Overview of Kaposi Sarcoma 

Kaposi Sarcoma (KS) is a cancer associated with Human Herpes virus 8 (HHV-8). It usually affects the mouth and skin, and more rarely, it can affect organs like the stomach and lungs. General symptoms include:

• Coloured spots on the skin (skin lesions)
• Weight loss
• Tiredness¹

There are more specific symptoms, especially when organs are affected :

• Cough when the lungs are involved 
• Diarrhoea and stomach pain if the stomach is involved 
• Swollen lymph nodes, if they are involved¹

KS was found in some people with human immunodeficiency virus (HIV)/Acquired immune deficiency syndrome (AIDS), but there were also many people with KS who did not have HIV/AIDS, leading scientists to suggest that there was something else involved in its development. HHV-8, which was first isolated in 1994 from KS lesions of HIV patients. Like other herpesviruses, HHV-8 is typically transmitted through saliva, and can also be transmitted sexually. The virus infects our cells, and can make them produce its own genes. This causes our cells to divide faster and live longer, avoiding apoptosis (programmed cell death).³

KS has been divided into four types, although non-typical cases also occur that may be more difficult to categorise:²

• Classic KS is usually found in elderly men of Mediterranean or Ashkenazi Jewish descent 
• Endemic KS is found in Equatorial Africa and is common in children. This type is aggressive and has a poor prognosis, and tends to involve lymph nodes 
• Epidemic KS is related to HIV/AIDS, and can occur even in well controlled HIV infections
• Iatrogenic KS is found in patients who have had organ transplants and are on immunosuppressant medication²

KS is more common when the immune system is weakened because this means it cannot fight off the HHV-8 infection.³ Some key risk factors for KS are HIV/AIDS and organ transplantation, which weaken the immune system, although there are other factors which will be mentioned here. It is important to understand the risk factors involved in KS so people can take steps to minimise their risk and seek medical help.

Risk factors

Immunosuppression

The first line of defence we have against viruses is our innate immune system, something we're born with. It reacts quickly when it identifies anything foreign that shouldn't be in our body, such as a virus, but it is a general response and usually slows down a viral infection rather than stopping it. This gives our adaptive immune response time to start working. The adaptive immune response specifically identifies and targets a virus in order to destroy it. It does so through T cells which can destroy infected cells, as well as by activating B cells, which secrete antibodies and macrophages, helping to rid you of viral infections.⁴

When the immune system is weakened, it can no longer fight off and prevent infections. In HHV-8 infection, the virus can be latent which is where it is present but does not cause symptoms. When the immune system is weakened, the virus can be reactivated and can multiply quickly, promoting the formation of tumours. This is when KS occurs.⁵ HHV-8 can also promote tumour formation through avoiding apoptosis as previously mentioned, as well as increasing inflammation and encouraging new blood vessels to grow. These new blood vessels will supply the tumour with oxygen and nutrients from our blood to help it grow.⁶

There are various common causes of immunosuppression, such as chemotherapy treatment for cancer, chronic illnesses, and immunosuppressant drug treatment following organ transplantation.

HIV/AIDS

HIV is a virus which can be transmitted through bodily fluids, including blood, amniotic fluid, and vaginal and anal fluid. This means it can be transmitted during sexual contact as well as during pregnancy and through the reuse of equipment such as needles. ⁷ Reports on the first confirmed case of HIV are conflicting, but it quickly became an epidemic after its discovery in the United States (US) in 1981.⁷ 

The virus specifically infects and then destroys CD4+ T cells, which are involved in our immune response, as discussed above. HIV first binds to the cells by specific receptors and inserts its genetic material into the cell. Its genetic material can then integrate into our cell's DNA, and it can produce more HIV proteins to build more of the virus. These will then be assembled into new HIV particles, which are pushed from the cell. This process can cause the cells to burst, destroying them so they can no longer play their part in the immune response.⁸ 

