Compound 12 is an inhibitor of E6-mediated degradation of p53 through the disruption of E6-p53 binding in vitro and in human papillomavirus (HPV) cells.  HPV-E6 oncoprotein promoted p53 degradation is linked to tumor progression.  Compound 12 could restore p53 intracellular levels and transcriptional activity, reduce viability and proliferation of HPV-positive cancer cell and block 3D cervosphere formation.  Compound 12 exerts antitumor activity by inducing cell cycle arrest and senescence.  Compound 12 presents a new approach for anti-HPV drug development.