HPV-31 Is the Most Common HPV Subtype Isolated from Oropharyngeal Squamous Cell Carcinomas in South Africa
Cherie Paquette, Mark F Evans, Shabnum Meer, Vanitha Rajendran, Christine S Adamson, Kumarasen Cooper. Fletcher Allen Health Care, Burlington, VT; University of Vermont, Burlington, VT; University of the Witwatersrand, Johannesburg, South Africa
Background: Oropharyngeal squamous cell carcinomas (OSCCs) are associated with two main risk pathways: chemical (tobacco and alcohol) and human papillomavirus (HPV) infection. For the latter, HPV-16 has been implicated as the key etiologic subtype worldwide. However, data are scarce regarding OSCC in South African (SA) patients; three prior studies suggested no significant role for the virus, in contrast to worldwide trends. We aimed to assess SA OSCCs for HPV, determine virus genotype, and investigate p16INK4a immunohistochemical (IHC) positivity as a marker for HPV-driven tumors.
Design: Formalin-fixed, paraffin-embedded tissues from 67 OSCCs collected between 2005 and 2010 from South African patients were analyzed for HPV DNA via PCR (positive results genotyped by sequencing), chromogenic in situ hybridization (CISH), and p16INK4a IHC. Two cases were excluded (non-diagnostic tissue and respiratory papillomatosis).
Results: We analyzed 65 OSCCs from 54 patients (mean age 58, 80% male, 76% black and 24% Caucasian). Of the samples 48 (74%) were HPV positive by PCR: 34 (71%) HPV-31, 6 (12%) HPV-16, 4 (8%) HPV-18, 2 (4%) 'untypeable' and one each (4%) combined HPV-16/31 or HPV-18/31. CISH was negative in all cases. Of the 34 p16INK4a IHC positive cases, 26 (76%) were positive for HPV by PCR. Of the 31 p16INK4a IHC negative cases, 22 (71%) cases were positive for HPV by PCR.
Conclusions: In accordance with worldwide epidemiologic data, HPV appears to play a role in the pathogenesis of OSCC in South Africa, with strongest evidence for OSCCs positive for both p16INK4a IHC and HPV by PCR, comprising 40% of our tumor samples. The p16INK4a IHC stain is used as a marker for HPV-related tumors, and may help distinguish HPV-driven tumors from tumors with incidental HPV. Contrary to the results of meta-analyses derived primarily from Western patient cohorts, HPV-31, and not HPV-16, was the predominant genotype identified. The absence of specific assays for HPV-31 in previous SA studies may explain our present findings. Further studies, including HPV-31 viral load and alternative CISH methodologies, must be investigated to corroborate our data.
Category: Head & Neck
Monday, March 19, 2012 1:45 PM
Platform Session: Section F, Monday Afternoon