AIDS-Related Cancers

AIDS-related cancers

Definition

The AIDS-related cancers are a group of cancers that occur more frequently in persons with human immunodeficiency virus (HIV) infection than in the general population. The most common form of AIDS-related cancer, Kaposi's sarcoma (KS), was one of the first indications of the AIDS epidemic in the early 1980s. While the number of new cases of KS has been declining in recent years, the number of AIDS-related lymphomas has been increasing at a rate of 2% to 3% each year.

Description

In order to understand the causes and treatment of AIDS-related cancers, it is useful to begin with a basic description of HIV infection. AIDS, or acquired immunodeficiency syndrome, is a disease of the immune system that is caused by HIV. HIV is a retrovirus, a single-stranded virus containing ribonucleic acid (RNA) and an enzyme called reverse transcriptase. This enzyme enables the retrovirus to make its genetic material part of the DNA in the cells that it invades. HIV selectively infects and destroys certain subtypes of white blood cells called CD4 cells, which are an important part of the body's immune system. As an infected person's number of CD4 cells drops, he or she is at risk of developing opportunistic infections, disorders of the nervous system, or an AIDS-related cancer. HIV is transmitted through blood or blood products that enter the bloodstream— most commonly through sexual contact or contaminated hypodermic needles.

Kaposi's sarcoma

Kaposi's sarcoma is the most common type of cancer related to HIV infection. About 20% of patients diagnosed with AIDS will eventually develop KS. There are two other major subtypes of KS—so-called classic KS and African KS—with different causes that are not yet well understood. AIDS-related KS (also called epidemic KS) is characterized by purplish or brownish lesions (areas of diseased or injured tissue) on the skin, in the mouth, or in the internal organs. The lesions may take the form of small patches or lumps (nodular lesions), large patches that grow downward under the skin (infiltrating lesions), or lumpy swellings in the lymph nodes. Unlike other cancers that typically develop in one organ or area of the body, KS often appears simultaneously in many different parts of the body. It may be the first indication that the patient has AIDS.

Non-Hodgkin's lymphoma

Lymphomas are cancers of the immune system that develop when white blood cells called lymphocytes begin to grow and multiply abnormally. The increased numbers of lymphocytes cause the lymph nodes, the organs that produce these white blood cells, to swell and form large lumps that can be felt. Lymphomas are divided into two large categories: those that are related to Hodgkin's disease (HD), and non-Hodgkin's lymphoma (NHL). HD can be differentiated from NHL by the presence of Reed-Sternberg cells in the lymphatic tissue; these cells are not found in any other type of cancer.

Non-Hodgkin's lymphoma, or NHL, occurs more often than Hodgkin's disease; about 50, 000 new cases are diagnosed annually in the United States. They may involve the spleen, liver, bone marrow, or digestive tract as well as the lymph nodes. Three important types of NHL are related to AIDS:

• Primary central nervous system lymphomas (PCNSL). This type accounts for about 20% of NHL cancers found in AIDS patients, but only 1% to 2% of NHL cancers in patients not infected by HIV. Lymphomas of this type start in the brain or the spinal cord. Their symptoms include headaches, paralysis, seizures, and changes in the patient's mental condition. Patients diagnosed with PCNSL are more likely to suffer from advanced HIV infection than patients with other types of NHL.
• Systemic lymphomas. These are also called peripheral lymphomas. They begin in the lymph nodes or other parts of the lymphatic system and may spread throughout the body. Burkitt's lymphoma (BL) is a type of systemic lymphoma that is one thousand times more common in AIDS patients than in the general population.
• Primary effusion lymphomas, also called body cavity-based lymphomas (BCBL). This type of NHL is relatively rare, but seems to be related to infection by human herpesvirus 8 (HHV-8) in addition to HIV.

HIV-associated Hodgkin's disease

The symptoms of Hodgkin's disease include painless swelling of the lymph nodes of the neck, groin, and armpits; itching ; night sweats ; weight loss ; and fever . While one study has indicated that HIV-positive gay men have a higher risk of developing Hodgkin's disease as well as non-Hodgkins lymphomas, the Centers for Disease Control and Prevention (CDC) has not defined Hodgkin's disease as an AIDS-related cancer as of early 2001. Hodgkin's disease appears to occur more frequently in HIV-positive intravenous drug users, however, than in other persons with HIV infection.

