CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Overall, the data showed that while p16 positivity in the head and neck correlated with HPV status, p16 positivity outside of the head and neck did not. This brings up a diagnostic pitfall with regard to p16 staining in cytology specimens. The data suggest that p16 staining outside of the head and neck should not be used as a surrogate for HPV-related cancers, and the data also draw attention to the incidence of non-HPV–related p16-positive cancers metastasizing to the head and neck. Diffuse p16 staining can be seen in a variety of conditions such as adenocarcinoma, small cell carcinoma, and serous carcinoma irrespective of body site. Focal p16 can also be seen in adenocarcinomas. Therefore, HPV cotesting should be pursued in p16-positive cases outside of the head and neck where an HPV-related primary is suspected, and clinical follow-up is warranted to determine the primary site.
Future studies will be needed to establish a consensus for the interpretation of p16 immunostaining both within and outside of the head and neck. It is possible that differences in percentage of p16 staining may correlate with HPV status in other body sites. As HPV testing is not routinely ordered in non-head and neck specimens that were stained with p16, it will be important to continue to gather more data to come to a consensus on this topic. Therefore, caution is warranted when ordering p16 stains outside of the head and neck as this stain is not specific for a single diagnosis in and of itself. Cytomorphologic correlation with intensity of p16, clinical history, and other ancillary studies such as p40 immunostaining and HPV cotesting can improve diagnostic accuracy and prevent diagnostic pitfalls.n
Dr. Ribeiro, a junior member of the CAP Cytopathology Committee, is the 2021–2022 Dr. Dorothy Rosenthal cytopathology fellow, Department of Pathology, Johns Hopkins Hospital.