Head & Neck Cancer
A board-focused walkthrough of head and neck squamous cell carcinoma: the tobacco/alcohol, HPV, and EBV etiologic pathways with classic vignette buzzwords. It drills the next-best-step decisions (FNA for an adult neck mass, laryngoscopy for persistent hoarseness, nasopharyngoscopy for a nasopharyngeal mass) and stage-based single- vs multi-modality management the boards test.
Overview: one cancer, three pathways
Head and neck squamous cell carcinoma (HNSCC) makes up ~90% of head and neck malignancies, arising from the mucosa of the oral cavity, pharynx (naso-, oro-, hypopharynx), and larynx. Boards frame it around two dominant etiologies. The classic carcinogen pathway is driven by tobacco and alcohol, which act synergistically; these tumors carry TP53 (p53) mutations, occur in older patients, and have a worse prognosis. The viral pathway is HPV-16–driven oropharyngeal cancer (tonsil, base of tongue) in younger, often non-smoking patients, with a markedly better prognosis. A separate entity, EBV-associated nasopharyngeal carcinoma, clusters in southern China and Southeast Asia.
Because the entire mucosa shares carcinogen exposure (field cancerization), patients face a high risk of second primary tumors and need lifelong surveillance. The recurring test themes: recognize the risk-factor vignette, choose the correct next diagnostic step, and match stage to single- vs multi-modality therapy.
- Tobacco + alcohol = biggest risk; synergistic (multiplicative) for oral cavity, larynx, hypopharynx
- Smokeless tobacco / betel (areca) nut → oral cavity SCC (buccal mucosa); also oral submucous fibrosis
- HPV-16 → oropharyngeal SCC; E6 degrades p53, E7 inactivates Rb; p16 IHC = surrogate marker
- EBV → nasopharyngeal carcinoma (southern Chinese, North African); nonkeratinizing 'lymphoepithelioma'
- Plummer-Vinson: iron-deficiency anemia + esophageal web + dysphagia + glossitis → post-cricoid/hypopharyngeal SCC
- Wood dust → sinonasal adenocarcinoma; nickel refining → sinonasal SCC
- Referred otalgia (ear pain, normal ear exam) → occult pharyngeal/laryngeal tumor via CN IX/X
- Erythroplakia > leukoplakia for malignant potential (red = more dangerous)
- Glottic (true cord) cancer → early hoarseness, sparse lymphatics = good prognosis
- Supraglottic/hypopharyngeal → present late with nodal spread = worse prognosis
HPV-positive vs HPV-negative oropharyngeal SCC
| Feature | HPV-positive | HPV-negative (tobacco/alcohol) |
|---|---|---|
| Typical site | Oropharynx (tonsil, base of tongue) | Oral cavity, larynx, hypopharynx |
| Patient | Younger, non-/light smoker | Older, heavy smoker + drinker |
| Molecular | E6→p53↓, E7→Rb↓; p16 positive | TP53 mutation; p16 negative |
| Node presentation | Cystic cervical node | Solid node, less often cystic |
| Prognosis | Better (radiosensitive) | Worse |
Stem: A 62-year-old man with a 40-pack-year history and heavy alcohol use has 6 weeks of progressive hoarseness. Flexible laryngoscopy shows an irregular lesion on the right true vocal cord; no palpable neck nodes.
Diagnosis: glottic squamous cell carcinoma. Hoarseness persisting >2–3 weeks, especially in a smoker, mandates laryngoscopy — never write it off as laryngitis.
Next step: biopsy the lesion at laryngoscopy to confirm SCC; stage with contrast CT neck + CT chest (± PET-CT).
Management: early glottic cancer (T1–T2, N0) is cured by a single modality — radiation OR transoral/laser surgery — with excellent voice preservation. The true cords' poor lymphatic drainage explains early symptoms and late nodal spread. Advanced disease → concurrent chemoradiation (cisplatin) ± surgery.
Stem: A 55-year-old man has a painless, firm 3-cm mass at the upper jugular chain for 2 months, no fever or recent infection. Oropharyngeal exam looks unremarkable.
Next best step: fine-needle aspiration (FNA) of the node — the correct first test for an adult neck mass. Do NOT perform open/excisional biopsy first (risks tumor seeding, violates fascial planes, and worsens outcomes if it is SCC).
Then: if FNA shows SCC, find and biopsy the likely primary (tonsil/base of tongue) via exam + panendoscopy; get contrast CT/MRI and PET-CT; test tissue for p16/HPV.
Diagnosis: metastatic HPV-associated oropharyngeal SCC — the classic cause of a cystic cervical node in a middle-aged adult. A 'branchial cleft cyst' appearing de novo in an adult is metastatic SCC until excluded.
Stem: A 45-year-old man from southern China has unilateral nasal obstruction and epistaxis plus new unilateral serous otitis media (conductive hearing loss), a firm posterior cervical node, and diplopia.
Key clue: unilateral serous otitis media in an adult = obstruction of the Eustachian tube by a nasopharyngeal mass until proven otherwise; cranial-nerve palsies signal skull-base extension.
Diagnosis: EBV-associated nasopharyngeal carcinoma (nonkeratinizing/undifferentiated 'lymphoepithelioma').
Next step: nasopharyngoscopy with biopsy; MRI skull base; PET-CT for staging.
Management: the tumor is highly radiosensitive and anatomically hard to resect → definitive (chemo)radiation, not primary surgery; add cisplatin-based chemotherapy for advanced/nodal disease.
Premalignant mucosal lesions
- Leukoplakia: white plaque that cannot be scraped off (vs candidal pseudomembrane, which wipes off) → biopsy to grade dysplasia
- Erythroplakia: red velvety patch; much higher rate of dysplasia/carcinoma → biopsy any persistent lesion
Diagnosis — next best steps
- Suspicious oral/mucosal lesion → incisional/punch biopsy
- Adult neck mass → FNA (not excisional biopsy)
- Hoarseness >2–3 wk in a smoker → laryngoscopy
- Staging: contrast CT/MRI of primary + neck, CT chest, and PET-CT
Management principles
- Early (I–II): single modality — surgery OR radiation
- Advanced (III–IV): multimodality — surgery + adjuvant RT, or concurrent chemoradiation (cisplatin); cetuximab (anti-EGFR) is an option
- Nasopharynx: (chemo)radiation, not surgery
- Lifelong surveillance for recurrence and second primaries; counsel tobacco/alcohol cessation
A classic ENT teaching heuristic (the 'rule of 80s') for a persistent neck mass in an adult (nonthyroid):
- ~80% are neoplastic
- Of those, ~80% are malignant
- Of the malignant ones, ~80% are metastatic (not a primary node cancer)
- And ~80% of those metastases are squamous cell carcinoma from a head-and-neck mucosal primary
Takeaway: treat a persistent adult neck mass as cancer until proven otherwise — image it, do FNA, hunt for the mucosal primary, and avoid up-front excisional biopsy. (These are memory approximations, not precise statistics.)
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