Malignancies have been detected in approximately 40% of all patients with acquired immunodeficiency syndrome (AIDS) sometime during the course of their illness. These cancers have been both a primary cause of death in some patients and also a source of considerable morbidity. In the current era of highly active antiretroviral therapy (HAART), patients infected with the human immunodeficiency virus (HIV) are surviving longer than ever. HAART appears to have substantially reduced the incidence of Kaposi’s sarcoma (KS) and non-Hodgkin lymphoma (NHL) and may enhance the efficacy of treatment for those patients who do develop these tumors. Unfortunately, HAART has not shown a similar effect on the development of other types of neoplasms, and caring for patients who develop malignancies in the setting of HIV remains a challenge. Furthermore, HAART is not available universally, with many patients in resource-poor developing countries not having access to antiretroviral drugs.
KS has been the most common tumor associated with HIV infection, but it currently develops in < 10% of homosexual men with AIDS in the United States and in 1% to 2% of other HIV-infected persons. The incidence of KS has declined substantially, from 4.8 per 100 person-years in 1990 to 1.5 per 100 person-years in 1997. In 2003, a European study found that the incidence of KS among HIV-infected individuals was less than 10% of the incidence seen a decade earlier in 1994.
Among AIDS patients in the United States, the incidence of KS is higher in males than in females. There is also a higher incidence of KS in men than in women in Africa (male-female ratio, 2:1), despite the equal prevalence of HIV infection among men and women.
The age distribution of AIDS-related KS follows the distribution of HIV infection. As such, AIDS-related KS can occur in all age groups. In American adult males, the most common age of onset of AIDS-related KS is 30 to 40 years old. No peak age has been reported.
No racial or ethnic differences in the incidence of AIDS-related KS have been observed.
In the United States, KS is seen in < 10% of homosexual men with AIDS. The proportion of KS among AIDS-defining diagnoses is lower in parts of Europe, where there are proportionately fewer male homosexual AIDS cases (eg, 6.8% of Italian AIDS patients), and higher in parts of Africa, where KS is endemic in the non–HIV-infected population. Among AIDS cases in the United States, the proportion of patients with KS has declined from the beginning of the AIDS epidemic, possibly as a result of changes in high-risk sexual behavior among homosexual men and the wider use of more effective antiretroviral combination regimens.
Etiology and risk factors
In 1994, unique viral DNA sequences were identified in tumor tissues from patients with AIDS-related KS, which led to the identification of a new virus called KS-associated herpesvirus (KSHV) or human herpesvirus type 8 (HHV-8). HHV-8 has been found in > 90% of AIDS-KS tumors, as well as in classic KS, endemic African KS, and post–organ transplant-related KS. It has also been identified in body cavity–based lymphoma/primary effusion lymphoma, multicentric Castleman’s disease, and angio-immunoblastic lymphadenopathy with dysproteinemia (AILD) in HIV-infected patients.
HHV-8 may be transmitted through sexual contact, blood products, or organ transplantation. The seroprevalence of HHV-8 in AIDS-related KS is nearly 100%. HHV-8 has been found in high concentration in the saliva of patients with KS.
HHV-8 is critical in the pathogenesis of AIDS-related KS. The mechanism by which HHV-8 induces KS in susceptible individuals is the subject of intense current investigations.
Environmental and host factors
Various environmental and host factors, including HIV- and HHV-8–induced cytokines, AIDS-associated infections, the host’s hormonal milieu, immunosuppression, and antiretroviral therapy, may induce or suppress the development of KS and alter its growth.
Franceschi S, Maso LD, Rickenbach M, et al: Kaposi sarcoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy. Br J Cancer 99:800–804, 2008.
O’Mahony D, Gandjbakche A, Hassan M, et al: Imaging techniques for Kaposi’s sarcoma. J HIV Ther 13:65–71, 2008.
Spano JP, Costagliola D, Katlama C, et al: AIDS-related malignancies: State of the art and therapeutic challenges. J Clin Oncol 26:4834–4842, 2008.
Sullivan RJ, Pantanowitz L, Casper C, et al: HIV/AIDS: Epidemiology, pathophysiology and treatment of Kaposi sarcoma-associated herpes virus disease: Kaposi sarcoma, primary effusion lymphoma, and multicentric Castleman disease. Clin Infect Dis 47:1209–1215, 2008.
Sullivan RJ, Pantanowitz L, Dezube BJ: Targeted therapy for Kaposi’s sarcoma. BioDrugs 23:69–75, 2009.
