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California study underscores the need to reduce cancer risk

30 January 2012 - HIV infection weakens the immune system and makes people vulnerable to life-threatening infections and certain cancers. However, potent combination anti-HIV therapy, commonly called ART or HAART, reduces production of HIV and allows the immune system to partially recover. For the average person in Canada and other high-income countries who becomes HIV-positive today and who adheres to and responds to ART, AIDS-related infections should no longer be a problem.

However, some HIV-induced defects in the functioning of the immune system persist despite the use of ART. For instance, continuous immune system activation and inflammation occurs even under treatment. Another issue is that HIV-positive people are often co-infected with other viruses that have the ability to cause abnormal development of cells, in some cases causing affected cells to transform into pre-cancers and cancers. Some of these co-infections include the following:

  • EBV (Epstein-Barr Virus) - a member of the herpes virus family that has been linked to an increased risk for non-Hodgkin's lymphoma
  • HHV-8 (human herpes virus-8) - a member of the herpes virus family that can cause Kaposi's sarcoma
  • HPV (human papilloma virus) - some strains of this virus can cause ano-genital warts, others can cause cancer of the anus, cervix, penis and mouth/throat
  • hepatitis B and hepatitis C viruses (HBV and HCV) - these infect and damage the liver and greatly increase the risk for liver cancer

The combination of persistent activation and ongoing inflammation and the presence of viruses associated with tumours and perhaps other unknown factors may place some HIV-positive people at heightened risk for cancer.

Cancer study in California

Researchers in California have conducted a very large study monitoring the health of 20,000 HIV-positive people for the presence of 10 different cancers. What made their study different from others is that health-related data from each HIV-positive participant was matched with health-related data from 10 HIV-negative people of similar age, ethnicity/race, gender, geographic location and similar risk factors such as use of alcohol, tobacco and other substances and the presence or absence of obesity. In contrast, most cancer studies that have been done tend to compare HIV-positive people to an idealized HIV-negative person without such risk factors. This may cause some studies to draw incorrect conclusions.

The California researchers found that among HIV-positive people the risk for some cancers was elevated, though in some cases low CD4+ counts played a role in intensifying susceptibility to cancer.

Study details

The average profile of HIV-positive participants at the time they entered the study was as follows:

  • 91% men, 9% women
  • age - 41 years
  • hepatitis C virus co-infection - 8%
  • hepatitis B virus co-infection - 5%
  • past use of tobacco - 43%
  • diagnosis of alcohol abuse - 11%
  • diagnosed as being overweight or obese - 38%
  • CD4+ cell count - 400 cells
  • HIV viral load - 50,000 copies/ml

Participants began to enroll in 1996 and remained in the database until they developed cancer or until 2009.

Results

In general, the lower the CD4+ cell count, the greater the risk of cancer, particularly for the following cancers:

  • Kaposi's sarcoma (KS)
  • non-Hodgkin's lymphoma (NHL)
  • Hodgkin's lymphoma (HL)
  • anal cancer
  • cancers of the colon and rectum

In HIV-positive people whose CD4+ cell counts were 500 cells or greater, the risk of having these cancers was reduced compared to people with lower CD4+ cell counts. However, even among people with 500 or more CD4+ cells, the risk for these cancers was still elevated compared to HIV-negative people of similar age, gender, ethnicity and so on, as follows:

  • KS - 60-fold increased risk
  • NHL - four-fold increased risk
  • anal cancer - 34-fold increased risk
  • HL - 14-fold increased risk

HIV-positive people who had less than 200 CD4+ cells had an elevated risk for cancers affecting the following tissues:

  • lungs
  • colon and rectum
  • mouth and throat

People who had less than 500 CD4+ cells were at increased risk for skin and liver cancers.

The California researchers found that HIV-positive people were at increased risk for six of the 10 cancers (KS, NHL, HL, skin cancer, liver cancer, anal cancer) whether or not they had several cancer risk factors. Possible explanations for this are that HIV infection-even with the use of ART-is associated with continuing low-level defects in the functioning of the immune system and, co-infection with sexually transmitted viruses (some of which can cause cancer) is relatively common in HIV-positive people.

Risk factors and certain cancers

Initial analyses suggested that HIV-positive people appeared to be at increased risk for cancers of the mouth, throat and lungs, but after researchers took into account what they called "smoking, alcohol/drug abuse" and being overweight or obese, this apparent elevated risk due to HIV infection disappeared. A recent Swiss study has found that lung cancer among HIV-positive people was also associated with tobacco use.

Thus, the elevated rates for cancers of the mouth, throat and lungs previously reported in several other studies are more likely to have arisen because of exposure to cancer-causing chemicals in tobacco smoke and alcohol (and perhaps other substances) and not because of HIV infection.

There was also an intersection of cancer risk factors in the present study, with people who were diagnosed as having engaged in what the researchers called "alcohol/drug abuse" being more likely (61%) to smoke tobacco compared to people who did not have such a diagnosis of substance use (26%).

The elevated risk for liver cancer in this study is likely due to co-infection with hepatitis-causing viruses.

