Cidofovir has shown antiproliferative effects against human papillomavirus (HPV)-positive cells and successfully suppressed the growth of HPV-positive xenografts in athymic nude mice. The present study evaluated the effect of cidofovir on several disease parameters in this animal model. Intratumoral administration of cidofovir resulted in a beneficial effect on body weight gain, a reduction in splenomegaly, a partial restoration of tryptophan catabolism, and diminished the inflammatory state induced by the xenografts. Administration of cidofovir to tumor-free animals did not have a direct effect on these parameters. Beyond suppressing tumor growth, intratumoral treatment with cidofovir ameliorated the pathology associated with HPV-tumor growth.