Large and long French study explores changes in cancer risk among people with HIV

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CATIE News 01152026
  • A study of more than 150,000 people with HIV found cases of some cancers are declining
  • Researchers credit the decline from 1997 to 2018 to HIV treatment improving immune function
  • Cancer risk still remained higher for people living with HIV than HIV-negative people

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If left untreated, HIV can impair the functioning of the immune system, leading to its gradual decline and the appearance of life-threatening infections and cancers. Since 1996, effective treatment for HIV (ART; antiretroviral therapy) has been increasingly available in Canada and other high-income countries. When used as directed, ART can reduce the amount of HIV in the blood to the point where it usually cannot be detected with routine laboratory tests. This suppression of HIV allows the immune system to mostly repair the injury caused by HIV. The result is that for most adherent ART users, the risk of AIDS-related complications declines dramatically. In fact, many studies project that a large proportion of ART users will have a life expectancy similar to that of the average HIV-negative person.

A changing internal environment

As people with HIV live longer, they become at risk for aging-related issues—typically, type 2 diabetes, high blood pressure, arteriosclerosis, and so on. Another consequence of aging is that cells can accumulate changes (mutations) to their genes. Some of these changes are unfavourable; they increase the risk for cells to follow a development pathway that leads to abnormal cellular growth and heightens the potential for the formation of pre-cancers and cancers.

The immune system plays an important role in detecting and eliminating abnormal and pre-cancerous cells (as well as cancers). However, as everyone ages (regardless of HIV status), their immune systems become slightly weaker and less effective at eliminating pre-cancers and cancers. 

Thus, it is important to conduct long-term studies of ART users to monitor their risks for different cancers. Findings from such studies can help inform care guidelines for people with HIV.

In France

A team of researchers from 184 clinics in France collected health-related information from people using ART. In the past, the French Hospital Database has produced useful reports, as it has detailed records. 

The latest analysis from the database focused on cancer risk in ART users. It used information from 154,733 people that was collected between January 1997 and December 2018. Participants were between 18 and 84 years old.

The researchers compared their findings to those from about 20% of the French population that did not have HIV, some of whom also developed cancer within the study period.

The French researchers focused on the cancers below, which they grouped as follows:

AIDS-defining cancers related to viruses

  • Kaposi’s sarcoma – caused by the Kaposi’s Sarcoma Herpes Virus (KSHV), also known as Human Herpes Virus-8 (HHV-8)
  • non-Hodgkin lymphoma – caused by the Epstein-Barr Virus (EBV)
  • invasive cervical cancer – caused by some strains of human papillomavirus (HPV)

Non-AIDS-defining cancers related to viruses

  • Hodgkin lymphoma – some cases appear to be caused by EBV infection
  • liver cancer – caused by the hepatitis B virus (HBV) or hepatitis C virus (HCV)
  • anal cancer – caused by some strains of HPV

Cancers unrelated to viruses

  • lung cancer
  • colorectal cancer
  • prostate cancer
  • breast cancer

Results

Overall trends

During the study, there were some general trends among people with HIV, as follows:

  • The proportion of people who injected drugs decreased. The researchers did not provide an explanation for this. 
  • The proportion of people coinfected with hepatitis B or hepatitis C virus fell by about 50%. The researchers attribute this decline to the use of antiviral drugs designed to suppress hepatitis B and cure hepatitis C. 
  • There was a marked increase in the proportion of people with a CD4+ count of at least 500 cells/mm3; by the end of the study, about 53% of males and 65% of females had high CD4+ counts. 
  • The CD4/CD8 ratio is one way to assess the overall health of the immune system. A ratio of 1.0 or more is generally found in healthy HIV-negative people. In the present study, the proportion of participants with a CD4/CD8 ratio of 1.0 or greater increased from 5% to at least 30%.
  • The proportion of participants with a suppressed viral load (in this case less than 500 copies/mL) increased from about 30% to 90% regardless of gender. 

Changes in cancer risk

Over the course of the study, researchers found that cases of the following cancers fell in people with HIV: 

AIDS-defining cancers related to viruses

  • Kaposi’s sarcoma 
  • non-Hodgkin lymphoma 
  • invasive cervical cancer 

Non-AIDS-defining cancers related to viruses

  • Hodgkin lymphoma 
  • liver cancer 
  • anal cancer 

However, the overall chance of developing these cancers remained elevated among people with HIV compared to the population of people without HIV in France, even in the most recent period of the study (2013 to 2018).

Cases of prostate and colorectal cancer increased over time, while rates of breast cancer remained stable. When researchers further analyzed these three cancers and compared rates in both populations (people with HIV and people without HIV), they found that the risk for developing prostate, colorectal or breast cancer remained “stable and similar.” 

