Vulvar squamous cell carcinoma development after diagnosis of VIN increases with age Hedwig P. van de Nieuwenhof a, * , Leon F.A.G. Massuger a , Irene A.M. van der Avoort a , Ruud L.M. Bekkers a , Mariel Casparie b , Wim Abma a , Le ´on C.L.T. van Kempen c , Joanne A. de Hullu a a Department of Obstetrics and Gynaecology (791), Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands b Foundation PALGA, Nationwide Netherlands Database of Histo- and Cytopathology, The Netherlands c Department of Pathology, Radboud University Nijmegen Medical Centre, The Netherlands ARTICLE INFO Article history: Received 2 September 2008 Received in revised form 20 November 2008 Accepted 25 November 2008 Available online 29 December 2008 Keywords: Usual VIN Differentiated VIN Vulvar squamous cell carcinoma Incidence Malignant potential ABSTRACT Objective: The purpose of the present study is to investigate the trends in incidence of both usual (u) and differentiated (d) vulvar intraepithelial neoplasia (VIN) separately, their malig- nant potential and the relation with other HPV related anogenital lesions in the Nether- lands during a 14-year-period. Methods: The incidences of both types of VIN and vulvar SCC were retrieved from the Nationwide Netherlands Database of Histo- and Cytopathology. Population data were retrieved from the Database of Statistics Netherlands. Results: In the study period, the incidence of uVIN and dVIN increased, while the incidence of vulvar SCC remained stable. The overall percentage of uVIN patients that were later diag- nosed with vulvar SCC was 5.7%, which was significantly lower than the percentage for dVIN patients (32.8%). In addition to this 5.6-fold increased conversion rate, the time of pro- gression from dVIN to SCC development was significantly shorter than that of uVIN (p = 0.005). Percentage of uVIN patients that were later diagnosed with SCC significantly increased with age (p = 0.005), whereas the time to SCC significantly shortened with age (p = 0.05). Forty-one percent of uVIN patients had a past, concomitant or future HPV-asso- ciated lesion of the lower genital tract, which is in contrast to the 3% for dVIN patients. Conclusions: An increase in diagnoses of both uVIN and dVIN has not led to an increase in vulvar SCC incidence. The malignant potential of dVIN is higher than that for uVIN. For uVIN the malignant potential increases with age. Ó 2008 Elsevier Ltd. All rights reserved. 1. Introduction Vulvar squamous cell carcinoma (SCC) is the fourth most com- mon gynaecological type of cancer with an annual incidence of 2–3 per 100,000 women. 1,2 Vulvar SCC usually arises from pre- malignant vulvar intraepithelial neoplasia (VIN). In general, there are two different types of VIN, i.e. differentiated VIN (dVIN) and usual VIN (uVIN) that both can progress towards vulvar SCC. 3–5 Whereas uVIN is causally related with human papillomavirus (HPV) infection, dVIN is HPV unrelated. 5 dVIN is a recently recognised but difficult to diagnose entity for clinicians as well as pathologists. 4,6 dVIN is found 0959-8049/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejca.2008.11.037 * Corresponding author: Tel.: +31 24 3666455; fax: +31 24 3668597. E-mail address: H.Nieuwenhof@obgyn.umcn.nl (H.P. van de Nieuwenhof). EUROPEAN JOURNAL OF CANCER 45 (2009) 851 – 856 available at www.sciencedirect.com journal homepage: www.ejconline.com