History and exam

Key diagnostic factors

common

presence of risk factors

Strong risk factors include smoking and alcohol usage, GORD and bile reflux, previous radiotherapy to the neck, history of vocal fold dysplasia, black ethnicity, male sex, and family history of laryngeal cancer.

age >40 years

Risk increases with age. Most cases are diagnosed in people 55 years and older; the median age at diagnosis is 66.[4]

hoarseness

Voice changes are common in patients with laryngeal cancer of the glottis (vocal folds). Breathy, gravelly voice or aphonia for >3 weeks suggests laryngeal cancer.

Fixation of the vocal cords, indicated by disruption of the true vocal fold mucosal wave and vocal fold mechanics, may indicate local progression of disease.

Patients with long smoking histories may have a baseline degree of dysphonia that makes it difficult to note changes caused by laryngeal cancer.

dysphagia

More common in patients with supraglottic cancer, often the presenting symptom in these patients. With larger glottic tumours, dysphagia may be present.

odynophagia (painful swallowing)

More common in patients with supraglottic cancer. Odynophagia may also be present with larger glottic tumours.

cervical lymphadenopathy

Cervical metastases may present as painless, firm masses. More common in supraglottic cancer. Glottic cancer has a much lower rate of cervical metastases. Size, location, mobility, and degree of firmness indicate degree of progression of laryngeal malignancy.

supraglottic or glottic mass

Indirect laryngoscopy allows immediate evaluation for obvious lesions involving the larynx.

lesional erythroplasia, ulceration, necrosis, or bleeding

May begin as erythroplasia and evolve into ulcerated, necrotic, friable, and bulky lesions involving the true vocal folds, false vocal folds, arytenoids, epiglottis, or subglottic larynx. Seen either with mirror laryngoscopy or flexible fibre-optic laryngoscopy.

uncommon

signs of airway obstruction

Supraglottic laryngeal cancer presents significant concerns with regard to obstructed airway.

As masses grow within or around the glottis, the airway may become obstructed and cause progressive difficulty breathing. Dyspnoea may be exacerbated by speaking or while supine.

Diminished breath sounds may also indicate airway obstruction.

haemodynamic instability

May indicate catastrophic bleeding from fistula (e.g., pharyngocarotid or tracheo-innominate artery).

Other diagnostic factors

common

sore throat

Patients with laryngeal cancer often present with insidious onset of pharyngitis.

otalgia

Referred pain to the ears may be seen in laryngeal cancer, particularly in more advanced cases.

uncommon

middle ear effusion

May be seen in more advanced cases.

stridor

Airway obstruction may be seen in advanced stages of all histological types of laryngeal cancer. In the rare case of subglottic laryngeal cancer, stridor is often the first sign.

weight loss or cachexia

Weight loss is more common in advanced supraglottic cancer. Dysphagia and odynophagia (painful swallowing) may lead to significant weight loss.

Cachexia is an ominous sign of advanced disease.

general distress

Airway obstruction or disseminated disease may be apparent on initial assessment.

oral and pharyngeal masses or leukoplakia

Signs of malignant involvement may extend to the posterior pharyngeal wall, tonsillar pillars, tonsils and palate, surfaces of oral tongue, floor of mouth, and base of tongue.

loss of laryngeal crepitus

When displacing the larynx from side to side, there should be a degree of mobility and crepitus; if not, cancer may be at a more advanced stage.

parotid and thyroid growths

Palpable nodules or masses of glands of the head and neck may indicate regional metastases or advanced disease.

diminished breath sounds

May indicate airway obstruction or pneumonia, especially when aspiration is suspected.

Risk factors

strong

tobacco use

Studies have consistently reported that tobacco smokers have a greater risk than non-smokers of developing laryngeal cancer. This risk is directly proportional to the amount and duration of smoking.[12]​​

The relative risk for laryngeal cancer is >10 for smokers who have smoked for ≥40 years.[13]​ People who smoke >30 cigarettes per day have a 7-fold increased risk of laryngeal cancer, compared with never smokers.[12]​ This risk decreases after smoking cessation.[13][29]

alcohol use >8 units/day

Alcohol has been identified as an individual risk factor for laryngeal cancer.[13][15]

The relative risk of laryngeal cancer is proportional to the amount of alcohol consumed. The relative risks of laryngeal cancer are 1.38 for people who consume the equivalent of two 12 fluid-ounce (350 mL) containers of beer daily and 3.95 for eight 12 fluid-ounce (350 mL) containers (95% CI).[14]

Combined alcohol consumption and cigarette smoking have multiplicative effects on the risk of developing laryngeal cancer. Estimated relative risks range from 8.0 to >100.0.[13]

history of radiotherapy

Many cases have been reported of patients developing laryngeal cancer many years after receiving radiotherapy to the neck.[19][30]​ However, histological variability is greater with sarcoma (rather than with squamous cell carcinoma, the predominant cell type).[19]

black ethnicity

Black men are affected more commonly than white men.​[4]​​

male sex

The male-to-female incidence ratio is about 5:1.​[4]​​

vocal fold dysplasia

Vocal cord dysplasia is associated with the development of laryngeal cancer.[20][21][22]​ Previous diagnosis of vocal fold dysplasia increases the suspicion of a newly diagnosed laryngeal lesion as malignant.

weak

GORD

GORD is associated with a 2- to 3-fold increased risk of developing laryngeal cancer.[16][17]

achlorhydria

Alkaline bile reflux in patients with achlorhydria who have undergone gastrectomy may cause chronic irritation and increase the risk of pre-malignant or malignant lesions of the larynx.[18]

family history of laryngeal cancer

One case-control study reported a 3.8-fold increased risk of laryngeal cancer in people with a family history of laryngeal cancer in a first-degree relative.[23]​ Rates of chromosomal aberration and fragile site expression were higher in patients with head and neck cancer and their first-degree relatives than in a control group.[24] A mutation in the p16 tumour suppressor gene has been identified in a family with a high incidence of head and neck cancer.[25]

Agent Orange exposure

Evidence does not consistently show an increased rate of laryngeal cancer in people (e.g., veterans) who were exposed to Agent Orange.[31] Studies have been limited by small sample size and confounding factors, such as concurrent smoking and alcohol consumption.

human papillomavirus (HPV) infection

HPV infection is detected in 28% of laryngeal cancer cases, and is associated with a 5-fold increase in the risk of laryngeal squamous cell cancer.[28]​ History of HPV-related laryngeal papillomas may be a risk factor for laryngeal cancer.[30]

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