Clinical Significance of p16 Positive but HPV Negative Oropharyngeal Squamous Cell Carcinoma
JS Lewis, Jr, WL Thorstad, J Zhang, JH Yip, SK El Mofty. Washington University, St. Louis, MO
Background: It is now generally accepted that human papilloma virus (HPV) related squamous cell carcinomas (SCC) of the oropharynx have more favorable clinical outcome than HPV unrelated tumors. It is therefore important to accurately identify tumors that are HPV driven. For this purpose, most pathologists use a combination of both p16 immunohistochemistry (IHC) and HPV in situ hybridization (ISH). A significant minority of tumors are p16 positive but ISH HPV negative, the significance of which is unclear. The purpose of this study was to compare the clinical outcome in patients with p16 positive, HPV negative tumors to those with tumors that are positive for both p16 and HPV.
Design: 234 oropharyngeal SCC with clinical follow-up were identified from clinician databases at Washington University from 1997 to 2008. These were tested by IHC for p16 and by ISH for high-risk HPV. For p16 positive, HPV ISH negative cases, PCR was performed for high risk HPV that might not have been detected by ISH. Statistical analysis was done by log-rank tests for the equality of survivor functions and Cox Proportional Hazards regression analysis.
Results: Of the 234 cases, 187 (80%) were positive for p16. Of these, 139 (74%) were positive for HPV by ISH. Of the remaining 48 cases, 45 had material for PCR. 13 were positive for high risk HPV, leaving 32 p16 positive but HPV ISH and PCR negative SCCs. Among the p16 positive tumors, no significant differences in overall, disease specific, or disease free survival (p=0.38, 0.33, and 0.39) were observed between those that were HPV ISH positive and those that were ISH negative. Similarly, no differences were observed in overall, disease specific, or disease free survival (p=0.13, 0.12, and 0.13) between those that were HPV ISH positive and those that were ISH and PCR negative. However, p16 positive, HPV negative SCC had significantly better overall, disease specific, and disease free survival (p=0.0002, 0.0058, and 0.0125) than p16 and HPV negative SCC.
Conclusions: p16 positive, HPV negative oropharyngeal SCC has survival rates that are not significantly different from p16 positive, HPV positive tumors, but which are significantly better than p16 negative, HPV negative tumors. This data argues that HPV-specific testing adds little useful information in addition to p16 immunohistochemistry.
Category: Head & Neck
Tuesday, March 23, 2010 8:30 AM
Platform Session: Section G, Tuesday Morning