veins.
Innervation of the larynx
The main nerves supplying the larynx are the superior laryngeal nerve and the recurrent laryngeal nerve.
Superior laryngeal nerve (external branch)\:
Cricothyroid muscle
Recurrent laryngeal nerve (inferior branch)\:
Posterior cricoarytenoid muscle
Lateral cricoarytenoid muscle
Transverse and oblique arytenoid muscles
Lymphatic drainage of the larynx
The lymphatic drainage to the supraglottis is achieved via the pre-epiglottic and upper deep cervical nodes. The vocal
cords are a lymphatic watershed area which accounts for the low risk of lymphatic spread. The subglottis drains to lower
deep cervical and pretracheal nodes.
Figure 1. Anatomy of the larynx within the upper aerodigestive tract.

Pathophysiology

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Repeated exposure of head and neck mucosa to various aerosolised carcinogens (e.g. tobacco smoke) leads to acquired
genetic mutations causing a
susceptible to tumour formation.
A minimum of 4 to 6 mutations are thought to be required for progression to solid tumours.
4
The
primary malignancy) in the upper aerodigestive tract.

Risk factors

Risk factors for laryngeal cancer include\:
6,8
Smoking\: over 80% of head and neck cancers are thought to be caused by tobacco, alcohol or a combination of both.
Alcohol\: whilst alcohol is not directly carcinogenic, it is metabolised by the liver into acetaldehyde which is highly
mutagenic.
Age\: the incidence increases with age and it is most common in the 5 th th
and 7 decade of life.
Poor oral hygiene\: this has also been shown to play a contributing factor in the development of head and neck cancers.
Human papillomavirus (HPV) infection\: currently, at least 2.4% of cases of laryngeal malignancy are attributable to HPV
infection and this number is likely to rise.

Clinical features

Clinical features can vary depending on the anatomical location of laryngeal cancer.
Glottic tumours are more likely to present with hoarseness and stridor, and patients will therefore present earlier. Tumours
at other sites can be silent until they are at a more advanced stage.
Some patients will present with enlarged neck nodes only.

History

Typical symptoms of laryngeal cancer include\:
Hoarseness
Stridor
Dysphagia
Odynophagia
Voice change
Referred otalgia
Haemoptysis
Neck lump
Weight loss
Other important areas to cover in the history include\:
Past medical history (e.g. previous malignancy, gastro-oesophageal re
Smoking history
Alcohol history
Allergies
Occupation (excessive voice use e.g. professional singer)

Clinical examination

Patients presenting with features of head and neck cancer require a thorough examination of the oral cavity and a neck
lump examination. A cranial nerve examination may also be relevant if there is concern about neural impingement.
All patients will direct visualisation of the larynx, usually by
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Di

Papillomas

Papillomas are benign wart-like vocal cord lesions arising secondary to HPV infection. They present with cough,
hoarseness and can progress to stridor. Diagnosis is usually clinical using direct visualisation and later con
biopsy.

Granulomas

The vocal cords can occasionally develop small in
chronic use or in the presence of gastro-oesophageal re
and feeling of a lump in the throat.

Vocal cord polyps

Vocal cord polyps are another common cause for hoarseness in patients with excessive voice use. These are usually small
and bilateral and cause hoarseness which is typically worse at the end of the day.

Vocal cord cysts

Cysts on the vocal cords can also present with hoarseness, chronic cough and feeling of lump in the throat. Mucous
retention cysts are small, soft vocal cord lumps and develop as a result of a blocked mucus producing gland.

Investigations

Bedside investigations

Direct examination of the larynx via a
This can show vocal cord lesions as well as immobility of the vocal cords.

Imaging

Patients can either be investigated with CT or MRI of the head and neck with contrast. Positron emission tomography (PET)
is required to identify distant metastases.

Other investigations

Direct examination of the whole upper aerodigestive tract (pan-endoscopy) under a general anaesthetic is required for
comprehensive clinical assessment. This allows for biopsies to be taken and identi

Staging

Head and neck malignancies are staged according to the TNM classi
nodal metastases and M refers to distant metastases. Staging is determined as per the American Joint Committee on
Cancer system.

