Acquired Immunodeficiency Syndrome and Cancer
Summary of Key Points
Incidence
• Non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), Kaposi sarcoma (KS), cervical cancer, and anal cancer all occur with increased incidence in patients infected with the human immunodeficiency virus (HIV). NHL, KS, and cervical cancer are acquired immunodeficiency syndrome (AIDS) defining.
• KS occurs in HIV-infected patients who also are infected with KS-associated herpesvirus. Outside of Africa and in some Mediterranean populations, KS occurs mainly in men who have sex with men.
• Lymphoma (non-Hodgkin and Hodgkin) occurs in all HIV risk groups. These neoplasms tend to be aggressive and extranodal and manifest at an advanced stage. Burkitt lymphoma and HL tend to occur in patients with higher CD4 counts (typically greater than 200 cells/µL), whereas primary central nervous system lymphoma tends to occur in patients with very low CD4 counts (typically less than 50/mm3).
Etiology and Pathogenesis
• KS is always associated with KS-associated herpesvirus; immunocompromise, inflammatory cytokines, and perhaps the HIV TaT protein contribute to pathogenesis.
• Lymphoma in HIV-infected patients is associated with Epstein-Barr virus (EBV) in approximately half of the cases; immunocompromise, chronic antigen stimulation, and perhaps inflammatory cytokines and chemokines contribute to pathogenesis.
• Cervical and anal cancer require the oncogenic strains of human papilloma virus. The pathogenesis of these two cancers is remarkably similar.
Kaposi Sarcoma
• A biopsy is indicated to confirm diagnosis.
• A computed tomography (CT) scan of the chest and abdomen is also indicated.
• Gastrointestinal endoscopy is performed if clinically indicated.
• Highly active antiretroviral therapy (HAART) and treatment of opportunistic infections sometimes are associated with regression of KS.
• If disease is symptomatic or rapidly progressive, or with visceral involvement, systemic therapy with liposomal anthracycline or paclitaxel is instituted; all patients should receive pneumocystis prophylaxis. Hematopoietic growth factors, antifungal treatment, and antiherpesvirus prophylaxis or treatment also are appropriate for most patients receiving cytotoxic chemotherapy.
• If disease is indolent and antiretroviral therapy has just been initiated or major changes have been made, observation may be appropriate.
• For a few lesions, topical therapy, injection of lesions, or radiation therapy may be adequate treatment.
• For persons with systemic disease, consider interferon, thalidomide, or experimental therapy.
Non-Hodgkin Lymphoma
• Signs and symptoms of tumor lysis.
• Extent of disease can be determined with use of CT and bone marrow biopsy in most cases.
• Extranodal and atypical presentations of lymphoma are common, as are constitutional symptoms (especially with HL).
• Positron emission tomography scans with fluorodeoxyglucose labeling should be interpreted with extreme caution because HIV infection, inflammation associated with opportunistic infection, and immune reconstitution syndrome all are associated with fluorodeoxyglucose activity.
• Chemotherapy (with cyclophosphamide, hydroxydaunomycin [doxorubicin], vincristine [Oncovin], and prednisone [CHOP] plus rituximab or etoposide, Oncovin, doxorubicin, cyclophosphamide, and prednisone [EPOCH] plus rituximab) is used to treat NHL.
• Intrathecal prophylaxis is appropriate for patients with Burkitt lymphoma or Burkitt-like lymphoma, for patients with bone marrow involvement of NHL, and for patients with EBV-associated NHL. Either cytarabine or methotrexate can be used for this purpose.
• Patients with relapsed lymphoma may be appropriate candidates for high-dose therapy with stem cell rescue.
Hodgkin Lymphoma
• HIV-associated classic HL occurs in patients with higher CD4 counts. It is 80% to 100% associated with EBV. Patients are seen with more advanced disease and more aggressive histologies (mixed cellularity and lymphocyte-depleted HL).
