Cancer of the genital tract is the final outcome of some infections with human papillomavirus (HPVs), and the most estrogen-sensitive cells are at greatest risk for the HPV-related cancers. Therefore we investigated relationships between HPVs and estrogen metabolism in cells of the genital tract. Increased conversion of estradiol to 16 alpha-hydroxyestrone, known to be a risk factor for cancer in some other estrogen-sensitive cells, was investigated in keratinocytes from the genital tract. Primary cells, particularly those explants from the transformation zone of the cervix, are able to 16 alpha-hydroxylate estradiol. Both cervical and foreskin cells immortalized with HPV-16 are greatly enhanced in the 16 alpha-hydroxylation of estradiol as compared with normal cells. We suggest a model whereby the combined action of 16 alpha-hydroxylation of estrogen and HPV work together to promote cell proliferation.