What is laryngeal cancer and how common is each subsite?
Laryngeal cancer is a malignancy of the voice box. It accounts for about one-third of all head and neck cancers. The vast majority are squamous cell carcinomas (SCC); other histologies — minor salivary gland carcinoma, sarcoma (chondrosarcoma is the commonest laryngeal sarcoma), melanoma, lymphoma — are rare. Verrucous, sarcomatoid and neuroendocrine carcinomas are the uncommon squamous variants.
About 98% of laryngeal cancers arise in the supraglottis or glottis, and glottic cancers are three times more common than supraglottic cancers. Subglottic tumours make up only about 2%. The mean age at diagnosis is around 65, with a male predominance, and incidence has been falling by about 2% a year as tobacco use declines.
What are the three subsites of the larynx and why do they behave differently?
Each subsite has its own staging system, lymphatic drainage and presentation. The supraglottis runs from the tip of the epiglottis to the ventricle and includes the suprahyoid and infrahyoid epiglottis, false vocal cords, aryepiglottic folds and arytenoids. The glottis is the true vocal cords with the anterior and posterior commissures. The subglottis extends from 5 mm below the free margin of the vocal cord to the lower border of the cricoid cartilage.
| Feature | Supraglottic | Glottic | Subglottic |
|---|---|---|---|
| Relative frequency | Less common (glottic is ~3× commoner) | Most common | About 2% |
| Lymphatic supply | Rich — early nodal spread | Sparse — nodes uncommon unless tumour extends | Sparse; drains to levels IV and VI |
| Nodes at presentation | About 55% clinically positive; ~16% contralateral | Rare unless supraglottic/subglottic extension | Uncommon |
| Usual nodal levels | II, III, IV (ipsilateral level II / jugulodigastric highest risk) | — | IV and VI |
| First symptom | Pain on swallowing (hoarseness is late) | Hoarseness (early) | Late — airway symptoms |
| Prognosis | Intermediate | Best | Poor |
What causes laryngeal cancer?
Smoking is the dominant risk factor, accounting for over 70% of cases. Any smoking history raises risk; current smokers have a higher relative risk than ex-smokers, and the relative risk is higher for supraglottic than for glottic cancer. Heavy alcohol intake is also a risk factor, although its independent effect is hard to separate because it is usually combined with tobacco; the alcohol association is strongest for the supraglottis.
- Male sex — historically 4–5 times more common in men than in women.
- Long-term passive smoke exposure (odds ratio about 1.2 when lifelong exposure exceeds 20,000 hours).
- Occupational and environmental exposures — asbestos, nickel fumes, sulfuric acid mist, wood dust, Agent Orange.
- Syndromes — Fanconi anaemia, Plummer-Vinson syndrome and dyskeratosis congenita.
- Marijuana smoking may be a risk factor in younger patients.
How does laryngeal cancer present?
The usual patient is a male smoker. The presenting symptom depends on the subsite:
- Glottic: hoarseness is the commonest early symptom, from cord bulk or fixation. Pain on swallowing and referred ear pain suggest advanced disease.
- Supraglottic: pain on swallowing (odynophagia) is the commonest early symptom; hoarseness appears late and means extension to the glottis.
- Nodal metastasis: a firm, painless, often fixed neck mass.
- Late, any subsite: weight loss, dysphagia, aspiration and its sequelae, and airway compromise (stridor).
On examination the key step is seeing the tumour — by mirror or direct laryngoscopy or, most often, fibreoptic endoscopy — to judge size, extent and vocal cord mobility. Tenderness over the thyroid cartilage suggests direct cartilage involvement, and firm fullness just above the thyroid notch classically indicates pre-epiglottic space invasion. Examination alone has a high false-positive rate, so imaging is essential.
How is laryngeal cancer diagnosed and staged?
Diagnosis is tissue: biopsy of the primary lesion under direct laryngoscopy, plus fine-needle aspiration cytology for suspected nodal disease. Contrast-enhanced CT of the neck images areas laryngoscopy cannot judge — the subglottis, pre-epiglottic and paraglottic spaces, inner table of the thyroid cartilage and nodal extranodal extension. If the cancer looks advanced, contrast CT of the chest and PET/CT exclude distant disease; oesophagogastroduodenoscopy or barium swallow is added if hypopharyngeal or oesophageal invasion is suspected.
