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Characterization of Squamous Cell Cancers of the Vulvar Anterior Fourchette by Human Papillomavirus, p16INK4a, and p53

Reuschenbach, Miriam MD1,2; Roos, Judith MD3; Panayotopoulos, Dimitrios MD4; Baldus, Stephan E. MD5; Schnürch, Hans-Georg MD3; Berger, Annemarie PhD6; Petry, Karl Ulrich MD7; Dürst, Matthias PhD8; Seiz, Mirjam1,2; von Knebel Doeberitz, Magnus MD1,2; Hampl, Monika MD4on behalf of the German Study Group for Colposcopy

Journal of Lower Genital Tract Disease: July 2013 - Volume 17 - Issue 3 - p 289–297
doi: 10.1097/LGT.0b013e31826f2b2b
Original Articles

Objective The incidence of vulvar squamous cell carcinomas located between the clitoris and urethra in young women is rising in distinct geographic regions, but characteristics of the tumors indicating certain carcinogenic mechanisms are unknown. The present study aimed at characterizing these vulvar cancers for their human papillomavirus (HPV), p16INK4a, and p53 status, revealing potential pathways of carcinogenesis.

Materials and Methods Squamous cell vulvar cancers of the anterior fourchette were retrospectively collected from 8 German hospitals, with additional squamous cell cancers located at other sites of the vulva from 2 of the hospitals. All tumors were analyzed for HPV DNA by polymerase chain reaction and for p16INK4a and p53 expression by immunohistochemistry.

Results Potentially HPV-associated tumors (HPV and p16INK4a positive, 21.4% [27/126] of the anterior fourchette and 27.7% [13/47] from other locations), p53-overexpressing tumors (35.7% [45/126] and 29.8% [14/47]), and a third group (HPV/p16 negative/p53 not overexpressed, 42.9% [54/126] and 42.6% [20/47]) were observed among tumors from the anterior fourchette as well as among vulvar cancers from other locations. Women with vulvar cancers of the anterior fourchette were of young age irrespective of the HPV/p16INK4a/p53 status.

Conclusions Different types of vulvar cancers can be found in squamous cell tumors of the anterior fourchette, similar to the finding in vulvar cancers from other locations and to what has previously been reported for vulvar squamous cell carcinomas in general.

Vulvar squamous cell cancers of the anterior fourchette are not different from vulvar cancers at other sites regarding the HPV, p16INK4a, and p53 status.

1Department of Applied Tumor Biology, Institute of Pathology, Ruprecht Karls University of Heidelberg; 2Clinical Cooperation Unit, German Cancer Research Center, Heidelberg; 3Department of Gynecology and Obstetrics, Lukaskrankenhaus, Neuss; 4Departments of Gynecology and Obstetrics, and 5Pathology, Heinrich Heine University of Düsseldorf, Düsseldorf; 6Institute of Medical Virology, Johann Wolfgang Goethe University of Frankfurt, Frankfurt; 7Department of Gynecology and Obstetrics, Klinikum Wolfsburg, Wolfsburg; and 8Department of Gynecology and Obstetrics, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany

Reprint requests to: Miriam Reuschenbach, MD, Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany. E-mail:

Magnus von Knebel Doeberitz was a member of the supervisory board and shareholder of mtm Laboratories at the time the study was conducted, and Karl Ulrich Petry received lecture honoraria from mtm Laboratories. The remaining authors declare no conflict of interest. Parts of the study were financially supported by Sanofi Pasteur MSD. mtm Laboratories AG provided the p16INK4a and Ki-67 antibodies for the study.

Copyright © 2013 by the American Society for Colposcopy and Cervical Pathology