HIV and Malignancies

Cervical cancer and HIV are intersecting epidemics that both disproportionately affect low-income women. The impact of the socioeconomic disparity and biologic synergy of these two diseases is seen most dramatically in sub-Saharan Africa, where cervical cancer is the most common cancer killer among women, and new HIV infections are five times more likely to occur in young women than men. HIV-infected women are at increased risk for the development of cervical precancer and cancer, develop more aggressive lesions and are affected at younger ages.

In sub-Saharan Africa, the intersection between the HIV epidemic and the endemic nature of Kaposi's sarcoma-associated herpesvirus (KSHV) infection has resulted in Kaposi's sarcoma (KS) becoming the most common malignancy in many parts of the region. Now that highly active antiretroviral therapy (HAART) is becoming available in Africa, many patients with AIDS-related KS are receiving HAART alone as first-line therapy.

Neurologic complications of HIV infection are common. Among the most devastating of these is primary CNS lymphoma, an AIDS-defining illness which is highly aggressive and usually associated with short survival. Establishing the pathologic basis of focal brain lesions in the setting of HIV infection can be difficult for a number of reasons, including the fact that results of neuro-imaging and DNA PCR evaluations are non-specific and cytological testing of cerebrospinal fluid is highly insensitive.

The vast majority of HIV-infected individuals can now achieve and maintain undetectable viral load on antiretroviral therapy. However, HIV-infected individuals continue to be at higher risk for non-AIDS associated complications including malignancies which now account for the majority of deaths. Population-based epidemiologic studies have supported the finding that colorectal cancer (CRC) is significantly elevated in HIV-infected individuals compared to the general population.

Objective: Despite the availability of life-saving antiretroviral therapy (ART) in sub-Saharan Africa, our group and others have observed that a substantial proportion of individuals with Kaposi sarcoma (KS) initiate ART only after progressing to advanced-stage disease. While early-stage KS is likely to respond to ART alone, late-stage KS relies on chemotherapy and a sophisticated medical system capable of providing supportive care, neither of which are currently available in Uganda.

Among the most devastating neurologic complication of HIV is primary CNS lymphoma (PCNSL), an AIDS-defining illness usually associated with short survival. Establishing the diagnosis of AIDS-related PCNSL can be difficult for a number of reasons, including the fact that results of neuro-imaging including MRI and PET as well as EBV evaluations are non-specific and established cerebrospinal fluid (CSF) tests lack specificity and sensitivity. Moreover, standard interventions for AIDS-related PCNSL have not been improved upon in decades.

Kaposi's sarcoma (KS) is the most common type of cancer in HIV-1-infected individuals who are progressing to AIDS. In Uganda, KS accounts for four of every 10 cancer diagnoses made at the Uganda Cancer Institute and nine out of 10 of these patients are infected with HIV-1. Although highly active antiretroviral therapy (HAART) can promote KS-regression, nearly 50% of patients fail to achieve a total remission. Even with improved availability of antiretroviral therapy, KS remains a major clinical problem in sub-Saharan Africa.

Background:

Cancer remains an under-recognized health condition throughout most of Africa, and improved surveillance systems for determining cancer incidence, mortality, and prevalence of risk factors are badly needed. HIV and infectious diseases remain prevalent in Africa, with as many as 36 percent of cancers in Africa being infection-related — twice the world average.

The HIV epidemic has increased cervical cancer morbidity and mortality, especially in developing countries. The increased biologic risk for cervical cancer associated with HIV-infection combined with the strain on already overburdened health care systems work synergistically to increase the disparity in cervical cancer risk for women in these countries. Prevention efforts that have reduced the incidence of cervical cancer to close to zero in resource-rich countries are costly and not available in most low-resource settings.