As with previous studies, HIV-positive men in the California study were at decreased risk for prostate cancer. The reason(s) for this is not clear.

Weaknesses and strengths

No study is perfect and the California study had several weaknesses, such as the following:

  • Information about cancer risk factors was obtained from medical records rather than from interviews or surveys with participants (people do not always disclose their behaviours to their doctors).
  • The duration of substance use was not clear from these records and therefore could not be analysed.
  • Information confirming HPV infection was not available.
  • Despite having a large group of participants (20,000) with HIV, the researchers were not able to draw firm conclusions about the risk for many other, less common cancers.
  • The proportion of women in this study was small.

Yet, even though there were weaknesses, the study had some important strengths, such as these:

  • its large size
  • matching HIV-positive people to demographically similar HIV-negative people
  • use of cancer registries to confirm diagnoses

Due to these strengths, the researchers were able to produce a relatively robust report. Moreover, their findings on lung cancer were supported by the previously mentioned Swiss study.

What can be done?

Based on the results of the California study, the following steps would likely be beneficial for HIV-positive people to help reduce their cancer risk:

Early therapy

Initiating ART when the CD4+ count is 500 cells or more would probably greatly decrease the risk for subsequently developing cancer. Some leading researchers and clinicians increasingly favour the early initiation of ART because of this and other beneficial effects.

Substance use and its drivers

Reducing exposure to factors associated with cancer (such as tobacco smoke, excessive alcohol and injection drug use) would be a good step. Another important step would be getting help for the mental and emotional health conditions that often underpin some people's susceptibility to addictive behaviours and substance use.

Vaccinations and treatment for hepatitis-causing viruses

Although there is not a vaccine for hepatitis C virus, a vaccine for hepatitis A and B viruses is available. Treatment is available for hepatitis B and C infections.

Safer sex

This reduces exposure to germs that can harm HIV-positive people, including herpes viruses, HPV, HBV and HCV.

Regular medical check-ups

People with HIV are susceptible to certain cancers. Medical check-ups should include screening for such cancers.

-Sean R. Hosein

REFERENCES:

  1. Cobucci RN, Saconato H, Lima PH, et al. Comparative incidence of cancer in HIV-AIDS patients and transplant recipients. Cancer Epidemiology . 2012; in press .
  2. Downey JS, Attaf M, Moyle G, et al. T-cell signalling in antiretroviral-treated, aviraemic HIV-1-positive individuals is present in a raised state of basal activation that contributes to T-cell hyporesponsiveness. AIDS . 2011 Oct 23;25(16):1981-6.
  3. Appay V, Almeida JR, Sauce D, et al. Accelerated immune senescence and HIV-1 infection. Experimental Gerontology . 2007 May;42(5):432-7.
  4. Herbeuval JP, Nilsson J, Boasso A, et al. HAART reduces death ligand but not death receptors in lymphoid tissue of HIV-infected patients and simian immunodeficiency virus-infected macaques. AIDS . 2009 Jan 2;23(1):35-40.
  5. Boasso A, Royle CM, Doumazos S, et al. Overactivation of plasmacytoid dendritic cells inhibits antiviral T-cell responses: a model for HIV immunopathogenesis. Blood . 2011 Nov 10;118(19):5152-62.
  6. Reepalu A, Blomé MA, Björk J, et al. The risk of cancer among persons with a history of injecting drug use in Sweden-a cohort study based on participants in a needle exchange program. Acta Oncologica . 2012 Jan;51(1):51-6.
  7. Chao C, Jacobson LP, Tashkin D, et al. Recreational amphetamine use and risk of HIV-related non-Hodgkin lymphoma. Cancer Causes & Control . 2009 Jul;20(5):509-16
  8. Shebl FM, Engels EA, Goedert JJ. Opportunistic intestinal infections and risk of colorectal cancer among people with AIDS. AIDS Research and Human Retroviruses . 2012; in press .
  9. Grulich AE, Jin F, Poynten IM. HIV, cancer and aging. Sexual Health . 2011 Dec;8(4):521-5.
  10. Gucalp A, Noy A. Spectrum of HIV lymphoma 2009. Current Opinion in Hematology . 2010 Jul;17(4):362-7.
  11. Marcucci F, Mele A. Hepatitis viruses and non-Hodgkin lymphoma: epidemiology, mechanisms of tumorigenesis and therapeutic opportunities. Blood. 2011 Feb 10;117(6):1792-8.
  12. Mehanna H, Beech T, Nicholson T, et al. Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer-systematic review and meta-analysis of trends by time and region. Head & Neck . 2012; in press .
  13. Silverberg MJ, Chao C, Leyden WA, et al. HIV infection, immunodeficiency, viral replication and the risk of cancer. Cancer Epidemiology, Biomarkers & Prevention . 2011 Dec;20(12):2551-9.
  14. Clifford GM, Lise M, Franceschi S, et al. Lung cancer in the Swiss HIV Cohort Study: role of smoking, immunodeficiency and pulmonary infection. British Journal of Cancer . 2012; in press .

###

CATIE-News is written by Sean Hosein, with the collaboration of other members of the Canadian AIDS Treatment Information Exchange, in Toronto.

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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