Infection with Human papillomavirus (HPV) is prolific around the world and is of great concern due to its high rate of transmission and ability to cause anogenital and head and neck cancers. Although vaccine use is becoming increasingly widespread, there are still unvaccinated individuals, those who have already contracted the virus, and cancer-associated strains that are not targeted by all HPV vaccines. Additionally, there is no available treatment for most infections. Therefore, there is a critical need for effective antivirals against HPV. It is well known that the HPV E6 and E7 proteins are responsible for the growth of HPV-associated cancers and that these are required for cancer cell survival and proliferation. Our group previously demonstrated the role of the MEK/ERK signaling pathway in promoting expression of E6 and E7 and the efficacy of a MEK1/2 inhibitor in a preclinical mouse papillomavirus model. This is the first demonstration of an effective antiviral in the MmuPV1 model and our results warrant further investigation. We are currently determining the potential for increased efficacy of MEK inhibitors by the addition of JNK inhibition, which targets a parallel signaling cascade upstream of E6/E7 production, as well as topical delivery of antiviral treatment.