Our study reveals that Piwil2 activates multiple germline factors, such as c-Myc, Sox2, Nanog, Oct4, and Klf4, through epigenetic programming and subsequently reprograms somatic cells into tumor-initiating cells (TICs), thus offering a potential therapeutic target for patients with cervical cancer and especially CIN lesions. Here, POU5F1 is linked to cervical cancer.