Our results indicate that in HNSCC, performing p16 and p53 IHC staining simultaneously can aid in the interpretation of both stains and potentially reduce the need for additional HPV or mutational testing to only selected cases, allowing for accurate subclassification into HPV-associated and HPV-independent tumours, with the potential for further subclassification of the latter into p53abn and p53 wt (Fig. 6). Here, CDKN2A is linked to neoplasm.