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vulvar intraepithelial neoplasia

Monday 17 December 2012



Definition: Vulvar intraepithelial neoplasia (VIN) refers to particular changes that can occur in the skin that covers the vulva. VIN is an intraepithelial neoplasia, and can disappear without treatment. VINs are benign but if the changes become more severe, there is a chance of cancer developing after many years, and so it is referred to as a precancerous condition.


- usual vulvar intraepithelial neoplasia p16+
- differentiated vulvar intraepithelial neoplasia p16-


- Vulvar intraepithelial neoplasia (VIN) and vulvar SCC

Vulvar intraepithelial neoplasia (VIN) is classified into 2 clinicopathologic subtypes:

- usual differentiated vulvar intraepithelial neoplasia p16+

  • "usual type" or "classic type", related to human papillomavirus (HPV) infection and affecting relatively young women
  • The usual type includes warty type, basaloid type and mixed (warty and basaloid) type.
  • The usual type is HPV associated - it is positive for p16, negative or has low indices for p53, and MIB-1 is strongly positive above the basal layer.
  • VIN, usual type (including the sub-categories warty type and basaloid type) are associated with HPV.
  • They are HPV and p16 positive, negative for p53, and MIB-1 is strongly positive above the basal layer.
  • Usual VIN (warty and basaloid types): Premenopausal, HPV positive, p16 positive, low / negative p53, MIB-1 suprabasal.

- differentiated vulvar intraepithelial neoplasia p16-

  • "simplex" or "differentiated type", negative for HPV and affecting elderly women.
  • Premenopausal women are more likely to get usual type VIN, associated with HPV.
  • Postmenopausal women are more likely to get differentiated (aka simplex) type VIN, associated with vulvar dermatoses.
  • VIN, differentiated type is associated with vulvar dermatoses such as lichen sclerosus, and is HPV negative, p16 (INK4A) negative.
  • It tends to have high p53 indices, and MIB-1 expression is more confined to the basal layer.
  • Differentiated (simplex) VIN: Postmenopausal, vulvar dermatoses, HPV negative and p16 negative, high p53, MIB-1 basally.


HPV types 6 and 11 are associated with a high risk of developing papillomas, but not a high risk of progression to carcinoma. More common HPV types that confer a high risk of carcinoma include 16, 18, 31, 33 and 45.


Vulvar squamous cell carcinoma (VSCC) accounts for >90% of the malignant tumours of the vulva. Most VSCCs originate in vulvar intraepithelial neoplasia (VIN), that precede the development of VSCC by a variable period of time.

Strong evidence has accumulated showing that there are two different aetiopathogenic pathways for the development of VSCC and VIN, one associated with infection by human papillomavirus (HPV), and a second independent of HPV infection.

These two different types of VSCC have different epidemiological, pathological and clinical characteristics, and should therefore be considered as two separate entities.

Histologically, HPV-associated VSCCs are of the basaloid or warty type, and arise from VIN of the usual type.

Inactivation of p53 and the retinoblastoma tumour suppressor gene product by the viral gene products E6 and E7 is involved in the process of malignant transformation.

HPV-independent VSCCs are histologically keratinizing, are associated with differentiated VIN and lichen sclerosus, and frequently show mutations of p53. p16(INK4a) and p53 immunostaining can be useful for classifying VSCC into HPV-associated or HPV-independent.


- superficially invasive SCC of the vulva - 1mm from uppermost dermal papillae
- superficially invasive SCC of the cervix - FIGO - 5 mm depth or 7 mm width (from the basement membrane of the epithelium or CIN III in glands);
- SGO 3 mm, no vascular invasion


- Pathways of vulvar intraepithelial neoplasia and squamous cell carcinoma. Del Pino M, Rodriguez-Carunchio L, Ordi J. Histopathology. 2012 Sep 18. PMID: 23190170