If untreated, HIV can progress to AIDS. This is where the immune system cannot fight off infections, leaving people susceptible to opportunistic infections, which can cause death. AIDS is said to occur when AIDS-defining conditions arise. These include KS, as well as:

• Invasive cervical cancer 
• Tuberculosis (TB)
• Cytomegalovirus retinitis 
• Candidiasis of the pulmonary/digestive tract 
• HIV encephalitis 
• Non-Hodgkin lymphoma⁷

While the rate for KS is relatively low in healthy individuals with HHV-8, it is much higher in people with AIDS, and this is known as epidemic KS. The risk is related to the number of CD4+ T cells a person has because the fewer they have, the weaker their immune system will typically be, allowing HHV-8 to replicate.⁹

Antiretroviral therapy (ART) involves using medication that prevents a virus from replicating. This prevents the death of CD4+ cells and therefore prevents further damage to your immune system. With treatment, over time, the virus will become undetectable in your blood. ART is one crucial way you can reduce your risk of developing KS, as it prevents the progression of HIV to AIDS and maintains your immune system, allowing it to repair itself.¹⁰

Organ transplantation

Organ transplantation is a treatment option for patients when their organs are failing, and it involves receiving an organ donated from someone else. However, when this is done, your immune system recognises that this is foreign, and not your own and therefore attacks it. To minimise the risk of this, you must be a match with the donor.¹¹ This is based on factors such as:

• Blood type
• Tissue type 
• Height and weight 

To prevent rejection, after a transplant, you will need immunosuppression medication, which will reduce the immune response. Unfortunately, there are side effects to these medications, including an increased risk of infection and skin cancer.¹¹

People on immunosuppressants are at an increased risk of cancer caused by viruses, including KS. Typically, HHV-8 predates the transplant, and once immunosuppression starts, the virus can be reactivated, allowing it to multiply quickly, potentially leading to KS. This is called Iatrogenic KS.¹²

It is important to monitor transplant patients and conduct screening to identify cases early, in order to direct treatment plans. One way to manage Iatrogenic KS is to lower the dose of immunosuppressant medication and allow the immune system to repair itself and fight off the infection. Chemotherapy can be used, particularly in widespread cases of KS, which can shrink lesions and improve symptoms.¹² 

Other contributing factors

HHV-8 is more prevalent in certain areas, such as the Mediterranean, where classic KS is common, as well as areas where it is endemic, such as sub-Saharan Africa, which is known as endemic KS. In areas where HHV-8 is endemic, there is a higher incidence of KS because it is the causative agent. There is some overlap here with epidemic KS, because sub-Saharan Africa has high rates of HIV due to poverty and limited access to healthcare.¹³

KS is also more prevalent in those assigned male at birth (AMAB) than those assigned female at birth (AFAB), particularly in those who are AMAB who have sex with others who are AMAB (MSM), due to increased rates of HIV. This increased rate is because anal sex has a higher risk of HIV transmission than other intimate acts. Studies have found that those who are AMAB are also more likely to be infected with HHV-8 than those who are AFAB in Sub-Saharan Africa, even when excluding MSM, however, this was not found in other regions. This suggests that those who are AMAB may be more susceptible to HHV-8 infection than those who are AFAB, either due to behavioural or biological factors. One example suggested is that due to sex hormones, those who are AFAB have a stronger immune response, which might allow them to prevent infection and reactivation of the virus better than those AMAB. This would not explain why in other regions, infection rates are more similar, therefore, more research is needed.¹⁴

Conclusion

The main risk factors for KS are HIV/AIDS and organ transplant immunosuppression therapy, however, there are other risk factors which are less understood, including gender and geographical location. Understanding these risk factors is important in order to minimise risk.

Regular screening in at-risk groups allows for early detection and better healthcare. This includes screening HIV and organ transplant patients for HHV-8, and monitoring them for any symptoms of KS. The best way to minimise risk in these groups includes ART for HIV patients to maintain their immune system and prevent the development of AIDS and KS, and adjusting immunosuppressant medication in transplant patients in order to lower doses and allow the immune system to fight off infection.