Validation of an HPV16-mediated Carcinogenesis Mouse Model

Background/Aim: Human papillomavirus Type 16 (HPV16) infection is a necessary but alone insufficient cause of invasive cervical cancer (ICC) and likely causes other genital cancers. Individual genetic variability influences the natural history of the neoplasm. Developing a variety of animal models to investigate HPV16-mediated carcinogenesis is important to Phase 1 trials for human cancer treatments. Materials and Methods: C57BL/6 mice expressing the HPV16- E7 transgene were treated with 100 nmoles of 7,12- dimethylbenz(a)anthracene (DMBA) on dorsal-thoracolumbar skin for ≤20 weeks. Results: Transgenic-HPV16E7 mice showed more tumors (14.11±1.49 vs. 7.2±0.73) that more quickly reached maximal size (17.53±0.53 vs. 28.75±0.67 weeks) than syngeneic controls. Conclusion: DMBA topically- treated C57BL/6-HPV16E7 mice developed chronic inflammation as well as benign and malignant lesions, many of which ulcerated. Histology showed that the HPV16-E7 transgene more than doubled the effect of complete carcinogenesis against a C57BL/6 background alone, strongly influencing the number, size, and time-to-maximal tumor burden for DMBA-exposed transgenic-C57BL/6 mice.