Head and neck squamous cell carcinoma
- Lesion
Most are squamous. Tobacco and alcohol cause keratinising tumours of the mouth; HPV-16 causes tonsil and tongue-base tumours with a better outlook.
What it is
About 95% of head and neck cancers are squamous cell carcinomas arising from the mucosa of the oral cavity, pharynx and larynx. There are two diseases: the classic tobacco and alcohol-related keratinising carcinoma, often with precursor lesions and multiple primaries, and HPV-associated, nonkeratinising carcinoma of the oropharynx, which presents early with neck nodes and has better survival. Field cancerization explains the high rate of second tumours.
Structure
- Early keratinising carcinoma: raised firm pearly plaque or verrucous thickening, often on leukoplakia.
- Advanced: ulcerated mass with indurated, rolled borders.
- Keratinising SCC: invasive nests with keratin pearls, intercellular bridges, desmoplasia; grade does not predict behaviour well.
- HPV-associated: nests and lobules of basaloid nonkeratinising cells growing within lymphoid tissue of tonsillar crypts; diffuse p16; HPV DNA or mRNA by ISH or PCR.
Step by step
- Tobacco smoke and alcohol (a solvent and source of acetaldehyde) damage and mutate the whole mucosal field.
- TP53, CDKN2A, PIK3CA and NOTCH1 alterations accumulate, with dysplasia that may or may not reach full thickness before invasion.
- In the oropharynx, high-risk HPV infects basal cells of the reticulated crypt epithelium.
- Viral E6 degrades p53 and E7 inactivates RB; p16 rises as a marker of RB loss.
- The tumour invades, spreads to neck nodes and recurs or arises again elsewhere in the field.
HPV-negative vs HPV-positive head and neck SCC
| Feature | HPV-negative (classic) | HPV-positive |
|---|---|---|
| Main site | Oral cavity, larynx | Oropharynx: tonsils, base of tongue |
| Risk factors | Tobacco, alcohol | HPV-16, sexual behaviour |
| Histology | Keratinising | Nonkeratinising, basaloid |
| Marker | TP53 mutation | p16 overexpression, HPV DNA or RNA |
| Precursor seen | Leukoplakia, erythroplakia | Usually none |
| Prognosis | Worse | Better |
Markers
- p16
- HPV in situ hybridisation
- p40
Clinical notes
- Warning signs: an ulcer or patch lasting weeks, pain, dysphagia, otalgia, hoarseness, a neck mass.
- Survival is good in early classic carcinoma and poor in advanced disease; HPV-positive tumours respond better.
- HPV vaccination is expected to reduce oropharyngeal cancer as it does cervical cancer.
Test yourself
Think of the answer, then tap the question to see it.
Which immunohistochemical marker is used as a surrogate for HPV in oropharyngeal carcinoma?
Strong, diffuse p16 expression, reflecting inactivation of RB by the viral E7 protein.
What is field cancerization?
The idea that carcinogens mutate a wide area of mucosa, so multiple independent primary tumours arise over time.
Where do HPV-associated head and neck carcinomas usually arise?
In the oropharynx, in the crypt epithelium of the palatine and lingual tonsils (base of tongue).
Connections
Microorganisms1
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Head and Neck Cancer (MedlinePlus, US National Library of Medicine, 2025); Oral Cancer (MedlinePlus, US National Library of Medicine, 2025); Human Papillomavirus (StatPearls (NCBI Bookshelf), 2025).
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Representative model, for educational purposes only.