Pathways of vulvar intraepithelial neoplasia and squamous cell carcinoma

Authors

  • Marta del Pino,

    1. Faculty of Medicine, Institute Clinic of Gynaecology, Obstetrics and Neonatology, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
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  • Leonardo Rodriguez-Carunchio,

    1. Department of Pathology, Faculty of Medicine, CRESIB (Centre de Recerca en Salut Internacional de Barcelona), Hospital Clinic, University of Barcelona, Barcelona, Spain
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  • Jaume Ordi

    Corresponding author
    1. Department of Pathology, Faculty of Medicine, CRESIB (Centre de Recerca en Salut Internacional de Barcelona), Hospital Clinic, University of Barcelona, Barcelona, Spain
    • Faculty of Medicine, Institute Clinic of Gynaecology, Obstetrics and Neonatology, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
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Address for correspondence: J Ordi, Department of Pathology, Faculty of Medicine, CRESIB, Hospital Clínic, University of Barcelona, C/Villarroel 170, 08036 Barcelona, Spain.

e-mail: jordi@clinic.ub.es

Abstract

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. p16INK4a 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.

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