PTPN14 and cervical cancer: Through structure-based mutagenesis abrogating the HPV18 E7–PTPN14 binding, we demonstrate that the intermolecular interaction is significantly associated with HPV18-mediated proteasomal degradation of PTPN14, up-regulation of Hippo signaling downstream effectors, and enhanced cell proliferation, migration, and invasion, which was verified at a cellular level using nontumorigenic keratinocytes and HPV-positive or negative cervical cancer cells.