What Are HIV and AIDS? Does AIDS Cause Cancer?

What is HIV?

HIV stands for Human Immunodeficiency Virus (the human immunodeficiency virus), and by damaging the immune system, it can lead to various diseases and, in the longer term, the syndrome called AIDS . This virus suppresses our immune system and can create conditions for other viruses, such as EBV and HPV , to remain in the body and cause disease and cancer.

Viruses and bacteria can cause cancer. Indeed, 16% of all cancers are thought to result from long-term infections caused by microorganisms and the body's immune response to them. The role of microorganisms in cancer development is being investigated through metagenomic studies.

How Does HIV Disrupt the Immune System?

When we examine the role of HIV in the immune system, CD4-positive T cells come to the fore. HIV settles in CD4 + T cells and destroys them, severely damaging the immune system. As a result of this immune suppression, individuals may present with a wide variety of conditions: a severe course of a simple infection, enlarged lymph nodes, recurrent cold sores, weight loss, unexplained fever, opportunistic infections (tuberculosis, thrush, certain bacteria and fungi), and even some cancer types [Kaposi sarcoma, cervical cancer, certain lymphomas, etc.].

What is AIDS?

AIDS is the abbreviated name of the disease caused by HIV. Acquired Immuno-Deficiency Syndrome (Acquired Immunodeficiency Syndrome) is an infectious disease seen in people infected with HIV (HIV-positive), characterized by suppression of the immune system.

AIDS may not appear in HIV-positive individuals for many years, and may emerge in later years as the final stage of HIV infection.

For HIV diagnosis, the ELISA test performed at least 3 months after a risky exposure provides the most accurate result.

The increase in pneumonia and Kaposi sarcoma among homosexual men in New York and California after 2015 is considered an early warning of the AIDS epidemic (outbreak) and draws the medical world's attention in this direction.

Which Cancers Are Associated with HIV?

In the United States, before anti-HIV (antiretroviral) treatment began in the mid-1990s, certain cancers in HIV+ individuals, such as Kaposi sarcoma, aggressive b-cell lymphoma and cervical cancer, were 30% more common than in the general population. After anti-HIV treatment, this frequency was seen to fall by 70%; after the 2000s, the decline continued, although more moderately. However, these diseases remain markedly more common in HIV-positive people than in the general population.

Meanwhile, because antiretroviral treatment improves survival in HIV-positive individuals, the number of people with AIDS in the United States has increased more than 2-fold, and this group's average age has also increased. Since a large proportion of HIV-positive individuals or people with AIDS are now at ages when cancer becomes more common, other cancers unrelated to HIV are also seen more frequently. Thus, the burden of HIV-related cancers in HIV-positive individuals has remained relatively stable over the last 20 years, while the burden of cancers unrelated to HIV is increasing.

Because smoking is common among HIV + individuals, lung cancer incidence is higher in HIV + individuals. Being HIV-positive also adversely affects treatment outcomes.

What is Kaposi Sarcoma, and How is it Related to HIV?

Kaposi sarcoma is a type of soft tissue sarcoma. It generally develops beneath the skin's surface or in tissue lining the mouth, nose or anus.

The fact that Kaposi sarcoma is more common among homosexual men than in other groups at risk of HIV infection suggested that a second infectious agent might play a role in its etiology (causes). In 1994, Chang and colleagues discovered a new herpesvirus called HHV8 in people with Kaposi sarcoma, confirming this claim. Following this finding, research based on the idea that other viruses could cause the other cancers seen more often in HIV + individuals led to the identification of other oncoviruses such as EBV, HPV, HBV and HCV.

Kaposi sarcoma is a multicentric tumor ranging from a few oral mucosal (inside the mouth) lesions to multiple lesions involving one or more organs, particularly the oral mucosa, digestive system, lymph nodes, lungs and bones. Its subtypes are the classic, endemic, transplant-related and epidemic (AIDS)-related forms. HHV8 causes all of these forms.

HHV8 encodes a series of genes that trigger cell proliferation, cytokine production and new blood vessel formation , thereby causing cancer development. Kaposi sarcoma lesions generally develop in the legs because HHV8-encoded genes activated by factors triggered in this relatively oxygen-poor region, compared with other body regions, facilitate tumor development.

