French Study Finds Increased Anal Cancer Risk Despite ART

HIV attacks the immune system, causing it to become increasingly weak and dysfunctional. Treatment with combinations of potent anti-HIV drugs (commonly called ART or HAART) greatly reduces production of HIV in the body. As less HIV is produced, the immune system can begin repairs. These repairs are generally sufficient to keep AIDS-related infections at bay. However, because defects in immunity persist, there is an elevated risk for certain cancers in some ART users. The degree of this elevated cancer risk varies from one HIV-positive person to another and arises from a complex intersection of factors, likely including some of the following:

• prolonged exposure to proteins produced by HIV-infected cells
• persistent inflammation incited by HIV infection (such inflammation is only partially reduced by ART)
• certain behaviours, such as smoking tobacco, excessive intake of alcohol and/or use of other substances
• insufficient exercise
• obesity
• co-infection with certain viruses

Viruses and Cancer

Due to similar routes of transmission, some HIV-positive people are also infected with other viruses. Some of these viruses can cause cells to develop abnormally. Such abnormal cells can transform into pre-cancers and, in some cases, even cancer. Some viruses with this cancer-causing potential include the following:

• HBV (hepatitis B virus) and HCV (hepatitis C virus) -- these infect and damage the liver and increase the risk for liver cancer
• EBV (Epstein-Barr virus) -- a member of the herpes virus family, EBV has been linked to the development of a cancer of the immune system called lymphoma
• HHV-8 (human herpes virus-8) -- another member of the herpes virus family, HHV-8 can cause Kaposi's sarcoma (KS) and is linked to a cancer-like condition called Castleman disease
• HPV (human papillomavirus) -- some strains of HPV can cause ano-genital warts; other strains can cause cancer of the anus and penis in men and cancers of the anus, cervix and vulva in women. Emerging research suggests that some strains of HPV may be linked to cancers of the mouth, lips and throat.

Anal Cancer and Risk

Researchers have found that in the time before ART became available, cases of anal cancer were twice as high among HIV-positive men who have sex with men (MSM) compared to HIV-negative MSM.

Furthermore, compared to the average HIV-negative man, the relative risk of anal cancer is many times greater for HIV-positive men who are not MSM (37-fold) and even greater for HIV-positive MSM (60-fold).

Anal Cancer Risk and ART

Some studies have found no reduction in the risk of anal cancer among HIV-positive people in the current era in places where ART is widely available. In contrast, two studies suggest a decreased risk of this cancer with prolonged use of ART. However, what all studies of anal cancer in high-income countries in the current era have in common is that cases appear to be increasing compared to the time before ART was available.

Most studies comparing anal cancer risk among HIV-positive people have involved a relatively small number of cases -- between 18 and 80. Such studies did not generally account for factors such as the following:

• different sub-populations of HIV-positive people
• different degrees of immunodeficiency

Also, most of these studies could not clearly conclude whether anal cancer was occurring at a younger age in HIV-positive people compared to HIV-negative people.

The French Hospital Database

To address this and other issues, researchers in France conducted an analysis of their database, which has collected health-related information from nearly 110,000 HIV-positive people. The researchers also compared the data on HIV-positive people with that from HIV-negative people with anal cancer.

Surprisingly, in their report, the French team found no significant difference in the relative risk for anal cancer in the pre-HAART era (1992 to 1996) and the HAART-era (1997 to 2008). Furthermore, no differences in anal cancer risk were found in the early HAART era (1997 to 2000) and the later HAART era (2005 to 2008). Additional findings from this important study appear later in this CATIE News bulletin, along with steps on how to reduce anal cancer risk.

Study Details

The French Hospital Database has collected health-related information on 109,771 HIV-positive people from 69 clinics in hospitals across France.

For purposes of comparison, the researchers obtained information on anal cancer cases in HIV-negative people from a database called FRANCIM (France-cancer-incidence et mortalité). That database contained information collected from about 12 million people.

In the present study, the analysis on anal cancer focused on the period between January 1992 and December 2008.

Results -- Distribution of Anal Cancer

Over the 16 years of the study, cases of anal cancer were distributed as follows:

HIV-Positive People: 263 Cases

• men -- 91% of cases; average age at cancer diagnosis was 46 years
• women -- 9% of cases; average age at cancer diagnosis was 42 years

HIV-Negative People: 2,012 Cases

• men -- 29% of cases; average age at cancer diagnosis was 67 years
• women -- 71% of cases; average age at cancer diagnosis was 72 years