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The Oncologist, Vol. 3, No. 4, 279-283, August 1998
© 1998 AlphaMed Press

Physician Education

AIDS-Related Malignancies

G. Michael Wool

Los Angeles, California, USA

Correspondence: G. Michael Wool, M.D., 2080 Century Park East, Suite 1006, Los Angeles, California 90067, USA. Telephone: 310-556-7991; Fax: 310-556-8464; e-mail: mwool{at}ucla.edu


   Overview of Malignancy in Patients with Aids
Top
 Overview of Malignancy in...
Kaposi's Sarcoma
 Lymphomas
 Other Tumors in HIV-Infected...
 Conclusions
 References
 
Despite the advent of highly active antiretroviral therapy, the incidence of human immunodeficiency virus (HIV)-associated malignancies has not decreased. The United States Centers for Disease Control (CDC) has determined that Kaposi's sarcoma, non-Hodgkin's lymphoma (including primary central nervous system lymphoma), and cervical carcinoma define the acquired immune deficiency syndrome (AIDS). Some literature reports include Hodgkin's disease, anal carcinoma, lung cancer, and non-melanomatous skin cancers as ones commonly found in people infected with HIV [1, 2]. The oncologist is further challenged treating a patient with malignancy whose malignancy is complicated by a concurrent compromised marrow function. This article will review the clinical presentation and current treatment for the HIV-associated malignancies and selected other tumors in the HIV-infected patient. Furthermore, HIV-associated myelosuppression is a common problem in antiviral-undertreated or antiviral-resistant patients.


   Kaposi's Sarcoma
Top
 Overview of Malignancy in...
 Kaposi's Sarcoma
Lymphomas
 Other Tumors in HIV-Infected...
 Conclusions
 References
 
Kaposi's sarcoma was once uncommon, seen primarily in the indolent form in elderly men of Mediterranean or Jewish descent [3]. An aggressive form of Kaposi's sarcoma is now common in nearly one-third of patients with AIDS [4, 5]. An infectious agent is thought to have a role in the etiology of Kaposi's sarcoma [6].

The lesions associated with Kaposi's sarcoma may be the first notable manifestation of AIDS; however, the clinical manifestations and disease course are variable. Some HIV-infected patients with AIDS may initially have the indolent form. As barely elevated pink or red plaques that can be round or oval, they first appear primarily on the extremities or mucosa. They may eventually widely disseminate on the skin, and can be associated with visceral lesions and disseminated lymph node involvement (Fig. 1Go). Kaposi's sarcoma lesions contain multiple cellular contents: proliferating endothelial cells, fibroblasts, infiltrating leukocytes, and spindle-shaped tumor cells [7].





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  		Figure 1. (A) Advanced Kaposi's sarcoma causing pain and precluding hygiene. (Courtesy of Burton Anderson, M.D., University of Illinois at Chicago). (B) Close-up of Kaposi's sarcoma on skin. (Courtesy National Cancer Institute, Bethesda, Maryland). (C) Kaposi's sarcoma on the foot of a 34-year-old male, showing large, confluent, partially ulcerated plaques and nodules. (Courtesy of the Slide Atlas of Pathology of AIDS; used with permission).

 
Most patients with AIDS and Kaposi's sarcoma do not die as a result of the tumors, but, rather, die of opportunistic infections. Sometimes, Kaposi's sarcoma is the proximate cause of death, usually when it is due to pulmonary or other visceral organ involvement (Table 1).


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  		Table 1. Kaposi's sarcoma in AIDS and clinical manifestations of Kaposi's sarcoma in AIDS
 
There is no set recommendation for the treatment of Kaposi's sarcoma of AIDS, mainly because of the varied presentation of the disease and rate of disease progression. Patients with limited cutaneous disease and no evidence of visceral involvement may do well with local treatments of radiation or intralesional injections of sclerosing agents; liquid nitrogen cryotherapy, excision, electrocauterization/laser surgery, photodynamic therapy, or topical retinoids may be used [8, 9]. Systemic treatment of AIDS-related Kaposi's sarcoma includes interferons, paclitaxel, human chorionic gonadotropin, vinca alkaloids, and antiangiogenesis agents. For patients with more than 200 CD4+ cells/µl, interferon-{alpha} is often the best treatment [10]. Recombinant human interferon-{alpha} is the only biologic agent approved for treatment of Kaposi's sarcoma in patients with AIDS.

There are several chemotherapy drugs with activity against Kaposi's sarcoma (Table 2). Vinblastine is a good therapeutic option as it does not cause significant myelosuppression. Zidovudine and interferon-{alpha} have been shown to increase the overall response rates of the tumors; however, this drug combination has major dose-limiting toxicities of anemia and neutropenia from the use of interferon-{alpha} [11].


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  		Table 2. Chemotherapy agents useful in the treatment of Kaposi's sarcoma of AIDS. Adapted from [52].
 
As there is no cure for Kaposi's sarcoma, use of palliative therapies must be balanced against quality of life and toxicity.


   Lymphomas
Top
 Overview of Malignancy in...
 Kaposi's Sarcoma
 Lymphomas
Other Tumors in HIV-Infected...
 Conclusions
 References
 
Lymphoma is a relatively late manifestation of HIV infection, and HIV in itself may be an indirect cause of AIDS-related lymphomas. HIV can induce the expression of a number of inflammatory cytokines, such as interleukin (IL)-6 and IL-10, associated with the proliferation, stimulation, and activation of B lymphocytes.

