What is Herpes Virus Type 8?
Viruses cause up to 20% of all cancers in humans. Two such viruses, Human Herpesvirus-8 (HHV-8), also known as Kaposi sarcoma Herpesvirus (KSHV), and Epstein-Barr virus (EBV or HHV4), are members of the Herpes family of viruses. These are the only two Herpes viruses known to cause cancer in humans. For instance, EBV causes a type of cancer known as Burkitt lymphoma. Other cancer-causing viruses include Human Papillomavirus (HPV), Hepatitis B (HBV), and Human T-cell lymphotropic virus-1 (HTLV-1). In 1994, it was discovered that HHV-8 causes a skin cancer known as Kaposi sarcoma (KS). Since then, many studies have found that this virus is found more commonly in certain parts of the world, but no one can explain why this is the case.
What Causes Herpes Virus Type 8?
The HHV-8 or KSHV is a type of virus that falls under the category of gammaherpesviruses. These viruses can infect the lymph system, skin, blood vessels, and organs, and sometimes remain dormant in their host cells for a lifetime. The HHV-8 virus can stay inactive in the body’s B-cells and in the cells lining blood vessels. Under certain conditions such as weakened immunity, malnutrition, or organ transplantation, this virus can activate and start to multiply.
When active, the HHV-8 virus can cause a form of cancer called Kaposi sarcoma, as well as certain diseases related to the body’s B-cells, such as primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). People who have HIV are at a significantly higher risk of developing these cancers; however, they can also develop in people who don’t have HIV.
Kaposi sarcoma is a cancer that impacts the lymph and blood vessels, which was first discovered in 1872. It is mainly associated with AIDS, and it can create pigmented lesions on the skin. There are four forms of this disease, depending on how it presents and the context of the individual.
Classic or sporadic Kaposi sarcoma usually appears in older Jewish and Mediterranean, Eastern European HIV-negative men, and it’s typically less aggressive. Iatrogenic Kaposi sarcoma can develop after an organ transplant, presenting with swollen glands and organ involvement. Epidemic or AIDS-associated Kaposi sarcoma is the most aggressive form. Lastly, endemic Kaposi sarcoma occurs in Africa and can be highly aggressive in adults and children.
Primary effusion lymphomas (PELs) are rare and usually associated with AIDS. They occur in the fluid-filled spaces of the body, such as the space around the lungs, heart, or in the abdominal cavity. However, the disease does not usually create a solid tumor, and it’s considered a type of non-Hodgkin lymphoma.
Multicentric Castleman Disease (MCD) is another rare condition that impacts the lymph system. It shows up in both people with and without HIV/AIDS, and it can cause symptoms like fever, chills, and swollen glands. MCD may at first appear like a bacterial infection and requires a high level of suspicion for accurate diagnosis. If not treated quickly, MCD could develop into a sepsis-like syndrome and potentially evolve into a large B-cell lymphoma.
Risk Factors and Frequency for Herpes Virus Type 8
HHV-8/KSHV, also known as the Kaposi’s sarcoma-associated herpesvirus, comes in seven different forms: A, B, C, D, E, F, and Z. It’s found in about 5% to 20% of the population worldwide. However, it’s more frequently seen in sub-Saharan Africa, possibly due to its transmission through saliva, which is common in both adults and children in this region. Another reason for the high prevalence in this region could be the widespread occurrence of malaria. In contrast, the United States has the lowest prevalence, with less than 10% of the population affected.
On a global level, the virus is two to three times more common in men than in women, and particularly more frequent in men who have sex with men when compared to heterosexual men. This is especially true in regions where the virus is not prevalent. Among all sexual categories, women have the least prevalence of the virus. However, it should be noted that it’s not definitively established as a sexually transmitted infection.
The chance of getting this virus through blood products and from mother to child at birth is quite small. It can spread through body fluids, with saliva being the most common medium. Most of these infections don’t show symptoms and may go unnoticed.
Signs and Symptoms of Herpes Virus Type 8
Kaposi sarcoma is a disease that can manifest in various ways, depending on which parts of the body it impacts. The most common sign is skin lesions, but it can also affect many different organs and systems inside the body.