In HIV-related Kaposi sarcoma, anti-HIV (antiretroviral) treatment must be combined with local therapies such as radiotherapy and treatments such as 9cis-retinoic acid. Although the response to antiretroviral treatment is very good, surgery generally takes a secondary role. In individuals who do not respond to antiretroviral treatment, systemic treatment is considered the best option.

What Other Diseases Are Associated with HHV8?

• Primary Effusion Lymphoma (80% coinfection with EBV)
• Multicentric Castleman Disease
• HHV8 Inflammatory Cytokine Syndrome

Which Lymphomas (Lymph Cancers) Are Associated with HIV?

After the HIV-lymphoma association was established, lymphomas received a new classification and new lymphoma types were identified. In many HIV-related lymphomas, particularly primary central nervous system lymphoma, Hodgkin lymphoma and plasmablastic lymphoma, tumor cells infected with EBV (Epstein-Barr virus) are observed; however, some other lymphomas, such as Burkitt and diffuse large b-cell lymphoma, are known to be EBV-negative.

Plasmablastic lymphoma is an EBV-associated aggressive tumor identified in the jaws of patients with HIV. In Hodgkin lymphoma, Reedstenberg cells are generally associated with EBV. Clinically, HIV + individuals with Hodgkin lymphoma are more likely to present at older ages, with B symptoms (such as fever, night sweats and weight loss) and abnormal presentation (unexpected disease findings).

Since lymphoma can be the presenting sign of HIV infection, individuals with lymphoma should be examined thoroughly for HIV. Staging in individuals with aggressive HIV-associated lymphoma should include central nervous system involvement. Central nervous system involvement can be assessed using methods such as gadolinium-enhanced (contrast) MRI, PET scanningand biopsy.

In HIV-related lymphomas, overall survival was below 20% before antiretroviral therapy (ART), whereas it is now seen to exceed 80% after treatment regimens including ART.

Other HIV-Associated Lymphatic System Diseases

• Diffuse Large B-Cell Lymphoma
• Burkitt Lymphoma
• Primary Effusion Lymphoma
• HHV-associated multicentric disease
• Castleman disease
• Hodgkin Lymphoma

HPV (human papillomavirus)-Associated Cancers

HPV-associated cancers include particularly cervical cancer and anal cancer , as well as 30% of head and neck cancers and the great majority of intraoral cancers. These clinical conditions occur when HPV infection is added to the picture as a result of immune suppression in HIV+ individuals. Identifying and managing precancerous lesions plays a very important role in this process. Therefore, cervical cancer screening is particularly important in HIV + women. Although anal cancer is seen more often in homosexual men, similar screening programs have also been developed for anal cancer.

Can HIV-Associated Cancers Be Prevented?

Most HIV-associated cancers are caused by oncogenic viruses or other exogenous agents and are potentially preventable. The most important approach is early diagnosis and treatment of HIV. In addition, HPV-associated cancers can be prevented by vaccination. HPV vaccines are most effective when administered to both girls and boys before age 26. In addition, HBV (hepatitis-B) vaccination can reduce liver cancer risk, while preventing HHV8 transmission can reduce the risk of Kaposi sarcoma. Considering transmission through body fluids, patient education and public health measures focusing on reducing transmission have been proposed as potentially effective, although this has not been definitively demonstrated in controlled studies.

Smoking cessation is particularly important in this process. Smoking is more common among many HIV + individuals than in the general population, and lung cancer is one of the leading causes of cancer-related death. Patients aged 55-80 with a 30-pack-year smoking history should undergo annual lung cancer screening with low-dose computed tomography.

Conclusion

Although advances in antiretroviral therapies have brought major progress in improving overall survival and reducing the frequency of HIV-associated cancers, cancers unrelated to HIV remain the main cause of complications and death.

Among more than 35 million HIV+ people worldwide, new research into screening for causative agents and cancer prevention, diagnosis and treatment is producing new approaches, and hopes for managing disease in HIV+ individuals continue to grow.