Cervical infections by approximately 15 human papillomavirus (HPV) types are the necessary cause of cervical cancer and its immediate precursor lesions. However, oncogenic HPV infections are usually benign and usually resolve within 1-2 years. A few of these infections persist and progress to cervical precancer and cancer. A number of cervical factors, such as infection by sexually transmitted pathogens other than HPV, cervical inflammation, and antioxidant nutrients, may influence the natural history of HPV infection along the pathways of persistence and progression or resolution. We examine the possible roles of these HPV cofactors in cervical carcinogenesis and discuss new methodologies that may enable researchers to measure relevant markers of the cervical microenvironment in which these cofactors may be active.