The symptoms of Kaposi sarcoma are:
- Skin related: The primary signs are lesions which can be red, brown, or purple. These lesions could be in the form of a patch, plaque, or nodule. Sometimes they can be ulcerated, which may be painful and have a risk of leading to cellulitis. These lesions could also cause vascular blockage. Swelling around the face and eyes is common if the lesions are near these areas. In extreme cases, vision loss can occur.
- Gastrointestinal impact: When the disease impacts the gastrointestinal system, it could lead to a variety of symptoms. Some individuals may not experience any symptoms, while others might have abdominal discomfort, blood in stools, weight loss, constipation, or even intestinal obstruction.
- Pulmonary effects: If the lungs are affected, symptoms could include coughing, breathing difficulty, and coughing up blood.
Testing for Herpes Virus Type 8
Diagnosing diseases related to the Human Herpesvirus 8 (HHV-8), such as Kaposi’s Sarcoma (KS) and Multicentric Castleman’s disease (MCD), mainly involves looking at the patient’s symptoms and taking a tissue biopsy. A biopsy involves removing a small piece of tissue from the skin lesion in KS and from the lymph node in MCD to examine it under a microscope.
In addition to the biopsy, a technique known as immunofluorescence staining is often used. This technique uses a special marker called KSHV – LANA, which is highly specific for KS, to help identify the disease.
Additional tests include a complete blood count, which measures the number of different types of cells in your blood, and serum chemistry, which looks at the different chemicals and substances in your blood. Testing for HIV is also necessary given its association with HHV-8 related malignancies.
Relevant imaging tests, akin to X-rays or scans, may also be performed to get a complete picture of the patient’s health and to confirm the diagnosis.
Treatment Options for Herpes Virus Type 8
Starting antiretroviral therapy early in AIDS-associated Kaposi Sarcoma (KS) can possibly cause the disease to regress. The choice of treatment for KS depends on how far the disease has advanced, the patient’s immune status, and how widely the disease has spread. For small lesions, localized chemotherapy with a drug called vinblastine, surgery or radiation therapy could be options. The World Health Organization recommends antiretroviral therapy for mild or moderate Kaposi sarcoma. If the disease is severe, a combination of antiretroviral therapy and systemic chemotherapy is recommended. Commonly used drugs for severe cases include paclitaxel and pegylated liposomal doxorubicin. For diseases associated with the HHV-8 virus, which can lead to formation of Kaposi sarcoma, different combinations of antiviral drugs have been shown to be effective.
For primary effusion lymphoma (PEL), a combination chemotherapy-based treatment is typically used, which can include drugs like cyclophosphamide, doxorubicin, vincristine, and prednisone. In patients with HIV/AIDS, this approach, combined with antiretroviral therapy, has an average survival rate of about 40%. In patients without AIDS, liposomal anthracycline may be used, sometimes in combination with other drugs such as bortezomib and prednisone. If a patient is unable to tolerate chemotherapy or has a type of PEL that is resistant to chemotherapy, radiation therapy is another possible treatment.
In multicentric Castleman disease (MCD), a combination chemotherapy is often indicated, especially when there are systemic symptoms. Other treatment options include surgical removal, radiation therapy, and different immunological agents like steroids and rituximab (an anti-CD20 agent). Rituximab can be used alone or in combination with other therapy.
There are several different drugs in different stages of testing that target various stages of the development of diseases associated with the HHV-8 virus. Some of these include drugs that inhibit a protein called NF-κB, which is involved in different stages of the cancer-causing process. Other drugs being tested target molecules like interleukin-2, interleukin-6, mTOR, MAPK/RTK signaling pathways, and the growth of new blood vessels.
What else can Herpes Virus Type 8 be?
- Chancroid: a sexually transmitted infection
- Candidiasis: a fungal infection usually caused by a yeast called candida
- Herpes zoster: a viral infection that causes a painful rash and is also known as shingles
- HIV lymphadenitis: a condition marked by swollen lymph nodes often seen in people with HIV
- Hand foot and mouth disease: a contagious illness usually affecting children that causes sores in the mouth and rashes on the hands and feet
- Kaposi Sarcoma: a type of cancer that forms in the lining of blood and lymph vessels, typically in people with weakened immune systems
- Kaposi Sarcoma Inflammatory Cytokine Syndrome (KICS): a condition associated with Kaposi’s Sarcoma, characterized by severe symptoms due to high levels of inflammatory substances in the body
- Syphilis: a sexually transmitted bacterial infection