• Staging and evaluation are similar to that for NHL.
• Treatment with doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) results in an overall survival rate at 5 years of 75% (15% below that of the non-HIV population).
Cervical Cancer
• Prevention of invasive disease by screening for and treatment of preinvasive disease is the mainstay in the developed world.
• Staging requires both visualization of the cervical area and CT scanning.
• Treatment depends heavily on the extent of disease because it varies from colposcopic therapies to surgery alone or in combination with radiation and chemotherapy.
• Early stages are treated with curative intent.
• Distantly metastatic disease is largely treated for palliation.
Anal Cancer
• Prevention of invasive disease by screening for and treatment of preinvasive disease is an active area of research because the progression rates are under investigation.
• Staging requires both visualization of the anal area and CT scanning.
• Treatment of preinvasive lesions varies among practitioners and is an active area of investigation.
• Treatment depends heavily on the extent of disease because it varies from local therapies to surgery alone or in combination with radiation and chemotherapy.
• Early stages are treated with curative intent.
• Distantly metastatic disease is largely treated for palliation, although some patients with only local nodal metastases may be cured.
Hepatocellular Carcinoma
• Hepatitis B and C virus promote hepatocellular cancer. HIV infection dramatically accelerates this process, although hepatocellular cancer is not an AIDS-defining cancer.
• Early-stage disease is amenable to curative resection or possibly liver transplantation. For larger tumors, multiple tumors, or extrahepatic metastases, systemic chemotherapy is required. Specific approaches in the setting of HIV have not been studied.
Cytotoxic Therapy for Cancer
• Pneumocystis prophylaxis is given regardless of the CD4 count.
• Other prophylaxis for bacteria, fungi, herpes viruses, and mycobacterium depend on the regimen and level of preexisting immunosuppression.
• In HAART-naive patients, antiretroviral therapy should typically be initiated shortly after cytotoxic chemotherapy begins and when associated nausea is controlled.
1. All of the following are acquired immunodeficiency syndrome (AIDS)-defining diagnoses except:
2. True or false: In the highly active antiretroviral therapy (HAART) era, people living with HIV are no longer at increased risk for lymphoma.
3. Kaposi sarcoma in the setting of HIV is dependent on all of the following except:
A Human herpesvirus-8, also called the Kaposi sarcoma virus infection of skin cells
4. All of the following are true about cervical cancer in HIV-positive women except:
A Cervical cancer is preventable in large part with screening for early lesions.
B Persistence of human papillomavirus (HPV) is higher among HIV-positive women compared with the general population.
C The oncogenic subtypes HPV 16 and 18 are the most commonly associated with cancer.
D HPV vaccination has been proven to be efficacious in both the general population and HIV-positive women.
5. True or false: Screening for anal cancer and treating preinvasive lesions has been proven to have benefit in randomized studies in persons living with HIV.
1. Answer: C. Hodgkin lymphoma is not an AIDS-defining cancer; despite the marked increase in prevalence, it is not included in the Centers for Disease Control and Prevention definition of AIDS. Similarly, anal cancer is also not an AIDS-defining condition. Both of these are technically human immunodeficiency virus (HIV)-associated malignancies, but technically they are not AIDS-defining. These definitional issues reflect the historical definitions of AIDS more than the biology of the malignancies in the context of HIV.
2. Answer: B. The risk is still markedly elevated, although certain subtypes such as central nervous system (CNS) lymphoma are largely confined to people with a CD4 count less than 50.
3. Answer: A. The virus invades endothelial cells. All of the other components interplay to create Kaposi sarcoma conditions.
4. Answer: D. The HPV vaccine is safe and efficacious in the general population. Studies in HIV-positive women are ongoing.
5. Answer: B. Randomized trials have not been performed. However, the biology is analogous to cervical cancer, where the institution of Papanicolaou smear screening dramatically reduced the incidence of invasive and advanced cervical cancer and associated deaths in the developing world.
