Human papillomavirus (HPV) is a sexually transmitted virus that is associated with increased risk of anogenital cancers in immunosuppressed hosts. The behavior of HPV infection is controlled by the systemic immune system response as well as the local tissue immune system to the HPV virus. Individuals with a depressed immune system, either by viral infection (such as human immunodeficiency virus) or by chronic immunosuppressive agents (such as transplant recipients or patients with autoimmune disease) are at an increased risk of HPV-associated malignancies. This article addresses the data and limitations in developing evidence-driven guidelines for cervical cancer screening in immunocompromised women.