We generated primary and orthotopic NPC models starting from normal nasopharyngeal epithelium with NPC related genetic drivers, a capable strategy that we have successfully applied for lung cancer,[21] gastric cancer,[22] bladder cancer,[23] and others.[24] With these models, we further investigated the biological functions of multiple important genetic alterations, including Trp53, Cdkn2a, and Tgfbr2 loss and LMP1 overexpression, during NPC initiation and development. Here, TP53 is linked to urinary bladder cancer.