Factors contributing to risk for cancer among HIV-infected individuals, and evidence that earlier combination antiretroviral therapy will alter this risk

Abstract

Purpose of review To critically appraise recent published literature about factors associated with cancer risk likely to be influenced by combination antiretroviral therapy (cART) in HIV-infected individuals, and the potential of earlier cART initiation to reduce this risk. Recent findings Factors leading to increased risk of non-AIDS defining malignancies (NADM) in particular remain poorly understood. Immunodeficiency appears to be key, whereas evidence is emerging that a direct pro-oncogenic effect of HIV, activated inflammatory and coagulation pathways, and cART toxicity may also contribute. By reducing HIV replication, improving immune function and limiting chronic inflammation, cART initiation at higher CD4+ cell counts may therefore reduce NADM risk. However, cART only partly normalizes enhanced inflammation and coagulation seen during HIV infection and conflicting laboratory and epidemiological data have been reported as to if (and how) cART affects NADM risk. Furthermore, secondary analyses of randomized controlled trials comparing early versus delayed cART initiation were inconclusive. Summary Continuous epidemiological surveillance is warranted to monitor trends in cancer incidence among HIV-infected individuals and to better understand the impact of earlier cART on NADM risk. The role of adjuvant anti-inflammatory or anti-thrombotic therapies to reduce cancer risk deserves further investigation.

Human Papillomavirus in the HIV-Infected Host: Epidemiology and Pathogenesis in the Antiretroviral Era

“…This effect, if present, would likely consist of mechanisms independent of ART and may involve ongoing attenuation of cell-mediated immunity or to the presence of persistent inflammation [97].…”

Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection

“…With the changing epidemiology of cancer during HIV infection, the traditional classification into AIDS-defining and non-AIDS-defining cancer, implemented in the early 1990s for surveillance purposes [23], became outdated [18]. The classification of cancer into infection-related and infection-unrelated seems to us to be more appropriate because it considers a wider range of cancer types whose incidence is increased during immunosuppression and establishes a framework to better understand the interplay between viral coinfections, HIV, and carcinogenesis.…”

“…HIV-infected persons also have an increased risk of infection-unrelated cancer [17]. Reduced control of oncogenic viruses and impaired immune surveillance of malignant cells may facilitate carcinogenesis during HIV infection [18].…”

Cancer Knowledge and Opportunities for Education Among HIV-Infected Patients in an Urban Academic Medical Center

“…It is unclear why HIV-infected patients have more advanced stage cancer at presentation, although immunosuppression, altered tumor biology, and delays in presentation to care have been suggested [8][9][10]. Additionally, HIV disproportionately affects people of lower socioeconomic status; thus, there may be additional factors that contribute to late stage cancer at diagnosis, including a lack of knowledge or awareness of cancer symptoms due to poor education and personal or structural barriers to accessing medical care.…”