Cervical and anal cancers

In women, cancer of the cervix (the lower end of the uterus or womb) is more likely to occur in HIV-infected individuals than in the general female population. About 60% of women with HIV infection are found to have some kind of abnormal tissue growth or cell formation in the cervix when a Pap test is performed. The human papilloma virus (HPV) is thought to be a co-factor in the development of cervical cancers. Papilloma viruses are a group of tumor-causing viruses that also cause genital warts. Cervical cancers develop more rapidly in HIV-positive than in HIV-negative women, are harder to cure, and are more likely to recur.

Cancers of the anus represent less than 1% to 2% of cancers of the large bowel. There are about 10, 000 cases of anal cancer annually in the United States. The high rates of occurrence of this type of cancer in gay men may be related more closely to the presence of HPV and to the practice of anal intercourse than to HIV infection by itself.

Other AIDS-associated cancers

Other cancers linked to HIV infection include testicular cancer , cancers of the mouth, and a type of cancer of the bone marrow called multiple myeloma . Some other cancers, including breast cancer , lung cancer, andmelanoma (a type of skin cancer), are thought to occur more frequently among people with AIDS even though they are not identified as AIDS-associated cancers in the strict sense.

Demographics

The demographic distribution of AIDS-related cancers varies somewhat depending on the type of cancer. Epidemic KS is about 10 times more common among gay men than among members of other groups at risk for AIDS (hemophiliacs, intravenous drug users, etc.); it affects men eight times as frequently as women. AIDS-related Hodgkin's disease occurs more frequently among intravenous drug users. By contrast, AIDS-related lymphomas occur with equal frequency in members of all risk groups—including the children of persons with HIV infection.

Causes

The most common types of AIDS-related cancers have been linked to oncogenic (tumor-causing) viruses:

• Human herpesvirus 8 (HHV-8) is associated with KS and some of the less common types of AIDS-related lymphomas (ie. cancers of the lymphatic system).
• Epstein-Barr virus (EBV) is associated with the more common types of AIDS-related lymphomas, particularly PCNSL and Burkitt's lymphoma.
• Human papillomavirus (HPV) is associated with anal cancer and with cervical cancer in women.

Oncogenic viruses cause cancer by changing the genetic material inside tissue cells. When this genetic material is changed, the cells begin to grow and multiply uncontrollably. The abnormal tissue formed by this uncontrolled growth is called a tumor. A healthy human immune system has a greater ability to protect the body against oncogenic viruses and to stop or slow down tumor formation. Since the retrovirus that causes AIDS weakens the immune system, persons with AIDS are at greater risk of developing cancers caused by oncogenic viruses.

Some types of AIDS-related cancers, such as Burkitt's lymphoma, have been linked to changes in human chromosomes (translocations). In a translocation, a gene or group of genes moves from one chromosome to another. Burkitt's lymphoma is associated with exchanges of genetic material between chromosomes 8 and 14 or between chromosomes 2 and 22.

Special concerns

An important special concern for patients with AIDS-related cancers is the difficulty of combining cancer treatment—especially chemotherapy—with treatment for HIV infection. Since 1996, the standard treatment for AIDS is highly active antiretroviral therapy (HAART). HAART is a combination drug therapy involving three or four different medications. Because of the powerful side effects of these drugs, patients with AIDS-related cancers are usually put on low-dose chemotherapy for the cancer. The chemotherapy, however, increases the patient's risk of developing an AIDS-related infection, such as thrush or Pneumocystis carinii pneumonia (PCP).

Another special concern for patients with AIDS-related cancers is fear of rejection by friends and loved ones. Although the moral stigma attached to HIV infection is not as strong as it was at the beginning of the epidemic, some patients may still fear condemnation by others. Most hospitals have chaplains or spiritual counselors who can help patients with these concerns or put them in touch with someone from their own spiritual tradition.

Treatments

The different types of AIDS-related cancers have different treatment considerations.

