- HIV treatment can greatly strengthen the immune system but some weakness may persist
- A French study found that 9% of people with HIV who survived an initial cancer subsequently developed a new cancer
- Programs need to be designed and tested to help HIV-positive people reduce their cancer risk
Cases of some cancers were prominent in the first 15 years of the HIV pandemic. In that era, common cancers associated with HIV included the following:
- Kaposi’s sarcoma – caused by human herpes virus 8 (HHV8)
- non-Hodgkin’s lymphoma – caused by Epstein-Barr virus (EBV)
- invasive cervical cancer – caused by human papillomavirus (HPV)
These three cancers are lumped together as AIDS-defining cancers because historically their presence in HIV-positive people suggested profound immune deficiency.
In 1996, in Canada and other high-income countries, potent HIV treatment (ART) became available. ART was able to suppress levels of HIV in the blood. This suppression allowed the immune system to repair itself sufficiently so that the risk of AIDS-related infections and cancers became very rare.
Researchers predict that, based on data collected since 1996, many ART users are likely to have a near-normal life expectancy. However, ART cannot resolve all issues, and it is plausible that over time a minority of people will become at increased risk for cancer for at least the following reasons:
Some people with HIV are co-infected with other viruses known to cause cancer. Such viruses include hepatitis B and C, which infect the liver and increase the risk for liver cancer; strains of HPV that can cause cancer of the anus, cervix, mouth, lips, throat, penis and vulva; and Epstein-Barr virus, a member of the herpes virus family that increases the risk for some forms of lymphoma.
Surveys have found that a relatively high proportion of people with HIV smoke tobacco. Smoking tobacco is responsible for many cancers. According to the U.S. National Cancer Institute, tobacco smoking causes the following: “cancer of the lung, larynx (voice box), mouth, esophagus, throat, bladder, kidney, liver, stomach, pancreas, colon and rectum, and cervix, as well as acute myeloid leukemia.”
The National Cancer Institute has stated that the greater the amount of alcohol consumed, the greater the risk for cancers affecting the following parts of the body: “mouth, throat, esophagus, larynx (voice box), liver, and breast.”
HIV infection is associated with higher-than-normal levels of inflammation and immune activation. ART reduces but does not normalize these issues. It is at least plausible that chronic inflammation and excess immune activation may modestly weaken or age the immune system. Excess inflammation could also increase the risk for the formation of abnormal cell development, leading to pre-cancer and cancer.
CMV co-infection is relatively common among people with HIV. Some researchers in Canada suggest that CMV can accelerate the aging of the immune system and also contribute to excess inflammation and immune activation.
Researchers in France have been collecting health-related information from people with HIV for a database called Dat’AIDS. The database began enrolling participants as early as 1983 and periodically in subsequent years. Dat’AIDS has amassed information on almost 45,000 people. From time to time, researchers analyze the information in the database and produce useful reports.
A recent analysis from Dat’AIDS focused on people who survived an initial occurrence of cancer. Researchers found that 9% of participants who survived their first cancer went on to develop a second, different (new) form of cancer, which is referred to as a “second primary cancer”. Many of the people who developed a second new cancer had a very low CD4+ count in the past (less than 200 cells/mm3) and had long-standing HIV infection, diagnosed prior to 1996.
The French researchers stated that “second primary cancers are now a major concern in HIV-positive cancer survivors, justifying the development of monitoring strategies after a first cancer.”
Researchers reviewed health-related information collected from 17 major clinics in France. Participation recruitment began in 1983 and the data were analyzed to the end of 2015.
The researchers divided cancers into the following three groups:
- AIDS-defining cancers – Kaposi’s sarcoma, non-Hodgkin’s lymphoma and invasive cervical cancer
- virus-related non-AIDS-defining cancers – including those caused by hepatitis B and C viruses, HPV, EBV (this can cause Hodgkin’s lymphoma) and Merkel cell polyomavirus (this can cause Merkel cell cancer)
- all other cancers
A brief profile of participants at the time they entered the cancer analysis was as follows:
- 83% men, 17% women
- age at first cancer – 46 years
- first cancer occurred in 1996 or earlier – 22%
- first cancer occurred after 1996 – 78%
- 77% had a CD4+ count below the 200-cell/mm mark at some point in the past prior to initiating ART, indicating profound immune deficiency
- 60% were diagnosed with HIV prior to 1996
- 16% were co-infected with HCV
- 9% were co-infected with HBV
- 32% were past smokers and 37% were current smokers
On average, participants were monitored for nine years.
Out of the 44,642 people in Dat’AIDS, 444 (9%) developed one cancer and then later a second cancer that was different from the first one.
At the end of the study period, the distribution of participants who developed cancer was as follows:
- alive – 55%
- deceased – 35%
- lost contact with their clinic – 10%
The average age at the time of first primary cancer (that is, the cancer was new and not a recurrence or spread of another cancer) was 46 years.
The distribution of first primary cancers was as follows:
- AIDS-defining cancers – 269 people
- virus-related non-AIDS-defining cancers – 51 people
- all other cancers – 124 people
The average age at the time of second primary cancer was 51 years. On average, people developed a second cancer four years after the first one was diagnosed; this did not differ by gender.
The distribution of second primary cancers was as follows:
- AIDS-defining cancers – 130 people
- virus-related non-AIDS-defining cancers – 85 people
- all other cancers – 229 people
Comparing the first and second cancers, one can see that AIDS-related cancers comprised a majority of first cancer, while “all other cancers” were more common in cases of second cancer.
Types of second cancer
The most common second cancers were distributed as follows, in descending order:
- non-Hodgkin’s lymphoma
- skin cancer
- Kaposi’s sarcoma
- cancers of the digestive tract
- lung cancer
- anal cancer
- breast cancer
- skin cancer
- non-Hodgkin’s lymphoma
- Kaposi’s sarcoma
- lung cancer
- liver cancer
The researchers noted that among HIV-negative women in France, breast cancer is the most common second cancer. Also, proportionally, more women than men injected street drugs in Dat’AIDS, so that is likely how they became exposed to HCV. Therefore, it should not be surprising that liver cancer, a consequence of HCV infection, was more common among women.
Bear in mind
Based on information in Dat’AIDS, the following is clear:
- 63% of participants were diagnosed with HIV prior to 1996 when ART became available
- 77% of participants had a CD4+ cell count below the 200-cell/mm3 mark at some point
Taken together, these two points suggest that some participants spent a period of time with profound immune deficiency and would have had uncontrolled production of HIV. It is possible that during this time their immune systems were too weak to recognize and eliminate persistent co-infections of cancer-causing viruses. What’s more, it is likely that during this period of profound immune deficiency, cancer-causing viruses could have transformed some infected cells into an abnormal state. In addition, emerging research suggests that some of HIV’s proteins can help transform abnormal cells into pre-cancer and cancer.
The present report from the Dat’AIDS study is important and shows that second new cancers are affecting almost 10% of people with HIV who survived their first cancer.
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, socio-economic 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 contain tips for better health in general and, in particular, 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 to learn about ways to reduce the risk of exposure to hepatitis C virus.
- Maintain a healthy weight.
- Engage in regular exercise.
- 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 one or more of the following additional interventions for discussion with a doctor or nurse:
- screening for HPV-related diseases and HPV vaccination
- screening for hepatitis B and C viruses, and, if necessary, treatment; a vaccine for HBV is available to prevent infection with this virus
- people with a history of smoking can find out about the availability of lung cancer screening
—Sean R. Hosein
Cancer – Government of Canada
Cancer – Government of Quebec
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