Non-Hodgkin's lymphoma is the second most common malignancy associated with HIV infection, with 3% to 5% of patients presenting with non-Hodgkin's lymphoma as their first manifestation of AIDS [21]. There are a variety of clinical manifestations, but many patients present with asymptomatic adenopathy involving cervical or inguinal regions, or both. Most AIDS patients with non-Hodgkin's lymphoma have B-cell immunoblastic lymphoma, and many have extranodal disease [22].

Primary, central nervous system lymphoma in HIV-infected patients is also common and is generally the aggressive, large-cell type. All these patients will test positive for integrated Epstein-Barr virus genomes and most will have detectable Epstein-Barr virus in their cerebrospinal fluid [23-25].

Treating AIDS patients who have lymphoma is of concern because even standard-dose chemotherapy can further compromise their immune functions. Treatment usually consists of highly myelosuppressive chemotherapy, including use of several of the following drugs: anthracyclines, cyclophosphamide, vinca alkaloids, methotrexate, and corticosteroids (Table 3). Radiation therapy is the major treatment for primary central nervous system lymphoma and is sometimes successful in treating bulky tumor masses or central nervous system involvement. Whole-brain irradiation has been shown to improve survival in HIV-infected patients [26]. Hodgkin's lymphoma does respond to chemotherapy; regimens used in HIV-infected patients are the same as those used in non-HIV-infected patients (Table 3).


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  		Table 3. Chemotherapy treatment of non-Hodgkin's lymphoma and Hodgkin's disease of AIDS
 
As with Kaposi's sarcoma, selecting the optimal therapy must take into account the patient's overall prognosis, quality of life, and general clinical condition. Palliative therapy may be more appropriate in patients with advanced disease.


   Other Tumors in HIV-Infected Patients
Top
 Overview of Malignancy in...
 Kaposi's Sarcoma
 Lymphomas
 Other Tumors in HIV-Infected...
Conclusions
 References
 
When AIDS was first identified in the United States in homosexual men, Kaposi's sarcoma was the only cancer listed among the initial AIDS-defining illnesses. Since that time, the HIV epidemic has spread to other populations, and infected people are living longer. These factors have led to the identification of many more HIV-related cancers.

Invasive cervical cancer was added to the AIDS case definition because studies of HIV-infected women showed an increased prevalence of cervical dysplasia [32]. There is, however, little epidemiologic evidence that there is a higher incidence of invasive cervical cancer in HIV-infected women [33, 34]. Cervical carcinoma is currently the only AIDS-defining malignancy that is able to be detected and treated early in its course, and cytologic screening for early preinvasive malignant anal lesions and neoplasia is being studied [35]. Because a virus called human papillomavirus (HPV) is strongly associated with cervical dysplasia and because this virus is often spread sexually, it may be the causative agent for the cervical abnormalities.

As is the case with cervical cancer, the association between anal cancer and HIV infection has been partly confounded by sexual behavior; and, as with cervical cancer, few studies have shown an increase among HIV-infected adult men. A study did show that HIV-infected homosexual men have a greater risk of anal cancer with decreasing CD4+ cell counts [36]. Although HPV is presumed to have a role in anal neoplasia, as it does in cervical neoplasia [37], routine screening and treatment for anal dysplasia is not currently standard of practice.

Other cancers have been reported in HIV-infected individuals, usually ones with advanced HIV disease. These include testicular cancer [38-42], lung cancer [43-47], head and neck cancer, and basal cell carcinoma and leukemia [48, 49].

Patients with HIV infection and other malignancies are usually treated with the same regimens as non-HIV-infected patients with cancer. Unfortunately, many of the most effective anti-neoplastic agents (doxorubicin, cyclophosphamide, methotrexate, etc.) are highly myelosuppressive.


   Conclusions
Top
 Overview of Malignancy in...
 Kaposi's Sarcoma
 Lymphomas
 Other Tumors in HIV-Infected...
 Conclusions
References
 
Chemotherapy is useful in inducing tumor regression and improving survival in all patients, including those with advance-stage, AIDS-related malignancies; however, most chemotherapeutic regimens, as noted earlier, can cause significant myelosuppression in these already-immunocompromised patients. Also, the drugs used directly to treat HIV infection, ganciclovir, zidovudine, and trimethoprim-sulfamethoxazole, are known to be myelosuppressive [11, 50-52]. At the XII International AIDS Conference held in Geneva, Switzerland in July 1998, it was reported that more than 15 antiretroviral agents were either FDA-approved for marketing or under investigation in large-scale clinical trials. While combination therapy has improved morbidity and mortality, HIV-associated malignancies and their successful treatment remain a challenge. Myelosuppressive chemotherapy in conjunction with emerging antiviral combinations are a consideration in the overall HIV therapy. These offer challenges to the oncologist treating AIDS and HIV-infected patients.


   Acknowledgments
 
The author wishes to thank Robbie Wong, Ph.D., and Stephen C. Verral, MPH, for their assistance in the preparation of this manuscript.


   References
Top
 Overview of Malignancy in...
 Kaposi's Sarcoma
 Lymphomas
 Other Tumors in HIV-Infected...
 Conclusions
 References
 

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