Kaposi's sarcoma

KS differs from other solid tumors in that it lacks a stage or site of origin in which it can be cured. In addition, there is no relationship between the stage of KS and its response to treatment. Many doctors treat early KS with chemotherapy injections or treat localized lesions with radiation therapy rather than give the patient systemic chemotherapy. In 1999, the FDA approved alitretinoin (Panretin) gel as a topical treatment for KS. When systemic chemotherapy is used, the standard regimens are a combination of vinblastine (Velban) and vincristine (Oncovin) on a weekly schedule, or a combination of doxorubicin , bleomycin , and vincristine given every week. Surgery is not often used in the treatment of KS.

Non-Hodgkin's lymphoma

Patients with early, slow-growing forms of NHL are usually treated with radiation. The later stages of slow-growing non-Hodgkin's lymphomas may be treated with chemotherapy (single-agent or combination), or with a combination of radiation and chemotherapy. Common treatments for more aggressive AIDS-related lymphomas are the combination chemotherapy regimens known as CHOP (cyclophosphamide , doxorubicin, vincristine, and prednisone) or m-BACOD (intermediatedose methotrexate , bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone ). In general, AIDS-related lymphomas are more aggressive than non-HIV-related lymphomas and do not respond as well to chemotherapy. PCNSL is usually treated with radiation therapy alone because most chemotherapy drugs cannot cross the blood-brain barrier and enter the central nervous system.

Newer forms of treatment for non-Hodgkin's lymphomas include bone marrow and stem cell transplants and immunotherapy with the use of monoclonal antibodies (MABs). MABs are antibodies produced by cloned mouse cells grown in a laboratory. They target cancer cells and bind to them, alerting cells of the immune system to destroy the abnormal cells. MABs are sometimes given together with chemotherapy.

HIV-associated Hodgkin's disease

HIV-associated Hodgkin's disease is usually treated with chemotherapy but does not respond as well to treatment as non-HIV-related Hodgkin's disease. Patients being treated with antiretroviral therapy may need to have it modified during a course of chemotherapy for Hodgkin's disease.

Cervical and anal cancers

Cervical and anal cancers are treated in the early stages with a combination of surgery and radiation. Larger or later-stage tumors are treated with chemotherapy (mitomycin or cisplatin and fluorouracil ) in addition to surgery and radiation treatment.

Alternative and complementary therapies

In the early years of the AIDS epidemic, a variety of alternative approaches were used to treat the internal forms of KS as well as the external skin lesions: homeopathic preparations of periwinkle, poke root (phytolacca), and mistletoe; a mixture of selenium, aloe vera gel, and silica; Chinese patent medicines; periodic three-to seven-day grape fasts as part of an overall vegetarian diet; and castor oil packs.

The only alternative treatment for KS that has been evaluated by the National Institutes of Health (NIH) is shark cartilage. Shark cartilage products are widely available in the United States as over-the-counter (OTC) preparations. The use of shark cartilage to treat KS derives from a popular belief that sharks and other cartilaginous fish (skates and rays) do not get cancer. This therapy, however, has not been proven to be effective.

Other alternative treatments for AIDS-related KS include:

• Naturopathic remedies. High doses of vitamin C, zinc, echinacea, or goldenseal to improve immune function; or preparations of astragalis, osha root, or licorice to suppress the HIV virus.
• Homeopathic remedies. These include a homeopathic preparation of cyclosporine and another made from a dilution of killed typhoid virus.
• Ozone therapy.

With regard to other categories of AIDS-related cancers, there have been reports of using hydrazine sulfate or laetrile to treat AIDS-related lymphomas. Some researchers in Germany are investigating mistletoe extracts as a treatment for AIDS-related cancers in women.

Complementary therapies are used in the treatment of AIDS-related cancers to help patients keep up their will to live; to cope with such side effects as depression , nausea caused by chemotherapy, concerns about disfigurement, and fear of rejection; and to gain comfort from supportive social groups. Specific complementary approaches that have been recommended for cancer patients include acupuncture, creative visualization, pet therapy, meditation, prayer, yoga, Reiki, aromatherapy, and some herbal remedies (St. John's wort for depression, peppermint or spearmint tea for nausea).

