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CATIE - www.catie.ca

French scientists note change in rates of some cancers unrelated to AIDS

9 September 2014 - The profoundly beneficial effects of modern anti-HIV combination therapy (commonly called ART or HAART) have helped to rescue the immune systems of many HIV-positive people. In Canada and other high-income countries where access to ART is generally subsidized by health authorities, rates of AIDS-related infections and cancers have declined dramatically. As HIV-positive people can now live longer because of ART, health complications unrelated to AIDS are becoming more of an issue. One of these complications is cancer.

Researchers from across France have cooperated in collecting health-related information from HIV-positive people for a project called the French Hospital Database (FHDB). This database was started in 1989. The comprehensive data collected enables researchers to draw well-balanced conclusions.

In the latest analysis of leading non-AIDS-defining cancers from the FHDB, researchers analysed data drawn from more than 84,000 HIV-positive people, collected between 1997 and 2009, and compared these findings to results from HIV-negative people in France. They found that among HIV-positive people, the overall risk of lung and anal cancers fell over the course of the study. In this same population, rates of Hodgkin's lymphoma and liver cancer remained stable. Among HIV-positive participants whose CD4+ cell counts rose and stayed above the 500 cell/mm 3 mark, the risk for lung cancer was similar to that of the HIV-negative people. However, among HIV-positive people generally, the risk for cancers remained elevated compared to the risk among HIV-negative people.

Study details

The FHDB researchers focussed on cancers for which they had data from more than 200 HIV-positive people. Those cancers included the following:

  • anal cancer
  • lung cancer
  • Hodgkin's lymphoma
  • liver cancer

The researchers did not explore cancers that were less common because they would not have had the statistical power to draw meaningful conclusions.

In total, data from 58,525 HIV-positive men and 25,979 HIV-positive women, collected over the course of about seven years, were analysed. Most participants were between the ages of 30 and 50 years.

For information about cancer rates among HIV-negative people, researchers used data collected from France's network of cancer registries, called FRANCIM.

Results-Number of cancer diagnoses

The cancers diagnosed during the course of the study were distributed as followed:

  • anal cancer - 525 cases
  • Hodgkin's lymphoma - 433 cases
  • lung cancer - 763 cases
  • liver cancer - 535 cases

Results-Trends in new cancer diagnoses

Lung cancer

Overall, rates of new cases of lung cancer fell significantly among men regardless of their HIV status. In contrast, rates of lung cancer rose among HIV-negative women and remained stable among HIV-positive women.

Hodgkin's lymphoma

Rates of this cancer rose among HIV-negative people. However, it remained relatively stable among HIV-positive people.

Liver cancer

Rates of liver cancer rose among men regardless of their HIV status. Among HIV-positive women, rates of liver cancer increased three-fold while among HIV-negative women the increase was very slight.

Anal cancer

Rates of anal cancer did not change among HIV-positive or HIV-negative men. In contrast, rates of anal cancer rose significantly among both HIV-positive and HIV-negative women.

Risk

Although the incidence of some cancers changed over the course of the study, French scientists found that, in general the relative risk for all four cancers studied remained significantly higher in HIV-positive people compared to HIV-negative people.

For instance, the overall risk of lung cancer fell, but remained about six-fold greater in HIV-positive women and three-fold greater among HIV-positive men than among HIV-negative women and men, respectively.

The importance of CD4+ cell counts

Among participants who were taking ART and whose CD4+ counts rose above and stayed above the 500 cell mark for at least two years, the rates of lung cancer were close to those seen among HIV-negative people. However, the rate of Hodgkin's lymphoma was nine times higher and the rate of liver cancer was twice as high as the rates among HIV-negative people.

HIV, aging and cancer-is there a link?

Taking into account gender, age and HIV status, researchers found that HIV-positive people were diagnosed earlier with some cancers than HIV-negative people:

  • lung cancer - HIV-positive people seemed to be diagnosed with this cancer about three years earlier
  • liver cancer - HIV-positive people co-infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) seemed to be diagnosed with liver cancer 11 years earlier

These differences were statistically significant. However, comparing HIV-positive to HIV-negative people there was no significant difference in the age at which the following cancers were diagnosed:

  • Hodgkin's lymphoma
  • anal cancer

In the case of liver cancer, it is likely that immune dysfunction caused by HIV does accelerate the course of that cancer. In the case of lung cancer, the relatively high rates of smoking tobacco among HIV-positive people may play a role in their greater risk for lung cancer. The researchers concluded that the overall earlier occurrence of these cancers was not likely the result of accelerated aging in HIV-positive people.

Why the elevated risks?

HIV infection is associated with a marked increase in activation and inflammation in the immune system. As cells of the immune system are distributed throughout the body and within different organ systems, HIV-related inflammation affects the whole body.

ART greatly decreases HIV-related inflammation, but cannot eliminate it. Some researchers have proposed that excess HIV-associated inflammation may increase the risk of cancer. However, it is noteworthy that so far, there has not been an overall increased risk for all forms of cancer in HIV-positive people. Most of the cancers that are relatively common in this population are caused by exposure to toxins (tobacco smoke) or specific viruses (more about these viruses later) that are transmitted by sex or by sharing equipment for substance use or, in the case of some people, through exposure to contaminated blood and blood products before measures were taken to significantly improve the safety of the blood supply.

Reducing the risks of specific cancers

Although ART cannot eliminate a person's risk for developing the cancers mentioned in this report, maintaining a CD4+ cell count of at least 500 cells/mm 3 generally reduces the risk for cancer. If after several years your CD4+ count does not rise above this level, speak to your doctor about possible causes. To help preserve your immune system, it is important to begin ART shortly after a diagnosis of HIV.

