Research has confirmed that high expression of MMPs, especially MMP-2, and tissue inhibitors of metalloproteinase-2 (TIMP-2) is closely associated with high aggressiveness and poor prognosis.178 HPV-16 E7 upregulates the activity of MMP-9 and downregulates proteins, including cysteine-rich proteins with kazal motif gene and TIMP-2, which inhibits the activity of MMP-9, thus contributing to cell invasion and tumor metastasis.179 HPV-18 E7 synergistically enhances the expression of MMPs in conjunction with H-rasV12, mediated by the MEK/ERK pathway. This evidence concerns the gene TIMP2 and neoplasm.