Large study finds advanced stage cancer more common in HIV-positive people

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  • U.S. study finds people with HIV more likely to be diagnosed with advanced cancer
  • Researchers suggest HIV is likely also responsible for reduced chances of survival
  • The findings reveal the importance of regular cancer screening for people with HIV

HIV infection increases the risk of the following cancers:

  • non-Hodgkin’s lymphoma – caused by Epstein-Barr virus
  • Kaposi’s sarcoma (KS) – caused by human herpes virus-8
  • invasive cervical cancer – caused by strains of human papilloma virus (HPV)

All of the viruses mentioned above that incite the development of abnormal cells that in some cases ultimately transform into pre-cancer and cancer are spread in similar ways as HIV.

The widespread availability and use of HIV treatment (ART) in Canada and other high-income countries has meant that new cases of AIDS-related infections and cancers are very rare in ART users. Nevertheless, the general risk for a wide range of cancers increases as people age.

Scientists at the U.S. National Cancer Institute (NCI) in Bethesda, Maryland, and from several U.S. universities have collaborated on a project to better understand how HIV infection could have an impact on a broad range of cancers. The team analysed health-related information captured in a cancer database. Their analysis focused on information from more than 14,000 HIV-positive people and six million HIV-negative people, all of whom were diagnosed with cancer.

The scientists found that HIV-positive people were generally more likely to be diagnosed with an advanced stage of cancer (more and bigger tumours) compared to HIV-negative people. Furthermore, HIV-positive people also had reduced chances of survival compared to HIV-negative people with the same cancer diagnosis. The scientists were largely able to rule out healthcare-related factors as a cause of these unfortunate outcomes. Instead, they suggested that HIV was likely responsible for the worse prognosis.

Study details

Scientists accessed the NCI database (NCDB) for information on people diagnosed with cancers between 2004 and 2014. They focused on data from the following people:

  • 14,453 HIV-positive people
  • 6,368,126 HIV-negative people

The scientists sought information on the following 14 sites affected by cancer:

  • anus
  • bladder
  • breast (in women)
  • cervix
  • colorectum
  • kidney
  • liver
  • lung
  • mouth
  • pancreas
  • prostate
  • skin
  • stomach
  • thyroid

Results

In general, the scientists found that HIV-positive people were more likely to be male (64% men, 36% women), younger and have a lower income than HIV-negative people.

Common cancer diagnoses were distributed as follows:

HIV-positive people

  • lung cancer – 29%
  • colorectal cancer – 14%
  • prostate cancer – 11%

HIV-negative people

  • breast cancer – 23%
  • prostate cancer – 18%
  • lung cancer – 18%

The scientists stated that HIV-positive people were “significantly more likely to be diagnosed with advanced stage cancers [affecting the following sites]”:

  • breast
  • liver
  • mouth
  • prostate
  • skin
  • thyroid

They also stated that “HIV was associated with elevated [risk of death] after a cancer diagnosis for 13 of 14 cancer sites evaluated, including an almost doubling and tripling of mortality for female breast and thyroid cancers, respectively. The persistence of these associations after adjustment for factors related to the receipt of healthcare provides support for a biological link between HIV-related immunosuppression and cancer progression.”

An exception to the trends above occurred in relation to anal cancer. According to the scientists, HIV-positive people “were substantially more likely to be diagnosed with less advanced anal cancers compared with their HIV-negative counterparts. This potentially represents an example of increased healthcare being directed towards the [HIV-positive] population, a distinct possibility given the ongoing targeting of anal cancer screening procedures to HIV-infected men who have sex with men.”

Missing data

The scientists relied on information in a cancer care database. Unfortunately, they did not have information on the HIV history of participants, including at least the following:

  • length of time living with HIV
  • lowest-ever CD4+ cell count
  • CD4+ count and viral load shortly before or at the time of diagnosis
  • classes of HIV treatments used

Such information could have provided a degree of additional insight into the health of HIV-positive people prior to the diagnosis of cancer.

The limits of ART

When used as prescribed and directed, ART is highly effective at suppressing the amount of HIV in the blood. Once viral suppression is achieved, the immune system begins to effect repairs. The benefits of ART are so profound that doctors and scientists increasingly expect many ART users to have near-normal life expectancy.

However, ART does not cure HIV infection and can only partially restore the immune system. CD4+ cell counts usually increase significantly in ART users, and this prevents AIDS. But many other teams of scientists have discovered that subtle injury to the immune system remains despite many years of good adherence to ART. The cause of this subtle injury to the immune system is uncertain. Perhaps one or more of the following issues cause such immunological injury:

  • the presence of residual HIV in the lymph nodes, spleen and other parts of the immune system
  • low levels of some germs—such as bacteria or fungi or proteins associated with these germs—enter the circulation via the gut and persist in the body. The concentration of these germs and/or their proteins are not sufficient to cause obvious infection but are enough to cause chronic activation of the immune system, gradually degrading it.
  • co-infection with a common member of the herpes virus family called CMV (cytomegalovirus)

It is important to note that the subtle injury to the immune system mentioned here is insufficient to cause AIDS to (re)appear, but it may be just enough to gradually weaken the immune system’s ability to detect and destroy some tumours. This does not mean that all or even a majority of ART users will ultimately get cancer. However, the study does suggest that the risk for unfavourable outcomes with cancer is increased among HIV-positive people.

Another group at heightened risk for cancer is people who have transplanted organs. Such people require regular use of transplant drugs to partially suppress their immune systems so that the transplanted organs survive.

All of this information taken together suggests the possibility that HIV itself may play a role in the issues that the cancer scientists found in the present study.

For the future

The present study underscores the need for HIV-positive people to get cancer screening as part of their overall health maintenance. If diagnostic tests uncover cancer, swift referral to care and treatment should be the standard. Although not mentioned by the research team, by flagging immune suppression as an issue, the study provides a rationale for considering studies testing immune therapy for cancer. In the past decade, several drugs that work by removing blocks (or check points) from the immune system of cancer patients have been tested in HIV-negative people with cancer, sometimes with prolonged remission. This class of drugs is called checkpoint inhibitors. Examples of two first-generation checkpoint inhibitors are:

  • Keytruda (pembrolizumab)
  • Opdivo (nivolumab)

Checkpoint inhibitors carry their own risks; they have unusual and sometimes intense immunologically driven side effects and they do not benefit every HIV-negative person who has taken them. Furthermore, they are very expensive. However, this does not mean that they should not be considered for large clinical trials in HIV-positive people.

Reducing cancer risk

Up until 1996, HIV infection was considered to be ultimately fatal. However, given the good news about ART, part of the burden of having a near-normal life expectancy is that more emphasis may be needed to help HIV-positive people reduce their cancer risk by doing the following:

  • speaking to a doctor about getting vaccinations against hepatitis B and HPV
  • getting help from a doctor or pharmacist to support the process of quitting smoking
  • reducing their intake of alcohol
  • if engaged in injecting or inhaling street drugs: seeking help from harm reduction organizations to minimize the risk of infection from cancer-causing viruses
  • getting screening and treatment for hepatitis C virus
  • getting advice about good dietary habits
  • learning stress management techniques
  • getting help for ways to manage anxiety, depression and other mental health issues
  • engaging in regular doctor-approved physical activity

—Sean R. Hosein

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