Chapter 44: The Acquired Immunodeficiency Syndrome–Related Cancers

THE CHANGING INCIDENCE OF MALIGNANCIES IN PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS DISEASE

The relationship between malignancies and acquired immunodeficiency syndrome (AIDS) changed in 1996 when highly active antiretroviral therapy (HAART) was introduced in industrial nations. Thanks to the United Nations and other philanthropy programs, HAART has also been successfully introduced into a number of developing nations (¹). Africa, the pandemic epicenter, is the exception, due to the epidemic magnitude on that continent and its significant political and social turmoil. Prior to 1996, epidemiologists noted specific malignancies afflicting patients with AIDS, with a risk proportional to host immune status. Before HAART, AIDS patients could be separated into two groups: patients with an opportunistic infection as their first manifestation of AIDS (60%) and those with a malignancy as its mode of presentation (40%) (²).

Of those with an AIDS-related malignancy, up to 90% would have Kaposi sarcoma (KS) and the rest non-Hodgkin lymphomas (NHLs), including primary central nervous system lymphoma (PCNSL) and systemic diffuse large B-cell lymphoma (DLBCL). Despite an increase in human papilloma virus (HPV)-related invasive cervical cancers in women with high-grade uterine cervical dysplasia, recent findings of a lack of clear association between cervical cancer and human immunodeficiency virus (HIV)-related immunosuppression questions the validity of including cervical cancer among AIDS-defining or associated malignancies (³). After HAART, previously obvious relationships between AIDS and some malignancies have been challenged. An example is HIV-related Burkitt lymphoma, initially associated with AIDS-induced immunosuppression. Investigators have found that HAART improvement of immunity is associated with significant reductions in KS, PCNSL, and systemic DLBCL, but this is not the case with Burkitt lymphoma. Together with invasive cervical cancer, the incidence of Burkitt lymphoma has remained stable across the pre- and post-HAART eras, increasing its proportional frequency. Epithelial dysplasia and squamous cell carcinomas of the anal canal, rectum, and oral cavity are also observed in men infected by HIV. There has been a post-HAART era increase in Hodgkin lymphoma (Epstein-Barr virus related), lung cancer, and nonmelanoma skin cancer, with implications related to the complex relationship between immunity, aging, chronic antigenic stimulation, and viral oncogenesis. Overall, the excess risk of a malignancy in HIV disease is observed mostly in cancers with an established or suspected infectious cause (⁴).

In this chapter, we first discuss HIV and its effect on the immune system. We then concentrate on malignancies associated with AIDS immunosuppression. We include a discussion of malignancies (Burkitt lymphoma and HPV-related cancers) not directly associated with HIV immunosuppression occurring with a high enough incidence in HIV-infected patients to merit study.

HUMAN IMMUNODEFICIENCY VIRUS DISEASE

Historical Significance of the Virus

The AIDS pandemic came into the medical world in 1980 with the publication in the Center for Diseases Control and Prevention (CDC) journal Morbidity and Mortality Weekly Report of a series of patients afflicted by ...