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Is Differentiated Vulval Intraepithelial Neoplasia the Precursor Lesion of Human Papillomavirus-Negative Vulval Squamous Cell Carcinoma?
  1. Fani Kokka, MD, MRCOG*,
  2. Naveena Singh, MD,
  3. Asma Faruqi, MD,
  4. Karen Gibbon, MD and
  5. Adam N. Rosenthal, MD, MRCOG, PhD*,§
  1. *Departments of Gynaecological Oncology,
  2. Departments of Histopathology, and
  3. Departments of Centre of Cutaneous Research, Barts and The London NHS Trust; and
  4. §Departments of Barts Cancer Institute-A CR UK Centre of Excellence, London, UK.
  1. Address correspondence and reprint requests to Fani Kokka, MD, MRCOG, 7th Gloucester House, St Bartholomew's Hospital, West Smithfield, London, UK EC1A 7BE. E-mail: Fani.Kokka{at}


Vulval squamous cell carcinoma appears to arise via 2 distinct pathways. A significant minority are associated with oncogenic human papillomavirus (HPV) infection and undifferentiated vulval intraepithelial neoplasia (VIN). However, the majority arises in the absence of HPV, on a background of chronic inflammation. Until recently, it was assumed that lichen sclerosus was the underlying inflammatory condition in the majority of HPV-negative cancers. This pathway of carcinogenesis has been less well studied than the HPV pathway. Emerging evidence implicates differentiated VIN (DVIN), rather than lichen sclerosus, as the most likely precursor lesion in HPV-negative vulval squamous cell carcinoma. Here we discuss the clinical and molecular evidence that implicates DVIN as a lesion with a high malignant potential. This lesion is probably underdiagnosed and may be undertreated. Better recognition of DVIN by gynecologists and pathologists may therefore offer an opportunity to prevent some vulval cancers.

  • Differentiated
  • Vulval intraepithelial neoplasia
  • Cancer
  • Vulva
  • Squamous
  • Etiology
  • Carcinogenesis
  • Hyperplasia

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  • This study was supported by the Griffiths Gynaecology Special Purpose Fund.