The human immunodeficiency virus (HIV) targets the immune system, leading to acquired immunodeficiency syndrome (AIDS) if left untreated. Having AIDS, or living with chronic HIV infection, significantly increases the risk of developing several types of cancer compared to the general population. The underlying mechanisms involve the destruction of immune cells, persistent inflammation, and the inability to control cancer-causing viruses. This link has implications for the long-term health and management of individuals living with HIV.
How HIV Compromises Immune Surveillance
The primary target of HIV is the CD4+ T-cell, a type of white blood cell coordinating the immune response. As the virus replicates, it progressively destroys these cells, leading to profound immunodeficiency. This depletion of CD4+ T-cells impairs the body’s ability to execute immune surveillance—the process of recognizing and destroying abnormal or pre-cancerous cells before they develop into tumors.
The persistent presence of HIV, even when suppressed by medication, causes chronic immune activation and inflammation throughout the body. This continuous inflammatory environment introduces cellular stress and oxidative damage. This can promote genetic mutations and cellular proliferation, encouraging cancer development by fostering a microenvironment conducive to malignant cell growth.
A weakened immune system also struggles to keep common, cancer-causing viruses in check. These oncogenic viruses, often latent or harmless in a healthy person, can activate and drive tumor formation when immune control is lost. The environment created by HIV, marked by a lack of immune policing and a pro-inflammatory state, sets the stage for several virus-driven cancers to emerge and progress aggressively.
The Three AIDS-Defining Cancers
The connection between HIV and cancer is illustrated by the three cancers whose presence in an HIV-positive person defines the progression to AIDS. These malignancies, known as AIDS-defining cancers (ADCs), include Kaposi Sarcoma (KS), aggressive forms of Non-Hodgkin Lymphoma (NHL), and Invasive Cervical Cancer (ICC). The incidence of these three cancers is significantly higher in people with untreated HIV compared to the general population.
Kaposi Sarcoma develops from the cells lining lymph or blood vessels and is linked to the Human Herpesvirus 8 (HHV-8). In individuals with a healthy immune system, HHV-8 infection is usually asymptomatic. However, HIV-induced immunosuppression allows the virus to reactivate, driving the formation of characteristic purplish skin lesions and internal tumors. The risk of KS is hundreds of times higher in people with AIDS than in those without.
Certain types of Non-Hodgkin Lymphoma (NHL), specifically high-grade B-cell lymphomas such as diffuse large B-cell lymphoma and Burkitt’s lymphoma, are AIDS-defining. These lymphomas arise when the weakened immune system fails to control B-cell proliferation, often stimulated by co-infecting viruses like the Epstein-Barr Virus (EBV). These lymphomas are aggressive and can affect the central nervous system, making them a serious complication of advanced HIV disease.
Invasive Cervical Cancer (ICC) is the third ADC, nearly always caused by persistent infection with high-risk strains of the Human Papillomavirus (HPV). While HPV is common, the compromised immunity of HIV-positive women allows the virus to persist and progress from pre-cancerous lesions to invasive cancer more rapidly. Due to this high risk, screening for cervical cancer is recommended throughout the lifetime of women living with HIV.
Cancers with Increased Risk in HIV-Positive Individuals
Beyond the ADCs, Non-AIDS Defining Cancers (NADCs) also occur at an elevated rate in people living with HIV. These cancers are common in the general population but appear earlier and are often more aggressive in HIV-positive individuals, even with effective Antiretroviral Therapy (ART). NADCs represent a growing fraction of the cancer burden as life expectancy for people with HIV increases.
Anal cancer risk is substantially elevated, up to 25 times higher in this population, and is caused by persistent infection with high-risk HPV strains. Similar to cervical cancer, the immune system’s inability to clear HPV leads to a high prevalence of pre-cancerous anal lesions that can progress to malignancy. This heightened risk is a focus of current screening efforts.
Lung cancer is one of the most frequent NADCs, with a risk three to four times greater than in the general population. While smoking is a major shared risk factor, HIV infection and chronic inflammation appear to exacerbate the risk, suggesting HIV contributes to lung cancer development independent of tobacco use. Liver cancer is also more common, largely because co-infection with Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) is frequent. The combination of HIV-related immune dysfunction and chronic viral hepatitis accelerates the liver damage and inflammation that drive tumor formation.
Prevention and Early Detection Strategies
The most effective measure for reducing cancer risk in people with HIV is the consistent use of Antiretroviral Therapy (ART). ART suppresses the HIV viral load, allowing the CD4+ T-cell count to rebound and restoring immune function. Restoring immune surveillance dramatically lowers the incidence of ADCs, such as Kaposi Sarcoma and Non-Hodgkin Lymphoma.
Long-term viral suppression through ART also reduces the risk of certain NADCs, including anal and liver cancers, by improving overall immune health and reducing chronic inflammation. However, ART alone does not eliminate the risk, making prevention and early detection through screening essential. Lifestyle changes, such as smoking cessation, are recommended to lower the risk of lung and other tobacco-related cancers.
Regular, targeted screening is a cornerstone of cancer prevention for people with HIV. Due to the high risk of HPV-related malignancies, guidelines recommend frequent cervical cancer screening via Pap tests throughout a woman’s lifetime. Annual anal Pap smears are often recommended for high-risk individuals to detect pre-cancerous lesions early, as treating these lesions reduces the risk of anal cancer.