Specifically, the cutaneous HPV E6 oncoproteins do not directly target p53 but have been shown to interfere with the tumor suppressive NOTCH and TGF-β signaling pathways by interacting with the key transcriptional co-activators, MAML1 and SMAD2/SMAD3, respectively (39, –, 42). Here, SMAD3 is linked to neoplasm.