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Clinical and molecular classification of vulvar squamous pre-cancers
  1. Paul A Cohen1,2,
  2. Lyndal Anderson3,4,
  3. Lois Eva5,6 and
  4. James Scurry7,8
  1. 1Department of Gynaecological Oncology, St John of God Hospital Bendat Family Comprehensive Cancer Centre, Perth, Western Australia, Australia
  2. 2Division of Obstetrics and Gynaecology, Faculty of Health and Medical Sciences, University of Western Australia, Crawley, Western Australia, Australia
  3. 3Anatomical Pathology Department, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
  4. 4School of Medicine, Western Sydney University, Penrith South, New South Wales, Australia
  5. 5Department of Gynaecological Oncology, National Women's Health, Auckland City Hospital, Auckland, New Zealand
  6. 6Department of Gynaecological Oncology, University of Auckland, Auckland, New Zealand
  7. 7Pathology North, New Lambton Heights, New South Wales, Australia
  8. 8Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia
  1. Correspondence to Associate Professor Paul A Cohen, Gynaecological Oncology, St John of God Hospital Bendat Family Comprehensive Cancer Centre, Perth, WA 6008, Australia; paul.cohen{at}


Vulvar intraepithelial neoplasia (VIN) is a precursor to vulvar squamous cell carcinoma and is defined histopathologically by the presence of atypia. VIN has been classified into two types: usual vulvar intraepithelial neoplasia (uVIN), which is also referred to as a vulvar high-grade squamous intra-epithelial lesion (HSIL), and differentiated VIN (dVIN). The former is associated with chronic infection by sub-types of the human papilloma virus (HPV), whereas dVIN is HPV-independent and frequently associated with lichen sclerosus. The distinction is important because dVIN has a greater risk of, and more rapid transit to, vulvar squamous cell carcinoma. Furthermore, dVIN-associated vulvar cancers have an increased risk of recurrence and higher mortality than those arising from HSIL. Molecular characterization of vulvar squamous cell carcinoma precursors using next-generation sequencing is a relatively novel, but rapidly advancing field. This review appraises recent studies that have investigated the risks of progression to vulvar malignancy associated with HSIL and dVIN, the prognosis of HPV-dependent and HPV-independent vulvar squamous cell carcinomas, and conducted next generation sequencing mutation analyses to elucidate the genomic profiles underlying VIN. These studies suggest that HSIL and dVIN are characterized by different underlying molecular alterations that may have important implications for treatment and follow-up of women diagnosed with vulvar squamous cell cancer.

  • vulvar diseases
  • vulvar neoplasms

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  • Contributors PAC did the initial literature search. LA, LE, and JS reviewed the literature search and contributed with additional references from the literature. LE and JS provided the histopathology images. All authors wrote and approved the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.