Wednesday, March 29, 2023

Part I

We have previously commented on the fact that the immune system has multiple roles and impacts with regard to cancer. A major one, of course, is the prevention of cancer in the first place. So how exactly does that play out? There are several ways in which dysfunction in the immune system can increase the risk of cancers of one type or another. In future articles we will discuss some of the other ways, but today we address infection with HIV (human immunodeficiency virus) and its resultant manifestation as acquired immunodeficiency syndrome (AIDS).

Those of us who have been around for a while will recall the onset of the epidemic of AIDS from around 1981. AIDS itself is not a neoplastic disease or cancer. It is a disease of T cells, one of the types of immune cells that protect against various pathogens. Thus, a weakening of the T cells of the body leads to susceptibility to the pathogens from which those particular lymphocytes usually provide protection. In the context of AIDS, these particular pathogens and infections were diseases which were only rarely seen previously—pneumocystis pneumonia, various fungal infections such as esophageal candidiasis—and tuberculosis as well. Aside from these opportunistic infections, AIDS also induced certain constitutional problems, such as weakness, cachexia, weight loss and lymphadenopathy.

For our purposes, AIDS also predisposed to a spectrum of malignancies that became classical—Kaposi’s sarcoma, Burkitt lymphoma, primary central nervous system lymphoma, anal cancer and cervical cancer. What these malignancies share in common is that they are each caused by viruses. Thus, while in healthy individuals the immune system and its T cells are able to provide immunological resistance to these predators, the individual with AIDS has a weakened defense, which makes him/her more susceptible to KSHV8 (Kaposi’s sarcoma herpesvirus 8) or Epstein-Barr virus or human papillomavirus as well as other pathogens. Interestingly, patients who have undergone organ transplants (liver, lung, heart, kidney) and are on medications for immunosuppressive therapy to prevent rejection of the transplanted organ are at elevated risk for precisely the same spectrum of malignancies.

Two things have turned the tide in the U.S. with regard to HIV. One was the success of educational programs, which promoted safe sexual practices—the use of condoms and the like so as to reduce sexual transmission of the disease. Likewise, safer needle practices for addicts have also played an important role in prevention from that point of view as well.

Perhaps more important has been the development of antiretroviral therapy (the HIV virus is a retrovirus) which is highly effective in controlling the disease in carriers. This has had a dual function. It has turned HIV carrier status into a chronic disease for those who are infected. In addition, those at high risk, such as gay or bisexual individuals or prostitutes, can take these drugs prophylactically and thus reduce the risk of infection.

While a vaccine for HIV would be a marvelous development, it has apparently been elusive for vaccine researchers to create—I am not savvy on the science for this. In the face of the recent resistance to the vaccines for COVID, I have to wonder how it would be received, but certainly it would be a fantastic step forward.

It is estimated that there are now something over 1 million people living with HIV in the U.S. Survival after an HIV infection is estimated to be around 10 years, while survival after the development of AIDS (the development of one of the opportunistic infections or cancers) if left untreated is in the range of one year. However, with the widely available antiretroviral therapy, life expectancy now for someone living with HIV can almost reach that of a healthy uninfected individual.

It is believed that HIV originated in an animal reservoir, probably in a primate, somewhere in Africa and made the jump to humans for some reason in the early to mid-1950s. Thus, there may have been some cases in Africa prior to its recognition in the U.S., but this origination in Africa may, in part, be responsible for its subsequent explosive widespread epidemic spread throughout the African continent, where it has wrought untold devastation.

In our next episode of Thoughts on Cancer we will discuss the epidemic of AIDS in sub-Saharan Africa and the changes that are now coming about with the availability of antiretroviral therapy, leading to profound changes in its future.

Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York.

This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.

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