Development of a Novel Mouse Model of Spontaneous High-Risk HPVE6/E7-Expressing Carcinoma in the Cervicovaginal Tract.

Current pre-clinical models for cervical cancer lack important clinical and pathological features. To improve upon these models, we aimed to develop a novel, spontaneous HPV16-expressing carcinoma model that captures major aspects of HPV-associated cancer in the female genital tract. This novel pre-clinical model features 1) expression of HPV oncogenes E6 and E7 in the tumors in female reproductive tract of mice, 2) spontaneous progression through high-grade squamous intraepithelial lesion (HSIL) to carcinoma, and 3) flexibility to model cancers from different high-risk HPV genotypes. This was accomplished by injecting plasmids expressing HPV16 E6/E7-Luciferase, AKT, c-myc, and Sleeping Beauty transposase into the cervicovaginal tract of C57BL/6 mice followed by electroporation. Cell lines derived from these tumors expressed HPV16 E6/E7 oncogenes, formed tumors in immunocompetent mice, and displayed carcinoma morphology. In all, this novel HPV-associated cervicogenital carcinoma model and HPV16E6/E7-expressing tumor cell line improves upon current HPV16-E6/E7-expressing tumor models. These tumor models may serve as important pre-clinical models for the development of therapeutic HPV vaccines or novel therapeutic interventions against HPV E6/E7-expressing tumors.