Moreover, Metformin efficiently counteracted p53 and p21 induction by the Mdm2 inhibitor Nutlin‐3 [60] in both U2OS and HCT116 colon cancer cells (Figure S1D), further supporting the notion that Metformin can downregulate p53 via an HPV‐independent mechanism. This evidence concerns the gene MDM2 and malignant colon neoplasm.