Lewden C, May T, Rosenthal E, et al: Changes in causes of death among adults infected by HIV between 2000 and 2005: The “Mortalite 2000 and 2005” surveys (ANRS EN19 and Mortavic). J Acquir Immune Defic Synd 48:590–598, 2008.
Levine A, Lee J, Kaplan L, et al: Efficacy and toxicity of concurrent rituximab plus infusional EPOCH in HIV-associated lymphoma: AIDS Malignancy Consortium Trial 034. J Clin Oncol 26:8527, 2008.
Lin L, Lee JY, Kaplan LD, et al: Effects of chemotherapy in AIDS-associated non-Hodgkin’s lymphoma on Kaposi’s sarcoma herpes virus DNA in blood. J Clin Onc 27:2496–2502, 2009.
Marti-Carvajal AJ, Cardona AF, Lawrence A: Interventions for previously untreated patients with AIDS-associated non-Hodgkin’s lymphoma. Cochrane Database Syst Rev 8:CD005419, 2009.
Mwanda WO, Orem J, Fu P, et al: Dose-modified oral chemotherapy in the treatment of AIDS-related non-Hodgkin’s lymphoma in East Africa. J Clin Onc 27:3480–3488, 2009.
Re A, Michieli M, Casari S, et al: High-dose therapy and autologous peripheral blood stem cell transplantation as salvage treatment for AIDS-related lymphoma: Long-term results of the Italian Cooperative Group on AIDS and Tumors (GICAT) study with analysis of prognostic factors. Blood 114:1306–1313, 2009.
On Cervical and anal Carcinomas
Chaturvedi AK, Madeleine MM, Biggar RJ, et al: Risk of human papillomavirus-associated cancers among persons with AIDS. J Natl Cancer Inst 101:1120–1130, 2009.
Cranston RD, Hirschowitz SL, Cortina G, et al: A retrospective clinical study of the treatment of high-grade anal dysplasia by infrared coagulation in a population of HIV-positive men who have sex with men. Int J STD AIDS 19:118–120, 2008.
De Vuyst H, Clifford GM, Nascimento MC, et al: Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: A meta-analysis. Int J Cancer 124:1626–1636, 2009.
Seo Y, Kinsella MT, Reynolds HL, et al: Outcomes of chemoradiotherapy with 5-Fluorouricil and mitomycin C for anal cancer in immunocompetent versus immunodeficient patients. Int J Radiat Oncol Biol Phys 75:143–149, 2009.
Stier EA, Goldstone SE, Berry JM, et al: Infrared coagulator treatment of high-grade anal dysplasia in HIV-infected individuals: An AIDS malignancy consortium pilot study. J Acquir Immune Defic Syndr 47:56–61, 2008.
on non-aids-defining malignancies
Crum-Cianflone N, Hullsiek KH, Marconi V, et al: Trends in the incidence of cancers among HIV-infected persons and the impact of antiretroviral therapy: A 20-year cohort study. AIDS 23:41–50, 2009.
Deeken JF, Pantanowitz L, Dezube BJ: Targeted therapies to treat non-AIDS defining cancers in patients with HIV on HAART therapy: Treatment considerations and research outlook. Curr Opin Oncol 21:445–454, 2009.
Hakimian R, Fang H, Thomas L, et al: Lung cancer in HIV-infected patients in the era of highly active antiretroviral therapy. J Thorac Oncol 2:268–272, 2007.
Monforte A, Abrams D, Pradier C, et al: HIV-induced immunodeficiency and mortality from AIDS-defining and non-AIDS defining malignancies. AIDS 22:2143–2153, 2008.
Powles T, Robinson D, Stebbing J, et al: Highly active antiretroviral therapy and the incidence of non-AIDS-defining cancers in people with HIV infection. J Clin Oncol 27:884–890, 2009.
Abbreviations in this chapter:
ACTG = AIDS Clinical Trials Group; AMC = AIDS Malignancy Consortium; ANRS = Agence Nationale de Recherche sur le Sida et les Hépatites Virales; FIGO = International Federation of Gynecology and Obstetrics; SEER = Surveillance, Epidemiology and End Results
Acknowledgment: Supported, in part, by grants from the California HIV/AIDS Research Program, the UCLA Network for AIDS Research in Los Angeles (MC08-LA-710) and USPHS, NIH grants AI-69424, AI28697, CA-121947, and RR00865.