French Study Finds Increased Anal Cancer Risk Despite ART

December 19, 2012

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Rates of new cases of anal cancer were highest among HIV-positive MSM, followed by what the researchers called "other" HIV-positive men, and then HIV-positive women.

Risk Factors Linked to Anal Cancer Among HIV-Positive People

Anal cancer was more likely to occur among HIV-positive people with the following profile:

  • older participants, "particularly MSM," noted the researchers
  • participants who had been diagnosed with AIDS
  • participants with a lower nadir (lowest-ever) CD4+ cell count

The risk of anal cancer nearly tripled in the current era compared to the pre-HAART era. This likely arose because of differences in survival. For instance, in the pre-HAART era, participants were much more likely to die at a younger age from complications stemming from an AIDS-related infection. In the HAART era, in high-income countries, such complications are no longer common. This means that people live longer with both HIV and HPV infection, which allows more time for tumours to develop. In the present era, thanks to HAART, HIV-positive people likely feel better, and so interest in sex returns. This leads to resurgence in sex, which may also mean more exposure to strains of HPV that are associated with tumours.

Having a high CD4+ cell count did not seem to be protective from anal cancer because cases of anal cancer were documented even among HIV-positive people whose CD4+ counts were greater than 500 cells. Furthermore, among participants whose CD4+ cell counts were greater than 500 cells for two years before the diagnosis of anal cancer, their risk for this cancer was 20-fold greater than among HIV-negative people.

More Trends -- Limitations to HAART

The researchers found that all sub-groups of HIV-positive people experienced an increase in diagnoses of anal cancer after ART became available. Although the rate of anal cancer among HIV-positive people in France has stabilized in the current era, according to French researchers it remains very high compared to that seen in HIV-negative people.

Montréal researcher François Coutlée, MD, has also been studying HPV and has reviewed studies comparing HPV-related disease in the pre-HAART and HAART eras. In a recent article in the journal Sexual Health, Dr. Coutlée wrote: "If HAART was truly protective against [HPV-related pre-cancers, new cases of anal cancer] would be decreasing, which is not what is being observed."

Specific Risks per Group

The French study uncovered a high risk of anal cancer among HIV-positive people, particularly in men and especially MSM. The risk of anal cancer in the current era among HIV-positive people compared to HIV-negative people was as follows:

  • HIV-positive MSM -- 100-fold greater risk than the average HIV-negative male
  • HIV-positive non-MSM -- 50-fold greater risk than the average HIV-negative male
  • HIV-positive women -- 13-fold greater risk than the average HIV-negative woman

Possible Explanations for Elevated Risk

Researchers in both France and the U.S. have sought explanations for the excessive risk of anal cancer seen in HIV-positive people. One possibility is that MSM and others at high risk for HIV infection may become infected with cancer-causing strains of HPV at an earlier age than HIV-negative people. This may allow HPV-infected cells more time to develop abnormally, thus a greater risk of developing pre-cancer and cancer.

In general, the immune system becomes less effective as people age and there is a suggestion that viral infections, particularly those caused by CMV (cytomegalovirus, a member of the herpes family of viruses), may prematurely age the immune system. Added to this is the burden of HIV infection, which is associated with hints of acceleration in the aging of the immune system. Being co-infected with different viruses may weaken the immune system's ability to contain and control the growth of pre-cancers and tumours.

Theories and evidence for accelerated aging of the immune system in the context of HIV infection are somewhat controversial and require further research.

Earlier HIV Therapy

In most high-income countries the threshold for starting ART is at least 350 cells. In cases where symptom-free HIV-positive people have co-existing health issues -- including conditions that affect major organs such as the brain, heart, liver and kidneys -- treatment may be recommended or encouraged at higher CD4+ count thresholds, even if a person has more than 500 cells. In such cases, treatment helps to strengthen the immune system and reduce HIV-related inflammation and the risk of damage to organ-systems caused by HIV and/or co-infections.

A key risk factor for anal cancer in the French study was having a low nadir CD4+ cell count. On average, 50% of HIV-positive participants who developed anal cancer had a nadir CD4+ count less than 95 cells.

The French researchers stated that if more HIV-positive people initiated ART at relatively high CD4+ counts, then fewer people would experience low nadir CD4+ cell counts and would therefore be at greatly reduced risk for the subsequent development of anal cancer.

Researchers in Québec have also found that a low nadir CD4+ count is associated with an increased risk for anal pre-cancer and cancer among HIV-positive men.

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This article was provided by Canadian AIDS Treatment Information Exchange. Visit CATIE's Web site to find out more about their activities, publications and services.

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