Clinical trials

As of early 2001, 39 clinical trials of treatments for AIDS-related lymphomas, 13 trials of treatment for KS, and 13 trials of treatments for PCNSL were being conducted in the United States. Thalidomide , a drug that made headlines in the 1960s for its role in causing birth defects, was shown to be effective in treating KS in July 2000. It is undergoing further study as of 2001.

See Also Immunologic therapies

Resources

BOOKS

Dollinger, Malin, Ernest H. Rosenbaum, and Greg Cable. Cancer Therapy. Kansas City, MO: Andrews and McMeel, 1994.

"Hematology and Oncology." Section 11 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers and Robert Berkow. Whitehouse Station, NJ: Merck Research Laboratories, 1999.

The Burton Goldberg Group. Alternative Medicine: The Definitive Guide. Fife, WA: Future Medicine Publishing, Inc., 1995.

PERIODICALS

San Francisco AIDS Foundation. Bulletin of Experimental Treatments for AIDS.

ORGANIZATIONS

AIDS Clinical Trials Group (ACTG). c/o William Duncan, Ph.D., National Institutes of Health. 6003 Executive Boulevard, Room 2A07, Bethesda, MD 20892.

American Cancer Society (ACS). 1599 Clifton Road, NE, Atlanta, GA 30329. (404) 320-3333 or (800) ACS-2345. Fax: (404) 329-7530. <http://www.cancer.org>.

National Cancer Institute, Office of Cancer Communications.31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. (800) 4-CANCER. TTY: (800) 332-8615. <http://www.nci.nih.gov>.

National Institutes of Health National Center for Complementary and Alternative Medicine (NCCAM) Clearinghouse. PO Box 8218, Silver Spring, MD 20907-8218. (888) 644-6226. TTY/TDY: (888) 644-6226. Fax: (301) 495-4957. <http://nccam.nih.gov>.

San Francisco AIDS Foundation (SFAF). 995 Market Street, #200, San Francisco, CA 94103. (415) 487-3000 or (800) 367-AIDS. Fax: (415) 487-3009. <http://www.sfaf.org>.

OTHER

<http://www.hivchannel.com>.

<http://www.oncologychannel.com>.

The Body: An AIDS and HIV Information Resource. <http://www.thebody.com>.

WEB SITES WITH INFORMATION IN SPANISH

Cancer Care. <http://www.cancercareinc.org>.

New York Online Access to Health (NOAH). <http://www.noah.cuny.edu>.

Rebecca J. Frey, Ph.D.

KEY TERMS

Blood-brain barrier

—A layer of tightly packed cells in the small blood vessels in the brain that prevent many medications and other substances from entering the brain.

Burkitt's lymphoma

—A subtype of non-Hodgkin's lymphoma that is one thousand times more common in AIDS patients than in the general population.

Highly active antiretroviral therapy (HAART)

—A combination drug therapy for AIDS, usually consisting of three or more medications.

Human herpesvirus (HHV)

—A family of viruses that contain DNA and cause a number of diseases, including chickenpox, shingles, and genital herpes.

Human papilloma virus (HPV)

—A type of tumor-causing virus that causes genital warts and is associated with AIDS-related cervical cancers in women.

Kaposi's sarcoma (KS)

—The most common type of AIDS-related cancer. KS is characterized by purplish or brownish spots on the skin and may spread to the internal organs.

Lymphatic system

—The system of glands, tissues, and vessels in the body that produces lymphocytes and circulates them through the body in a clear, yellowish fluid called lymph.

Lymphocyte

—A type of white blood cell involved in the production of antibodies.

Non-Hodgkins lymphoma (NHL)

—A type of cancer of the immune system that is the second most common form of AIDS-related cancer. It is sometimes called AIDS-related lymphoma.

Oncogenic

—Producing or causing tumors. The most common types of AIDS-related cancers are associated with oncogenic viruses.

Monoclonal antibody

—An antibody produced in the laboratory from a cloned cell rather than in the body.

Retrovirus

—A virus that contains a single strand of RNA and a unique enzyme called reverse transcriptase.

Translocation

—The movement of a gene or group of genes from one chromosome to another.