Staging follows the AJCC 8th edition. Primary tumours are staged separately for each subsite, mainly by local extent and vocal cord mobility; nodal staging uses size, number, laterality and extranodal extension. The T categories for the two common subsites:
| T | Supraglottis | Glottis |
|---|---|---|
| T1 | One subsite of the supraglottis, normal cord mobility | Limited to the cord(s), normal mobility — T1a one cord, T1b both cords |
| T2 | Invades more than one adjacent subsite of supraglottis/glottis or region outside it, without fixation | Extends to supraglottis and/or subglottis, and/or impaired cord mobility |
| T3 | Limited to larynx with cord fixation and/or invades postcricoid area, pre-epiglottic space, paraglottic space or inner cortex of thyroid cartilage | Limited to larynx with cord fixation and/or invasion of paraglottic space or inner cortex of thyroid cartilage |
| T4a | Through the outer cortex of thyroid cartilage and/or tissues beyond the larynx (trachea, strap muscles, thyroid, oesophagus) | Same, and may include cricoid cartilage |
| T4b | Invades prevertebral space, encases carotid artery or invades mediastinal structures | Same |
How is laryngeal cancer treated?
Treatment depends on stage and subsite. The basic rule: early (stage I–II) disease is treated with a single modality — radiotherapy or surgery, with comparable survival — and the choice rests on patient preference, local expertise and whether the larynx can stay functional. Advanced (stage III–IV) disease needs multimodality treatment, and chemotherapy or immunotherapy alone is never curative.
| Situation | Treatment |
|---|---|
| T1–2 N0 glottic | Radiotherapy or surgery (endoscopic laser/robotic cordectomy). Neck is not treated because lymphatics are sparse. Local control for T1 glottic is about 90–95% |
| T1–2 N0 supraglottic | Radiotherapy or larynx-sparing surgery; both necks must be addressed because of nodal risk. Local control about 80–90% |
| T3–4, larynx still functional, no cartilage erosion | Concurrent chemoradiation (cisplatin) for larynx preservation |
| T4, or T3 with cartilage invasion, or non-functional larynx | Total laryngectomy with adjuvant radiotherapy |
| Distant metastasis | Systemic therapy, largely palliative |
- Endoscopic cordectomy — usually with a CO₂ laser (transoral laser microsurgery), for T1 and selected T2 glottic tumours; tumour at the anterior commissure or crossing to the other cord recurs more often.
- Vertical partial laryngectomy — open counterpart of cordectomy for T1, T2 and selected T3 glottic cancer; now used less.
- Supraglottic (horizontal partial) laryngectomy — removes epiglottis, false cords, upper thyroid cartilage and hyoid; needs good swallowing and lung reserve because aspiration risk rises. A temporary tracheostomy is usual.
- Supracricoid laryngectomy — for T3 and selected T4 tumours that spare at least one functioning arytenoid.
- Total laryngectomy — removes all laryngeal tissue and creates a permanent tracheostoma; the patient becomes an obligate neck breather, and oral or nasal intubation is no longer possible. Salvage option after failed radiotherapy.
Radiotherapy is external beam, usually IMRT; a cumulative dose of 60 Gy or more (typically 60–66 Gy) is curative, given as one fraction daily, Monday to Friday, over about 6 weeks. Postoperative radiotherapy is indicated for pT3–4 or pN2–3 disease and high-risk features such as close margins (<5 mm), perineural or lymphovascular invasion and extranodal extension; positive margins or extranodal extension add concurrent chemotherapy.
Where does laryngeal cancer spread and what are the treatment complications?
Laryngeal cancer spreads first to the cervical lymph nodes. The commonest site of distant metastasis is the lung, followed by liver and bone. A solitary lung lesion needs biopsy, because smokers can have a second primary lung cancer, which changes treatment and prognosis.
- Radiotherapy (IMRT): xerostomia, dysphagia (can appear years later), odynophagia, neck lymphoedema, hypothyroidism, dysgeusia, mucositis and radiation dermatitis.
- Total laryngectomy: loss of natural voice and a permanent stoma; pharyngocutaneous fistula is a risk, reduced when a vascularised flap closes the neopharynx in high-risk patients (prior radiation, extended resection).
- Supraglottic laryngectomy: microaspiration is common postoperatively.
- Second primaries: the same tobacco exposure puts the rest of the aerodigestive tract at risk.
What are the common exam traps in laryngeal cancer?
- Earliest symptom: hoarseness = glottic; odynophagia/foreign-body sensation = supraglottic. Do not swap them.
- Nodes: supraglottic spreads early and often bilaterally; glottic almost never unless extended. Early glottic cancer needs no neck treatment.
- Best prognosis: glottic > supraglottic > subglottic.
- Fixed cord = T3; impaired (not fixed) mobility = T2 in the glottis.
- Treatment of T1 glottic: radiotherapy or CO₂ laser cordectomy — not total laryngectomy.
- Treatment of T4 or cartilage invasion: total laryngectomy ± adjuvant radiotherapy; chemoradiation is the larynx-preservation route for functional larynges.
- Most common distant metastasis: lung.
- Pre-epiglottic space invasion: fullness above the thyroid notch.
For related head-and-neck staging logic see nasopharyngeal tumours and tonsillitis and peritonsillar abscess; the nodal levels are mapped in triangles of the neck.