 |
 |
|
|
Patrick S. Moore, MD, MPH |
|
|
 |
|
|
Yuan Chang, MD |
|
|
 |
|
|
A. Scott Laney, MPH |
|
Patrick S. Moore, MD, MPH
Professor Molecular Genetics and Biochemistry
Program Leader, Molecular Virology Program
Yuan Chang, MD
Professor of Pathology
Basic Research Division
A. Scott Laney, MPH
Department of Epidemiology
Graduate School of Public Health, University of Pittsburgh
Most people know herpes (or, more formally, herpesviruses) as the cause of cold sores on the lips or sexually-transmitted herpes--essentially cold sores on the genitals. Herpesviruses actually include eight very different viruses that cause diseases such as chickenpox, shingles, mononucleosis and even cancers. The most recently discovered herpesvirus, KSHV (also called HHV-8) causes the most common form of cancer in AIDS patients.
KSHV and Cancer
Kaposi's sarcoma-associated herpesvirus (KSHV) was named after the disease Kaposi's sarcoma (KS) in which it was first isolated. KS is a cancer of the cells lining the channels of the lymphatic system and usually appears as a lesion on the skin of the face, hands, and feet. The lymphatic system is composed of a network of lymph nodes and channels that carry lymph fluid, nutrients, and waste material between the bloodstream and tissues. It is a critical component of the immune system. KS tumor cells form abnormal channels filled with blood cells, which give KS tumors a bluish, bruised appearance. It can invade the lungs or intestines, which is particularly serious because of the risk of internal bleeding.
KS was first described by Moritz Kaposi in 1872 as an uncommon tumor of elderly men, especially those of Mediterranean descent. In the early 1980s, KS became epidemic with the onset of AIDS, with up to half of AIDS patients developing this cancer, particularly gay and bisexual men. This led to the idea that KS might be caused by a second, sexually-transmitted virus besides HIV.
In 1994, our laboratory found KSHV in KS tumors, which we subsequently analyzed and for which we developed blood tests. It has since been found to also cause two abnormalities of the B cells (a cancer known as primary effusion lymphoma and multicentric Castlemen's disease), which are part of the immune system and make antibodies to fight infections.
The estimated annual incidence rate for KS is 5 cases per 100,000/year in the US. In parts of Africa, where the virus is common, KS is the most frequently reported cancer and remains a major unaddressed public health issue.
Two factors are required for individuals to develop KS: First, they must be infected with KSHV. Infection rates for KSHV vary among different populations and, therefore, so do the risks for developing KS (Table 1). KSHV is uncommon in the general population of the US and northern Europe (less than 3%), with higher infection rates seen in Mediterranean and Middle Eastern countries (5%--20%). The highest rates are found in subSaharan Africa and in some Amazonian populations (more than 50%). Some groups, such as gay men and persons from specific ethnic backgrounds, have higher than average rates of infection. Second, they must have immunosuppression either globally--as in the case of AIDS--or due to localized immunity loss, such as that associated with aging. The risk of KS in young adults who are otherwise healthy is exceptionally low. Men are at higher risk for KS than women, but KS can occur in women (Table 2).
Table 1. Rates of Kaposi's Sarcoma-Associated Herpesvirus Infection Worldwide.
| Northern Europe, Asia, and US |
0-5% |
| Mediterranean populations |
2%--25% |
| African populations |
more than 50% |
Table 2. Risk Factors for Kaposi's Sarcoma
| Immunosuppression |
| Older than age 65 |
| Male homosexual activity; multiple sex partners |
| High-risk ethnic background (subSaharan African, Mediterranean, Ashkenazi, Middle Eastern) |
| Male |
How is KSHV Transmitted?
KSHV, like genital herpes, is primarily a sexually-transmitted virus in the US, although nonsexual transmission can occur. Among gay and bisexual men, infection rates reach 40%--50%, but it remains unknown right now what specific sexual practices lead to infection or why gay men are at higher risk. The virus usually is not present in semen or vaginal fluids; it is shed into saliva, suggesting that either deep kissing or use of saliva as a lubricant during sex may contribute to its spread. Increase in safe sex practices has decreased KSHV--as well as HIV--transmission.
Heterosexual activity probably transmits KSHV but at a much less efficient rate. It is extremely rare for heterosexual partners of KS patients to also develop this tumor. Nonsexual transmission accounts for most of the infection among persons of Southern European, Middle Eastern, and African descent. How this occurs remains a mystery. We do know that children in the US are almost never infected and transplacental mother-to-child transmission is rare.
Organ transplantation transmission of KSHV is a major concern for physicians. Transplant recipients who become infected from a donor organ, or who were already infected prior to transplantation, have a 25% chance of developing KS. The risk is highest in the first year after transplantation and decreases as immunosuppression is reduced. KSHV may be transmitted through blood transfusions, but this is rare. Although KSHV blood tests exist as research tools, they are not generally available for clinical use. Neither the blood nor organ supplies are currently tested for infection.
Consequences of Infection
Most KSHV infections are asymptomatic and more than 95% of persons who become infected never develop KS or other KSHV-related cancers. Once exposed to KSHV, infection is lifelong but the immune system of healthy adults keeps the virus in check. For this reason, persons who receive an organ transplant, chemotherapy, or who have AIDS are at risk for KS if they are KSHV infected. In addition, aging affects the immune system and elderly persons who may have acquired infection as youths can sometimes develop this tumor. Regardless of how a person becomes infected with KSHV, the resulting infection is likely to be benign as long as a healthy immune system is maintained.
Even in persons with AIDS, KS can be relatively mild. Some KS patients live with this tumor for decades. But if the patient's immune system is severely compromised, KS may disseminate and become life-threatening.
Treatment and Prevention
If KS tumors are localized, surgical removal or local chemotherapy may be effective. This has no effect on the underlying viral infection but often controls the tumor. There is no vaccine for KSHV and existing therapies target tumor cells rather than the underlying viral infection. Drugs to treat other herpesvirus infections, such as ganciclovir, do show promise in preventing KS. Effective treatment against HIV usually improves or eliminates KS in AIDS patients, but scientists are concerned that there may be a resurgence of KS among these patients as they grow older.
Prevention depends on avoiding infection and maintaining a healthy immune system. Though it is not always possible to prevent viral infection, the risk of infection can be dramatically reduced through safe sex practices. For immunocompromised persons who are at high risk, awareness of an expanding "bruise" that does not heal or of internal bleeding can lead to earlier diagnosis and treatment.
