Laryngeal Cancer: Causes, Symptoms, Diagnosis and Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Laryngeal cancer is a squamous cell carcinoma (SCC in over 95% of cases) arising from the mucosa lining the larynx — the voice box responsible for phonation, airway protection during swallowing, and respiration. The larynx is anatomically divided into three regions: the glottis (true vocal cords and anterior/posterior commissures, most common subsite, 60-65%), the supraglottis (epiglottis, aryepiglottic folds, false cords, 30-35%), and the subglottis (below the vocal cords, rarest, 5%). Approximately 12,500 new US cases are diagnosed annually. Tobacco smoking is the dominant etiological factor, with alcohol acting as a synergistic co-carcinogen. Glottic cancers cause early hoarseness, enabling diagnosis at an early stage when cure rates exceed 90%. Supraglottic cancers lack early symptoms, presenting with advanced neck nodal disease in a higher proportion of patients. Since the landmark Department of Veterans Affairs Larynx Study (1991) and RTOG 91-11 (2003), larynx-preservation chemoradiation has become the standard of care for resectable Stage III-IV disease.

Cigarette smoking is the primary etiological factor for laryngeal SCC, responsible for approximately 85% of cases; the risk scales with pack-year exposure and is compounded by heavy alcohol consumption, which acts synergistically to increase risk by up to 30-fold compared to non-users of either substance. The combined carcinogen exposure acts on the glottic mucosa through direct contact and inspired volatile compounds. The duration of tobacco abstinence reduces laryngeal cancer risk progressively, reaching near non-smoker levels after 15-20 years of cessation. Human papillomavirus (HPV), primarily HPV-16, contributes to a minority of laryngeal SCCs (approximately 10-15%), particularly supraglottic lesions, though the HPV-attributable fraction is far lower than for oropharyngeal cancer. Occupational exposures associated with elevated risk include asbestos, wood dust, paint fumes, and textile fiber dust. Gastroesophageal reflux with laryngopharyngeal reflux has been suggested as a risk factor, though the causal relationship remains debated. Male sex (4:1 male predominance) and age 50-70 years are consistent demographic risk factors.

Hoarseness (dysphonia) is the hallmark presenting symptom of glottic laryngeal cancer, occurring early because even small vocal cord lesions disrupt the mucosal wave. Hoarseness persisting beyond 3 weeks in a current or former smoker mandates laryngoscopy. Supraglottic cancers may be clinically silent in the early stages and present with dysphagia, odynophagia, muffled voice (hot-potato voice), or a painless neck mass from cervical nodal metastasis, without hoarseness until the tumor involves the true vocal cords. Referred otalgia (ear pain from vagal nerve irritation) is characteristic of hypopharyngeal or supraglottic tumors. Advanced glottic or subglottic cancer causes stridor (inspiratory or biphasic) from airway narrowing, potentially progressing to complete airway obstruction requiring emergency tracheotomy. Weight loss, aspiration, coughing after swallowing, and progressive breathlessness indicate locally advanced disease. Fixed vocal cord mobility on laryngoscopy signifies T3 or T4 disease and mandates cross-sectional imaging.

Flexible nasopharyngolaryngoscopy (NPL) in the outpatient clinic is the initial examination, providing real-time assessment of vocal cord mobility, tumor extent, and mucosal involvement. Microlaryngoscopy under general anesthesia with biopsy of the primary tumor and examination of the entire upper aerodigestive tract (panendoscopy) is required for definitive histological diagnosis and mapping of tumor extent including subglottic extension. CT of the neck and chest with intravenous contrast is the primary staging modality, assessing cartilage involvement (thyroid, cricoid, arytenoid), pre-epiglottic and paraglottic space invasion, cervical nodal disease, and distant metastases. MRI of the larynx is superior to CT for detecting early marrow invasion of cartilage (T4a criteria) and soft tissue spread. PET-CT identifies occult nodal disease and distant metastases. AJCC 8th edition TNM staging: T1 (limited to one laryngeal subsite, normal mobility), T2 (extension within larynx, impaired mobility), T3 (cord fixation or invasion of paraglottic space/minor thyroid cartilage), T4a (moderately advanced: outer thyroid cartilage, cricoid, strap muscles, thyroid gland, trachea), T4b (very advanced: prevertebral space, mediastinal structures, carotid artery).

