p16 immunohistochemistry for primary tumor detection in HPV-positive squamous cell carcinoma of unknown primary

To examine the potential benefit of reevaluation of original slides and p16 immunohistochemistry (IHC) of tonsillectomy specimens for primary tumor identification in cases of human papillomavirus (HPV) positive squamous cell carcinoma (SCC) of the head and neck of unknown primary.

Through a retrospective review, we identified all patients 18 or older who presented at our institution from 2003 to 2015 with histologically confirmed HPV-positive SCC in a cervical lymph node with unidentified primary tumor after initial workup. For patients for whom specimens were available, an expert head and neck pathologist re-reviewed original hematoxylin and eosin (H&E) slides to confirm absence of tumor and performed p16 IHC and deep sectioning of tissue blocks to identify potential tumor foci.

Among 735 patient records assessed, 80 were HPV-positive SCC with unknown primary, 28 of which did not have a primary tumor identified, and 20 with original specimens available. Upon re-review of 103 original H&E slides, invasive SCC was identified for 2 patients. Deep sectioning and p16 IHC did not identify additional primary tumors.

Re-review of original slides by an expert head and neck pathologist, but not p16 staining or deeper H&E sections, was able to identify additional tumors.