Pitfalls in the Interpretation of p16 Immunohistochemistry and High-Risk HPV In Situ Hybridization in Head and Neck Cancer and Dysplasia.
Patricia Devilliers, Aleodor Andea. University of Alabama, Birmingham
Background: Immunohistochemical p16 expression (p16 IHC) may be used as a surrogate marker in the detection of high-risk human papillomavirus-associated head and neck cancer. High-risk HPV in situ hybridization (HR-HPV ISH) may be used as a confirmatory test on those cases positive for p16 IHC.
Design: A total of 130 cases of oropharyngeal cancer and dysplasia which had undergone HPV testing, as part of clinical care, during a 24 month period were selected, analyzed and correlated. HPV testing consisted of initial p16 IHC (MTM Laboratories, Westborough, MA), followed by high-risk HPV ISH (Ventana, USA).
Results: HPV status analysis was conducted on 100 oropharyngeal carcinomas and 30 cases of dysplasia. A total of 95% (95/100) of the tumors were positive for both p16 IHC and HR-HPV ISH, with the remaining 5% (5/100) positive for p16 and negative for HR-HPV ISH. Of the 30 cases of dysplasia, one third (10/30) consisted of mild dysplasia, which tested focally positive for p16 and negative for HR-HPV ISH. The remainder 2/3 (20/30) cases consisted of moderate to severe dysplasia, of which 27% (8/30) were focally positive for p16 and negative for HR-HPV ISH and 40% (12/30) had strong positivity for p16 and HR-HPV ISH. The staining pattern of p16 included cytoplasmic and nuclear. However, only those cases which were strongly positive for p16 nuclear and cytoplasmic staining were also positive for HR-HPV ISH. Regarding the staining pattern of ISH, areas of background staining of tissue not associated with the cells of interest were evident in all cases.
Conclusions: While incorporating p16 IHC and HR-HPV ISH to detect HPV in oropharyngeal carcinomas and severe dysplasias is a practical strategy, care ought to be taken when relying on the interpretation of p16 staining, considering positivity in cases showing more than 70% nuclear and cytoplasmic staining of the cells of interest. Dysplasias testing focally positive for p16, may be HR-HPV ISH negative. Moreover, cases of strong p16 IHC positivity which are negative for HR-HPV ISH may require further testing for wide spectrum HPV ISH.
Category: Head & Neck
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 139, Tuesday Afternoon