T1a glottic cancer (one vocal cord, normal mobility): transoral laser microsurgery (TLM; endoscopic CO2 laser cordectomy) or radiation therapy (66 Gy over 6.5 weeks) — both achieve local control exceeding 90% and excellent voice outcomes. T1b-T2 glottic: radiation preferred for voice quality; TLM or partial laryngectomy if radiation contraindicated. T2-T3 glottic and supraglottic: concurrent chemoradiation with cisplatin 100 mg/m2 every 3 weeks plus 70 Gy is the preferred larynx-preservation strategy based on RTOG 91-11 (larynx preservation 88% at 2 years, superior to induction cisplatin-5FU followed by radiation). T4a disease: total laryngectomy plus bilateral selective neck dissection plus postoperative chemoradiation (60-66 Gy plus cisplatin) if margins positive or extranodal extension present. Transoral robotic surgery (TORS) for select supraglottic T1-T2 tumors. Cetuximab plus radiation is an alternative for cisplatin-ineligible early elderly patients. For recurrent or metastatic disease, pembrolizumab plus platinum-5FU or pembrolizumab monotherapy (PD-L1 CPS greater than or equal to 1) is first-line per KEYNOTE-048.

Five-year overall survival by stage: T1 glottic: 90-95%; T2: 70-80%; T3: 50-70%; T4a: 40-55%; Stage IV with distant metastases: less than 20%. Glottic cancers have better prognosis than supraglottic cancers of equivalent T stage due to earlier symptom onset enabling earlier diagnosis. Complete metabolic response on post-treatment PET-CT (obtained 12 weeks after chemoradiation, Deauville score 1-2) predicts an excellent outcome and may avoid planned salvage neck dissection. Locoregional recurrence occurs in 30-40% of T3-T4 cases and often requires salvage laryngectomy, which is technically challenging but achievable with good voice rehabilitation outcomes. The prognosis for Laryngeal Cancer: Causes, Symptoms, Diagnosis and Treatment varies depending on severity at diagnosis, the patient's overall health, and how promptly treatment is initiated. With early diagnosis and appropriate management, many patients achieve good outcomes and maintain quality of life. Regular follow-up with healthcare providers is essential to monitor progress, adjust treatment as needed, and detect any complications early. Adherence to prescribed treatments and lifestyle modifications significantly improves long-term prognosis.

Tobacco smoking cessation is the highest-impact preventive measure, with risk reduction of approximately 50% within 5 years of quitting and greater than 80% after 15-20 years. Combined tobacco and alcohol cessation eliminates the dominant synergistic carcinogen exposure responsible for the vast majority of laryngeal cancers. HPV vaccination (Gardasil 9) in adolescents and young adults may reduce HPV-attributable laryngeal and oropharyngeal cancer risk in future decades. Respiratory protection against known occupational carcinogens (asbestos, paint fumes, wood dust) reduces occupational laryngeal cancer risk. There is no established population-based laryngeal cancer screening program. Clinician awareness is the key: any current or former smoker presenting with hoarseness exceeding 3 weeks should be referred for laryngoscopy without delay, as early glottic cancer is highly curable and larynx-preserving treatment avoids permanent stoma.

Any hoarseness lasting more than 3 weeks in a current or former smoker requires immediate referral to an ENT specialist for laryngoscopy — do not attribute persistent hoarseness to a 'smoker's voice' without formal examination. Stridor (a high-pitched noise during breathing) combined with progressive shortness of breath is a potential airway emergency requiring same-day emergency evaluation. A painless, progressive neck lump in an adult over 40 who smokes requires urgent ENT evaluation and fine-needle aspiration biopsy, even without throat symptoms, as it may represent a supraglottic cancer with regional metastasis as the first presentation. Referred ear pain (otalgia) without ear disease, difficulty swallowing (dysphagia), or unexplained weight loss combined with any throat symptoms warrants prompt evaluation. Anyone who has completed treatment for laryngeal cancer and develops new-onset hoarseness, pain, difficulty swallowing, or neck swelling between scheduled surveillance appointments should contact their oncology team immediately for evaluation of disease recurrence.