Management

Early-stage laryngeal cancer can be managed with either transoral resection of the primary lesion or primary
radiotherapy.
Advanced stage malignancy can be managed with organ-preserving approaches in the form of curative primary chemo-
radiotherapy.
An alternative approach in advanced stages is primary surgery and adjuvant radiotherapy. The main determinant in
deciding between the two approaches is the baseline speech and airway function on presentation.
The larynx can be removed partially in the form of a supraglottic laryngectomy or a hemilaryngectomy if disease is early
and localised. This can avoid the need for an arti
However, patients with laryngeal cancer most often require a total laryngectomy. This removes the larynx and brings the
trachea to the skin surface as a stoma. Often, a rim of hypopharynx needs to also be removed and reconstructed at the
time of procedure either by primary closure or with the aid of a skin
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Complications

If left untreated, laryngeal cancer will occlude the airway and invade adjacent structures such as the oesophagus,
trachea, nerves (recurrent laryngeal, vagus, hypoglossal, accessory) and vessels (carotid artery, internal and external jugular
veins).
Common post-operative complications following a laryngectomy include\:
Local complications\: wound infection and breakdown leading to pharyngo-cutaneous
formation
Airway issues requiring emergency treatment
Long-term dysphagia
Risk of complications is increased in patients who also undergo lymph node dissection and radiotherapy.

Prognosis

Survival rates vary depending on the cancer stage at initial diagnosis as well as the initial location of the tumour (Table 2).
Cancer of the vocal cords is the most common type of laryngeal cancer and has a survival rate of 83% if detected early.
Table 2. Survival rates in laryngeal cancer.
10
Location Survival rate
Supraglottis 46%
Local disease
61%
Regional disease
47%
Metastatic disease
30%
Glottis 76%
Local disease
83%
Regional disease
48%
Metastatic disease
42%
Subglottis 52%
Local disease
60%
Regional disease
33%
Metastatic disease
45%

References

Ciolofan MS, Vlăescu AN, Mogoantă C-A, et al. Clinical, Histological and Immunohistochemical Evaluation of Larynx Cancer.
C u r r H e a l S c i J 2017; 43\: 367–375.
Wang WL, Chang WL, Yang HB, et al. Quanti
of high-risk patients for developing synchronous cancers over upper aerodigestive tract. O r a l O n c o l 2015; 51\: 698–703.
Koroulakis A, Agarwal M. C a n c e r , L a r y n g e a l . StatPearls Publishing. Available from\: [LINK]
Almadori G, Bussu F, Cadoni G, et al. Multistep laryngeal carcinogenesis helps our understanding of the
phenomenon\: A review. E u r J C a n c e r 2004; 40\: 2383–2388.
Sasco AJ, Secretan MB, Straif K. Tobacco smoking and cancer\: A brief review of recent epidemiological evidence. In\: L u n g
C a n c e r . 2004. Epub ahead of print August 2004. DOI\: 10.1016/j.lungcan.2004.07.998.
https\://app.geekymedics.com/notebook/2635/ 5/611/14/24, 10\:58 AM Laryngeal Cancer
Osazuwa-Peters N, Boakye EA, Chen BY, et al. Association between head and neck squamous cell carcinoma survival,
smoking at diagnosis, and marital status. J A M A O t o l a r y n g o l - H e a d N e c k S u r g 2018; 144\: 43–50.
Homann N, Tillonen J, Meurman JH, et al. Increased salivary acetaldehyde levels in heavy drinkers and smokers\: a
microbiological approach to oral cavity cancer. C a r c i n o g e n e s i s 2000; 21\: 663–8.
Martel C de, Plummer M, Vignat J, et al. Worldwide burden of cancer attributable to HPV by site, country and HPV type. I n t J
C a n c e r 2017; 141\: 664–670.
Kiaris H, Ergazaki M, Segas J, et al. Detection of Epstein-Barr virus genome in squamous cell carcinomas of the larynx. I n t J
B i o l M a r k e r s 1995; 10\: 211–215.
Cancer.Net. L a r y n g e a l a n d H y p o p h a r y n g e a l C a n c e r \: S t a t i s t i c s . Available from\: [LINK]

Image references

Figure 1. OpenStax College. A n a t o m y o f N o s e-P h a r y n x-M o u t h-L a r y n x . License\: [CC-BY]. Available from\: [LINK]

Reviewer

Mr Arun Takhar
Head and Neck Fellow

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Contents

Introduction
Aetiology
Risk factors
Clinical features
Di
Investigations
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