Head and neck squamous cell carcinoma
Head and neck squamous cell carcinoma arises from the mucosal epithelium of the oral cavity, pharynx, and larynx along two pathways, tobacco/alcohol-driven and HPV-16-driven oropharyngeal disease, presenting with site-specific symptoms culminating in a new neck mass. Diagnosis requires laryngoscopy and biopsy of the primary with p16 testing, and treatment is single-modality surgery or radiation for early stage, cisplatin-based chemoradiation for locally advanced disease, and checkpoint inhibitors or cetuximab for recurrent or metastatic disease.
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What this article covers
- Overview
Definition: head and neck squamous cell carcinoma (HNSCC) arises from the mucosal epithelium of the oral cavity, pharynx, and larynx, the most common histology of head and neck cancer.
- Epidemiology
Sex predominance: males have a 3 to 6 times higher prevalence than females.
- Risk factors
Smoked and smokeless tobacco use: the single most important risk factor for HNSCC.
- Pathophysiology
Field cancerization from chronic carcinogen exposure: tobacco smoke and alcohol metabolites bathe the aerodigestive mucosa, producing widespread epithelial damage that predisposes to multiple…
- Clinical features
New neck mass: painless, firm, and/or fixed without antecedent infection, the hallmark of nodal metastasis and most common presenting sign; in HPV-related oropharyngeal cancer it is often cystic on…
- Differential diagnosis
Reactive lymphadenopathy: a tender node with fever, fatigue, or pharyngitis, rapidly enlarging with warmth, tenderness, or erythema, unlike the painless fixed node of malignancy.
- Diagnosis
Diagnosis is established by biopsy of the primary lesion or a suspicious neck node, confirming squamous histology; p16 immunostaining, a surrogate for HPV-driven biology, is standard for oropharynx…
- Management
Determine extent of disease first, then choose single-modality versus multimodality therapy by stage: about one third of patients present with a small tumor and no nodal metastases, effectively…
- Complications
Locoregional invasion: extension into cranial nerves, cartilage, bone, or vessels causes loss of voice/swallowing/airway function, pain, and carotid blowout hemorrhage.
- Prognosis
Stage is the most important determinant of prognosis; early-stage disease has 70% to 90% long-term survival.
- Prevention
Tobacco cessation: counsel every smoker/smokeless tobacco user to quit, the most important modifiable risk factor; continued use drives second primaries (smoking cessation).
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