[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Head and neck](https://durgical.com/en/general-pathology/areas/head-neck/) › Head and neck squamous cell carcinoma

# 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.

Updated Nov 12, 2026

## Key points

- HPV-negative: oral cavity (ventral tongue, floor of mouth), larynx; tobacco, alcohol, betel quid; TP53 mutations; keratinising.
- HPV-positive: oropharynx (tonsils, base of tongue); HPV-16; E6 and E7 inactivate p53 and RB; nonkeratinising, basaloid; p16 strongly positive.
- HPV tumours: small primary, large cystic neck nodes; better prognosis.
- Field cancerization: second primary tumours appear at a high yearly rate because the whole mucosa is mutagenised.
- Spread: first to cervical lymph nodes, later lung, liver and bone.
- Oral cancer in young non-smokers without HPV is rising, cause unknown.

## 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](https://durgical.com/en/conditions/head-and-neck-squamous-cell-carcinoma/) | 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.

## Memory aid

Smoke and spirits keratinise the mouth; the virus hides in the tonsil crypts.

## 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).

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## Connections

## Related 9

- [Oncogenic viruses and H. pylori: the table to know](https://durgical.com/en/general-pathology/oncogenic-viruses-and-h-pylori-the-table-to-know/)
- [Tobacco: how smoking injures tissue](https://durgical.com/en/general-pathology/tobacco-how-smoking-injures-tissue/)
- [Alcohol: how it injures the liver, brain, heart and fetus](https://durgical.com/en/general-pathology/alcohol-how-it-injures-the-liver-brain-heart-and-fetus/)
- [Tumour suppressor genes: RB, TP53, APC, BRCA and the two-hit hypothesis](https://durgical.com/en/general-pathology/tumour-suppressor-genes-rb-tp53-apc-brca-and-the-two-hit-hypothesis/)
- [Leukoplakia and erythroplakia](https://durgical.com/en/general-pathology/leukoplakia-and-erythroplakia/)
- [Laryngeal carcinoma](https://durgical.com/en/general-pathology/laryngeal-carcinoma/)
- [Nasopharyngeal carcinoma: EBV, keratinizing and nonkeratinizing types](https://durgical.com/en/general-pathology/nasopharyngeal-carcinoma-ebv-keratinizing-and-nonkeratinizing-types/)
- [Neck cysts and paraganglioma](https://durgical.com/en/general-pathology/neck-cysts-and-paraganglioma/)
- [Oesophageal squamous cell carcinoma](https://durgical.com/en/general-pathology/oesophageal-squamous-cell-carcinoma/)

## Related conditions 3

- [Head and neck squamous cell carcinoma (oral cavity and oropharynx, HPV)](https://durgical.com/en/conditions/head-and-neck-squamous-cell-carcinoma/)
- [Laryngeal cancer](https://durgical.com/en/conditions/laryngeal-cancer/)
- [Cervical lymphadenopathy](https://durgical.com/en/conditions/cervical-lymphadenopathy/)

## Microorganisms 1

- [Human papillomavirus](https://durgical.com/en/microbiology/human-papillomavirus/)

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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](https://medlineplus.gov/headandneckcancer.html) (MedlinePlus, US National Library of Medicine, 2025); [Oral Cancer](https://medlineplus.gov/oralcancer.html) (MedlinePlus, US National Library of Medicine, 2025); [Human Papillomavirus](https://www.ncbi.nlm.nih.gov/books/NBK448132/) (StatPearls (NCBI Bookshelf), 2025).

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Source: https://durgical.com/en/general-pathology/head-and-neck-squamous-cell-carcinoma/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/head-and-neck-squamous-cell-carcinoma/