HPSE and cervical carcinoma: In summary, our results provide the first evidence for a functional involvement of HPV E6 in heparanase induction during head and neck tumourigenesis (most likely through p53-dependent mechanism) and may provide important avenue for future therapeutic exploration, relevant not only for HNSCC, but also for additional HPV-associated tumours, including cervical carcinoma (where heparanase overexpression is associated with aggressiveness and poor prognosis 44) and other types of lower genital tract neoplasms caused by HPV infection.