Among people with HIV who achieved a CD4+ count of at least 500 cells/mm3, the researchers stated that “the risks of most virus-related cancers remained elevated but was lower than in people with HIV [who did not have as high CD4+ cell counts].”

Also, in people with a CD4+ count of at least 500 cells/mm3, researchers stated that the risk for lung and cervical cancer were “similar to the general population.”

Bear in mind

The researchers stated that the reasons for the decline of many cancers in people with HIV was likely due to the “beneficial effect of ART and restored CD4+ cell counts,” particularly on virus-related cancers. 

However, risk remained for some cancers. According to the researchers, part of the reason there may still be a high overall cancer risk for some people with HIV in the study is that an estimated 27% of people with HIV in France have low CD4+ counts (less than 200 cells/mm3) because of late initiation of ART. The researchers noted that this proportion of people with HIV who have low CD4+ cell counts has been relatively stable since 2012. They stated that people with less than 200 CD4+ cells/mm3 had “a significant proportion of virus-induced cancers.”

The researchers noted that there was a “strong reduction of liver cancer in HBV/HCV coinfected people with HIV,” particularly in the last period of the study (2013 to 2018). During that time, potent treatments for HCV would have become available. More people with HBV were possibly screened and treated for this infection. However, much work remains to be done when it comes to screening and treating people who are coinfected with these viruses.

In addition, among males with HIV, the researchers found an increase of liver cancer unrelated to viral infections. They infer that this may be caused by an increase in fat accumulation in the liver. This can occur in people with pre-diabetes or diabetes, obesity and other metabolic issues. The excess fat in the liver causes inflammation, injury and scarring of this vital organ. In turn, the increase in scar tissue leads to an increased risk for liver cancer. Reports of this problem are also occurring among people without HIV as obesity rates rise.

The researchers stated that reductions in anal and cervical cancer were likely due to better general immunity (from prolonged use of ART) as well as screening programs for these cancers. 

The study’s findings on prostate, colorectal and breast cancer were interesting. Overall, the number of people with HIV who developed these cancers increased during the study. The researchers stated that this increase occurred because of aging. However, it is important to recall that the researchers described the risk for these cancers in people with HIV and without HIV as “stable and similar.” Nevertheless, the researchers underscored the importance of screening for these cancers among people with HIV.

Reducing cancer risk

Recent research suggests that, in general, cancer is a growing problem worldwide. Everyone’s cancer risk is different and dependent on multiple issues, such as behaviour, diet, socioeconomic status, genetics and other factors. Some risk factors can be modified, but others (such as one’s family history or genetics) cannot. Focusing on risks that can be modified and reducing such risks can generally lead to better overall health and, likely, reduced chances of developing cancer.

The following lists include tips for better health in general and ideas about cancer prevention and screening that can be discussed with a healthcare professional. These lists are not comprehensive.

General health tips:

  • Get help for cutting down and ultimately quitting smoking.
  • Get help for reducing alcohol intake.
  • Consult with a harm reduction organization if you use drugs to learn about ways to reduce the risk of exposure to hepatitis C virus (and other germs).
  • Maintain a healthy weight. Speak to your doctor or nurse for help in achieving a weight that is optimal for you.
  • Engage in regular exercise. Speak to your doctor or nurse about what type of exercise is right for you.
  • Eat a diet rich in colourful fruits and vegetables (including cruciferous vegetables).

Cancer prevention and screening:

In general, screening for breast, colon and prostate cancer is routinely done in many high-income countries, depending on age and other factors. Specific groups may consider discussing one or more of the following additional interventions with a doctor or nurse:

  • screening for diseases related to human papillomavirus and discussion of HPV vaccination
  • screening for hepatitis B and C viruses, and, if necessary, treatment; a vaccine for hepatitis B is available to prevent infection with this virus
  • people with a history of smoking can find out about the availability of lung cancer screening

Resources

Six-month study finds exercise and stretching beneficial for brain and body in people with HIV – CATIE News

Large U.S. study explores risk of cancers in people with HIV – CATIE News

Swiss researchers encourage prevention and treatment of cardiovascular disease and cancer as people with HIV live longer – CATIE News

Preventing anal cancer: The importance of HPV vaccination for gay, bisexual and other men who have sex with men – Prevention in Focus

Ontario study looks at trends in cancer in people with HIV – CATIE News

French researchers investigate second cancers in people with HIV who survived a first cancer – CATIE News

Ontario study links low T-cell counts to increased risk for certain cancers in people with HIV – CATIE News

North American study finds low CD4/CD8 ratio can help predict cancer risk in people with HIV – CATIE News

Second cancer risk after surviving Hodgkin’s lymphoma in people with HIV – CATIE News

Trends in liver cancer among HIV-positive people in North America – CATIE News

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