Beta-Human Papillomaviruses (HPV) Are Common in Vulvar Squamous Cell Carcinomas and Surrounding Skin
A Glazyrin, A Rohwedder, JA Carlson. Albany Medical College, Albany, NY; Bio-Med Molecular Diagnosis, Kalkar, Germany
Background: Beta (epidermodysplasia verruciformis associated) HPV types are frequently associated with non-melanoma skin cancers. Their role in carcinogenesis has yet to be elucidated. Our objective was to determine the frequency of EV HPV types in vulvar cancers and surrounding skin.
Design: DNA was extracted from 315 paraffin blocks from 70 excisions from 67 women treated for vulvar neoplasia. These blocks consisted of 142 neoplastic, 137 inflammatory, 7 warts, and 29 normal skin specimens. These samples were tested for the presence of HPV DNA utilizing a broad spectrum of degenerate and type specific primers for alpha and beta HPV types. Expression of G1-S cell-cycle regulators p16, p21, p27, p53, cyclin D1 and retinoblastoma was performed by immunohistochemistry and correlated with HPV DNA status.
Results: HPV DNA was detected in 94% (63/67) of all patients and in 73% (23/315) of all samples- beta HPV genotypes in 82% of patients and 52% of all samples, alpha HPV in 80% and 48%, and co-infection with both in 69% and 27%, respectively. Alpha HPV genotypes detected were HPV 6 (7% of all types), 6c, 16 (32%), 18, 33, 52, 53, and 58, and beta HPV consisted of both known genotypes- HPV 5, 8, 12variant, 14d, 17, 20 (5%), 21, 22variant, 23variant, 36, 38 and 47, and twenty one putatively novel HPV genotypes (most common- DL285 19%). Vulvar squamous cell carcinomas (SCC) and adjacent skin samples could be divided into those associated with vulvar intraepithelial neoplasia (VIN)(41% of all samples) and those associated with lichen sclerosis (LS) (55%). As suspected, VIN and associated SCC and adjacent skin samples showed a strong and significant correlation between the presence of high-risk alpha HPV (16, 18, 33, 52 and 58) and a high p16LI (r=0.6, P=0.0001). In this group, HPV 16 was integrated into the host genome in 32%. In LS and associated SCC and adjacent skin samples, HPV 16 was detected in 30%, did not correlate with cell-cycle markers, and was episomal. In contrast, the presence of putatively oncogenic beta HPV (5, 8, 14d, 17, 20, 38, 47) and DL285 significantly correlated with elevated p21 expression in LS and its associated samples (r=0.3, P=0.0001). No correlation was detected between beta-HPV genotypes with G1-S cell markers for VIN and its surrounding skin samples.
Conclusions: Beta HPV genotypes are frequently present in vulvar SCC and its surrounding skin. HPV genotypes segregated into 2 histologic pathways to vulvar SCC: high risk alpha-HPV with VIN-SCC and oncogenic beta-HPV with LS-SCC.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 75, Monday Morning