Distinguishing between distant metastases of HPV-related oropharyngeal squamous cell carcinoma (OPSCC) and metachronous primary lung squamous cell carcinoma (SCC) is important as it has implications for treatment, prognosis counselling, and registry data. Although p16 immunohistochemistry (p16 IHC) is widely accepted as a surrogate marker for HPV-related OPSCC, this is not the case for lung SCC. Furthermore, the morphological features of OPSCC can overlap with primary lung SCC and are insufficient to distinguish between the two. The authors therefore present a simple algorithm for the histological evaluation of suspected lung SCC nodules in patients with a history of OPSCC.
The algorithm involves p16 IHC for all suspected lung SCC nodules. If it is p16 negative, the nodule is likely to be a primary lung SCC and no HPV in situ hybridization (HPV ISH) is performed. If it is p16 positive, HPV ISH is also performed. If it is HPV ISH positive, it is considered an OPSCC distant metastasis, and if it is HPV ISH negative, it is considered a primary lung SCC.
In addition, this article reminds us of the limitations of the different histological diagnostic tests for HPV (such as p16 IHC and HPV ISH) in OPSCC cases, its differences in sensitivity / specificity between tumour sites, and when they are used in combination.