Equivocal p16 Immunostaining in Head & Neck Carcinoma: Staining Pattern May Determine HPV Status.
Z Will W Chen, Ilan J Weinreb, Suzanne Kamel-Reid, Bayardo Perez-Ordonez. University Health Network, University of Toronto, ON, Canada
Background: P16 immunohistochemistry (IHC) is commonly used as a surrogate marker for human papilloma virus (HPV) detection in squamous cell carcinomas of the head and neck (SCCHN), especially in the tonsil and tongue base. However, the HPV status of tumors not staining strongly/diffusely for p16 is difficult to interpret. These cases may require the use of PCR, a costlier procedure than IHC, as a final arbiter of HPV status. We aim to determine if certain staining patterns or tumor characteristics in cases of equivocal p16 staining are predictive of PCR HPV status.
Design: A retrospective review was performed on pathology reports of all SCCHN that underwent p16 IHC and PCR with a linear array HPV genotyping test kit (Roche Diagnostics, Laval, Canada) in our institution. Each report with equivocal p16 IHC results (i.e. focal, weak, inconclusive or equivocal staining) was compared to the final PCR report. Keywords describing the staining pattern in the p16 IHC report in addition to tumor characteristics such as age, sex, site and diagnosis were compared to the final PCR HPV status. Statistical analysis was performed using the χ2 test.
Results: Thirty-one of 92 (34%) SCCHN that underwent PCR HPV testing from 2007-2010 had equivocal p16 IHC results. Of these, 13 (42%) tested positive and 18 (58%) negative for HPV by PCR. Mean age was 61.5 (range 43-70) with a male/female ratio of 2.1. Specimen sites included tongue, oral cavity mucosa, larynx, tonsil and neck lymph node. Diagnoses included conventional SCC, non-keratinizing SCC and SCC in-situ. Comparing age, sex, tumor site and diagnosis to HPV PCR status showed no statistically significant findings. However, comparing IHC staining keywords to HPV status was statistically significant (χ2=22.1; p=0.0002) with isolated staining strongly associated with negative HPV status and equivocal associated with positive HPV status.
|Staining pattern keyword||No. of cases with HPV+ PCR||No. of cases with HPV- PCR|
|Focal & weak||3||0|