1. ¹DDL Diagnostic Laboratory, Voorburg, The Netherlands
2. ²Department of Pathology, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, NY, USA

Correspondence: Dr EC Pirog, MD, Department of Pathology, Weill Medical College of Cornell University, New York-Presbyterian Hospital, 525 E 68th Street, F-766, New York, NY 10065-4897, USA. E-mail: ecpirog@med.cornell.edu

Received 10 October 2007; Revised 19 November 2007; Accepted 26 November 2007; Published online 11 January 2008.

Abstract

Two independent pathways of vulvar carcinogenesis have currently been identified, one related to infection with mucosal human papillomaviruses (HPVs) and a second related to chronic inflammatory or autoimmune processes. The goal of the study was to examine a possible role of cutaneous HPVs from the beta genus in vulvar carcinogenesis and to evaluate the distribution of intratypic variants of HPV 16 in HPV 16-positive vulvar cancer. Consecutive cases of vulvar carcinoma were retrieved from the files and included the following histologic subtypes: keratinizing (n=21), basaloid (n=7), warty (n=1), mixed basaloid–warty (n=4), verrucous (n=4), keratoacanthoma (n=1), basal cell carcinoma (n=1). All tumors were microdissected and tested for 25 beta HPV types and 25 mucosal HPV types. Cases identified as positive for HPV 16 were further tested for intratypic variants. All cases were immunostained for p16^INK4a. Beta HPVs were not detected in any of the tumor cases. Mucosal HPVs were detected in all but one basaloid/warty carcinomas; of these, nine cases (82%) were positive for HPV 16, including five European subtypes, one African subtype, one North American subtype and two indeterminate subtypes. Two of four verrucous carcinomas were positive for HPV 6. Mucosal HPVs were not detected in keratinizing carcinomas, keratoacanthoma and basal cell carcinoma. All cases of basaloid/warty carcinomas, but none of the remaining tumors, overexpressed p16^INK4a protein. Our data do not support a role of beta HPVs in the pathogenesis of vulvar carcinoma. The study reaffirms the role of mucosal HPVs, in particular that of HPV 16, in the pathogenesis of basaloid and warty tumor subtypes. The HPV 16 intratypic variation showed correlation with patients' ethnic background. P16^INK4a immunostaining seems to be a sensitive and specific marker of vulvar carcinomas positive for oncogenic mucosal HPVs.