AIDS and 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 IDS-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 singlestranded 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 cavitybased
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 HIVpositive
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, and
melanoma (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 can-
cer 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 AIDSrelated
infection, such as thrush or Pneumocystis carinii
pneumonia (PCP).
Another special concern for patients with AIDSrelated
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 slowgrowing
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.
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