Pathways of vulvar intraepithelial neoplasia and squamous cell carcinoma

Histopathology. 2013 Jan;62(1):161-75. doi: 10.1111/his.12034. Epub 2012 Nov 27.


Vulvar squamous cell carcinoma (VSCC) accounts for >90% of the malignant tumours of the vulva. Most VSCCs originate in intraepithelial lesions, named 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. Although large, multicentre studies are needed to definitively assess the involvement of HPV in the prognosis of VSCC, most studies have not found clear differences in survival between HPV-associated and HPV-independent tumours.

Publication types

  • Review

MeSH terms

  • Alphapapillomavirus / isolation & purification
  • Carcinoma in Situ / genetics
  • Carcinoma in Situ / pathology*
  • Carcinoma in Situ / virology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / virology
  • Condylomata Acuminata / pathology
  • Condylomata Acuminata / virology
  • Female
  • Gene Silencing
  • Genes, p53 / genetics
  • Humans
  • Lichen Sclerosus et Atrophicus / pathology
  • Lichen Sclerosus et Atrophicus / virology
  • Mutation
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / pathology
  • Precancerous Conditions / genetics
  • Precancerous Conditions / pathology*
  • Precancerous Conditions / virology
  • Prognosis
  • Vulvar Neoplasms / genetics
  • Vulvar Neoplasms / pathology*
  • Vulvar Neoplasms / virology