Vulvar neoplasia

Lesion

Vulvar cancer has two roads: HPV in younger women, chronic skin disease in older women. Paget disease and a gland tumour complete the list.

Updated Nov 12, 2026

Key points

HPV-associated pathway: younger patients, smokers, HPV 16; HSIL (usual VIN) with basaloid or warty carcinoma; often multifocal with cervical or vaginal lesions; p16 diffuse block.
HPV-independent pathway: older patients, lichen sclerosus background; differentiated VIN with atypia confined to the basal layer; keratinizing carcinoma; TP53 mutation.
Spread: to inguinal and femoral nodes first, then pelvic nodes; size, depth of invasion and node status set the prognosis.
Extramammary Paget disease: red, crusted, map-like plaque; large pale intraepidermal cells with mucin (PAS, CK7 positive); usually no underlying carcinoma, unlike Paget disease of the nipple.
Papillary hidradenoma: a sharply circumscribed nodule from mammary-like glands, built like a breast intraductal papilloma; benign.

What it is

Squamous cell carcinoma is by far the most common vulvar cancer and arises through two different pathways. HPV-associated tumours grow from high-grade squamous intraepithelial lesions (usual VIN) in younger women, while HPV-independent tumours arise in older women on lichen sclerosus or lichen simplex chronicus through differentiated VIN and TP53 mutation. The vulva also has mammary-like glands that give rise to papillary hidradenoma, and its epidermis can harbour the large mucin-rich cells of extramammary Paget disease.

Structure

HSIL (usual VIN): full-thickness or near full-thickness immature atypical cells, sometimes with koilocytes; leads to basaloid or warty carcinomas with little keratin.
Differentiated VIN: subtle; the surface matures, but the basal cells are atypical and the rete ridges are elongated; leads to well-differentiated keratinizing carcinoma with keratin pearls.
Invasive carcinoma: an ulcer, nodule or exophytic mass on the labia; nests of squamous cells infiltrating the dermis.
Extramammary Paget: single cells and clusters of large cells with abundant pale cytoplasm spread through the epidermis; melanoma markers are negative.
Papillary hidradenoma: tubules and papillae lined by luminal cells over a myoepithelial layer, within a well-defined nodule of the labia or interlabial folds.

Step by step

Pathway one: high-risk HPV infects the vulvar epithelium; viral E6 and E7 disable p53 and RB.
The infected epithelium becomes HSIL and, over years and with cofactors such as smoking, invades as basaloid or warty carcinoma.
Pathway two: chronic inflammation of lichen sclerosus or lichen simplex chronicus selects cells with TP53 mutation.
These cells form differentiated VIN, which progresses quickly to keratinizing squamous cell carcinoma in older women.
Both types spread first to the inguinal and femoral lymph nodes.

The two pathways to vulvar squamous cell carcinoma

Feature	HPV-associated	HPV-independent
Typical age	Younger to middle-aged	Older, postmenopausal
Precursor	HSIL (usual VIN)	Differentiated VIN
Background skin	Often multifocal HPV lesions in the lower tract	Lichen sclerosus or lichen simplex chronicus
Molecular driver	High-risk HPV E6 and E7	TP53 mutation
Carcinoma type	Basaloid or warty	Keratinizing, well differentiated
Marker pattern	p16 strong and diffuse	p53 abnormal, p16 negative

Markers

p16 (HPV-associated)
p53 (HPV-independent)
CK7 and mucin (Paget cells)
SOX10, melan-A (to exclude melanoma)

Clinical notes

Itch, a lump or an ulcer that does not heal; any persistent vulvar lesion in an older woman needs a biopsy.
Treatment is surgical with assessment of the groin nodes; recurrence is common in extramammary Paget because the cells spread beyond the visible edge.
HPV vaccination and smoking cessation reduce the HPV-associated pathway; follow-up of lichen sclerosus targets the other.

Test yourself

Think of the answer, then tap the question to see it.

What distinguishes differentiated VIN from usual VIN?

Differentiated VIN has atypia confined to the basal layer, arises on lichen sclerosus in older women and is HPV-independent; usual VIN is HPV-driven with atypia extending up the epithelium.

To which lymph nodes does vulvar carcinoma spread first?

The inguinal and femoral lymph nodes, then the pelvic nodes.

How does extramammary Paget disease of the vulva differ from Paget disease of the nipple?

Vulvar Paget is usually confined to the epidermis without an underlying carcinoma, while nipple Paget almost always comes from an underlying breast carcinoma.

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Elsewhere in DurgiPedia

Skin: epidermis layers, dermis, hypodermis

Connections

Microorganisms1

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: Vulvar Cancer Treatment (PDQ®)–Health Professional Version (National Cancer Institute, 2026); Human Papillomavirus (StatPearls (NCBI Bookshelf), 2026).

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Representative model, for educational purposes only.