This edition of Head and Neck has a strong focus on studies using immunohistochemistry (IHC) to elucidate potential roles of various cell-signalling molecules in both HNSCC and thyroid cancer. The ‘cellular-protein heavy’ title of this article may be off-putting to the casual reader, but it belies what is quite an accessible, relevant article, and explains concisely what they are investigating with the aid of schematic diagrams. Overall, this study starts the process of identifying if KPNA2, a transport protein found in saliva, could be used in the future to aid both early diagnosis, and prognosis, in oral cavity SCC. This team from Taiwan used IHC and ELISA to examine a total of 209 tissue specimens and 181 saliva samples (35 healthy controls, 35 early stage oral SCC and 81 late stage). They looked at three elements of KPNA2: molecular mechanism, functional characterisation and clinical significance. This protein is already known to be involved in numerous cancers, with a strong association with tumour invasiveness and poor prognosis, but this is the first paper looking at its role in oral cavity SCC. In terms of explaining how KPNA2 plays a role in oral cavity SCC specifically, this paper has identified that KPNA2 is required for matrix-metalloproteinase-mediated metastasis and reduces IL1ß-induced import of NFκB. The results also revealed that KPNA2 is highly overexpressed in oral cavity SCC and there is positive correlation with extra-nodal extension, which they suggest may indicate a link to phenotypic expression which results in a more invasive cancer. In their multivariate analysis they found that KPNA2 overexpression was an independent prognostic factor of disease specific survival in patients with stage III to IV disease. When considering whether this biomarker has a role in a future screening tool, their results (although limited by relatively small sample numbers) show that KPNA2 levels are higher in patients with oral cavity SCC compared with healthy controls, particularly patients with late stage disease.