Moreover, in vitro and in vivo HNSCC xenograft models combined with patient data have revealed two different ways by which p16, the surrogate marker for HPV infection, contributes to different dissemination patterns: (1) regulating vascular invasiveness and angiogenesis and (2) stimulating nodal spread by increasing lymphatic vessel formation via alpha4 beta1 integrin upregulation [59]. The gene discussed is CDKN2A; the disease is head and neck squamous cell carcinoma.