Anal cancer is caused by infection with strains of human papilloma virus (HPV). There are two vaccines that help protect against HPV-Cervarix and Gardasil. The latter also provides protection against genital warts. Speak to your doctor about the possibility of getting vaccinated against HPV and also for a referral to an anal cancer screening program in your region. Using condoms when you have sex can also help reduce your risk of being exposed to HPV (and other germs).

Infection with HBV and/or HCV can cause liver cancer . Speak to your doctor about getting screened for these infections. Treatment for HBV is available and if you are not infected, so is a vaccine. Treatment for HCV is available and becoming safer, shorter and easier to tolerate. Correct and consistent use of condoms can help to reduce the risk of getting HCV during anal intercourse. There is no vaccine for HCV.

Smoking tobacco increases the risk for not only lung cancer but also other cancers. If you smoke, speak to your doctor, nurse and pharmacist about getting support for quitting smoking.

Hodgkin's lymphoma appears to be caused by infection with a common member of the herpes virus family, called Epstein-Barr virus (EBV). At this time there is no proven way to lower the risk for Hodgkin's lymphoma.

Healthier living

In observational studies, some of the interventions listed below have in some cases, been associated with a reduced risk for cancer and/or can help people lead healthier lives:

  • Maintain a healthy weight - If you are over- or under-weight, speak to your doctor.
  • Exercise several times each week - Talk to your doctor about what kind and intensity of exercise is right for you.
  • Reduce the negative effects of stress - For some people, exercise can help; for others, additional practices, such as yoga, meditation, Tai Chi and mindfulness exercises, may be useful. Counselling can also help people cope with and find ways to deal with stress. Speak to your doctor about your mental health needs.
  • Eat a diet rich in fibre, colourful fruit and vegetables.
  • Cut down on your exposure to alcohol and other substances and seek addiction support if needed - If you are addicted to alcohol or other substances, ask your doctor and nurse for help dealing with it. Addiction can degrade a person's health.
  • Avoid sharing equipment for substance use - Substance use exposes people to unhealthy chemicals and by sharing equipment, increases the risk of exposure to viruses that can cause serious illness and cancer.

-Sean R. Hosein

Resources

A Practical Guide to Nutrition - CATIE's guide to healthy eating, vitamins and supplements, and managing symptoms and side effects through nutrition

HIV and emotional wellness - CATIE's guide to how people with HIV can cultivate their emotional well-being

Mindfulness-based therapy found helpful for stress and the immune system - CATIE News

CATIE's Hepatitis C information

REFERENCES:

  1. Hleyhel M. Risk of non-AIDS-defining cancers among HIV-1-infected individuals in France between 1997 and 2009: results from a French cohort. AIDS . 2014 Sept 10;28:2109-18.
  2. May MT, Gompels M, Delpech V, et al. Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy. AIDS . 2014 May 15;28(8):1193-202.
  3. Montaner JS, Lima VD, Harrigan PR, et al. Expansion of HAART coverage is associated with sustained decreases in HIV/AIDS morbidity, mortality and HIV transmission: the "HIV Treatment as Prevention" experience in a Canadian setting. PLoS One. 2014 Feb 12;9(2):e87872.
  4. Smith CJ, Ryom L, Weber R, et al. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet . 2014 Jul 19;384(9939):241-8.
  5. Hjartåker A, Knudsen MD, Tretli S, et al. Consumption of berries, fruits and vegetables and mortality among 10,000 Norwegian men followed for four decades. European Journal of Nutrition . 2014; in press.
  6. Leenders M, Boshuizen HC, Ferrari P, et al. Fruit and vegetable intake and cause-specific mortality in the EPIC study. European Journal of Epidemiology . 2014; in press.
  7. Büchner FL, Bueno-de-Mesquita HB, Ros MM, et al. Variety in fruit and vegetable consumption and the risk of lung cancer in the European prospective investigation into cancer and nutrition. Cancer Epidemiology, Biomarkers & Prevention . 2010 Sep;19(9):2278-86.
  8. Etemadi A, O'Doherty MG, Freedman ND, et al. A prospective cohort study of body size and risk of head and neck cancers in the NIH-AARP Diet and Health Study. Cancer Epidemiology, Biomarkers & Prevention . 2014; in press .
  9. Stagl JM, Antoni MH, Lechner SC, et al. Randomized controlled trial of cognitive behavioral stress management in breast cancer: a brief report of effects on 5-year depressive symptoms. Health Psychology . 2014; in press .
  10. Chao C, Jacobson LP, Tashkin D, et al. Recreational amphetamine use and risk of HIV-related non-Hodgkin lymphoma. Cancer Causes and Control . 2009 Jul;20(5):509-16.
  11. Masiá M, Robledano C, Ortiz de la Tabla V, et al. Coinfection with human herpesvirus 8 is associated with persistent inflammation and immune activation in virologically suppressed HIV-infected patients. PLoS One . 2014 Aug 18;9(8):e105442.
  12.  Roerecke M, Rehm J. Cause-specific mortality risk in alcohol use disorder treatment patients: a systematic review and meta-analysis. International Journal of Epidemiology. 2014 Jun;43(3):906-19.

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From Canadian AIDS Treatment Information Exchange (CATIE). For more information visit CATIE's Information Network at http://www.catie.ca

Source: CATIE: CANADIAN AIDS TREATMENT INFORMATION EXCHANGE


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