Furthermore, it cannot be excluded that the oncogenic phenotypes of proliferation, colony formation, cell cycling and invasion of HPV-negative HNSCC cells may not only be mediated by the transcriptional functions of SMYD3 in the nucleus of HPV-negative HNSCC cells, but they may also be induced by cytoplasmic functions of SMYD3 through direct methylation of non-histone substrates, as previously reported for other cancer types8–10. The gene discussed is SMYD3; the disease is cancer.