Verrucous Carcinoma May Arise Via HPV-Dependent or HPV-Independent Routes That Are Not Predictable from p16INK4a Immunostaining
ED Dulaney, MF Evans, CS Adamson, Z Peng, V Rajendran, K Cooper. University of Vermont/Fletcher Allen Health Care, Burlington, VT
Background: Verrucous carcinoma (VC) is a rare subtype of squamous cell carcinoma with unique clinicopathologic features, occurring in oral, genital, perianal and occasionally cutaneous locations. Previous studies have yielded conflicting data on the prevalence of human papilloma virus (HPV) and the specific genotypes found in VC. In addition, these studies have been restricted to VC in one or two anatomic sites.
Design: Search of our pathology department's computerized database for VC diagnosed between May, 1978 and February, 2009 identified 10 cases available for analysis: 1 anal, 3 vulvar and 6 oral specimens. The polymerase chain reaction (PCR), chromogenic in situ hybridization (CISH), and immunohistochemistry (IHC) for p16INK4a were combined to investigate HPV infections in these tumors.
Results: HPV DNA was detected in seven VCs (70%) by PCR, identifying HPV31 in 3 cases (2 oral, 1 vulvar), HPV16 in two cases (1 vulvar, 1 oral), and single cases of HPV6 (oral) and HPV11 (anal). HPV was detectable by CISH in 5 PCR-positive cases: 2 vulvar (1 HPV16, 1 HPV31 [punctate nuclear signals, integrated HPV]), 1 anal (HPV11, diffuse nuclear signals [episomal HPV]) and 2 oral (1 HPV16, 1 HPV31 [punctate nuclear signals, integrated HPV]). Three PCR/CISH-positive samples demonstrated p16 INK4a staining. Overall, p16 INK4a IHC correlated with PCR results in 5 cases (50%) and with CISH results in 5 cases (50%).
Conclusions: These data indicate that VC from diverse anatomic locations may arise via HPV-dependent or HPV-independent routes. The HPV route may involve high risk (16, 31) or low risk (6, 11) HPV subtypes. However, it is also possible that HPV may be incidental to VC etiology in the cases positive for HPV by PCR only. Staining for p16INK4a does not appear to be a simple surrogate marker for HPV in VC.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 221, Wednesday Morning