May 5, 2017
Development of new cancers rose with older age in a 15,000-person analysis of HIV-positive people across Europe.1 Overall incidence (the new cancer detection rate) of infection-related cancers is forecast to drop as rates of untreated HIV infection continue to fall. But overall incidence of cancers not related to infection is forecast to rise, partly because of high rates of smoking and lung cancer in people with HIV.
Compared with the general population, people with HIV run a higher risk of many cancers. The reasons for this higher cancer risk with HIV are not fully understood. Reasons probably include high rates of cancer risk factors like smoking in people with HIV, more frequent infection with viruses that lead to cancers, and a weakened immune system because of HIV infection. Also, when people began living longer with HIV infection thanks to antiretroviral therapy, they began facing a higher risk of cancers that become more common in older age.
To learn more about cancer rates and risk in people with HIV, researchers conducted this large European study. They aimed to assess the impact of aging on two main types of cancer in people with HIV: infection-related cancer and infection-unrelated cancer.
The cancer analysis involved members of the EuroSIDA group, an ongoing study of HIV-positive people in 35 European countries, Israel, and Argentina. Twice a year, researchers collect information on EuroSIDA members and send it to a central database, where it can be analyzed later. Such information includes age, sex, CD4 count, viral load, antiretroviral therapy, and newly detected diseases including cancers.
The new cancer study focused on EuroSIDA members who had data recorded after January 1, 2001. Researchers analyzed their data until their last EuroSIDA study visit or death. The main goal was to see what new cancers developed in that time. The research team sorted cancers into two groups: Infection-related cancers include Kaposi sarcoma, Hodgkin lymphoma, non-Hodgkin lymphoma, cervical cancer, cancers of the anus, penis, vulva, vagina, liver, or stomach, and certain head and neck cancers. Infection-unrelated cancers include all other cancers, such as lung cancer and prostate cancer.
The researchers used standard statistical methods to estimate the impact of age on new development of infection-related cancers and infection-unrelated cancers. The method used also accounts for the potential impact of many other factors that can affect cancer risk, such as gender, smoking, CD4 count, viral load, and previous diagnoses of AIDS, cancers, and serious diseases like heart disease, kidney disease, and liver disease. Thus this method can estimate the impact of age alone on new cancers, regardless of whatever other risk factors a person has.
The study included 15,648 HIV-positive people with data available over a median of 6 years. When people entered the study, 16% were 50 or older and about one third smoked. Most study participants (88%) were white and most (73%) were men. At study entry, 15% of participants had a CD4 count at or below 200, and 55% had a viral load at or below 400 copies.
During the study period, 643 cancers developed in 610 people, including 388 infection-related cancers (60%) and 255 infection-unrelated cancers (40%). The most frequent infection-related cancers were non-Hodgkin lymphoma (116 cases), anal cancer (83 cases), and Kaposi sarcoma (62 cases). The most frequent infection-unrelated cancers were lung cancer (55 cases), prostate cancer (28 cases), and colorectal cancer (23 cases). People with infection-related cancer were older than those with infection-unrelated cancer when the cancer was detected (median 54 versus 46 years). And at cancer detection, people with infection-related cancer had a higher CD4 count (median 466 versus 342).
The analysis that accounts for many cancer risk factors at the same time figured that people 50 or older had a 62% higher incidence (new detection rate) or infection-related cancer than people 36 to 40 years old (Figure 1). Infection-related cancer incidence was 17% higher for every additional 10 years of age. Three HIV-related factors were strongly linked to infection-related cancer incidence: a current viral load above 400 copies meant an almost doubled cancer incidence, a current CD4 count below 200 (versus 500 or higher) was linked to almost a 4-fold higher incidence, and a current CD4 count between 200 and 349 (versus 500 or higher) was linked to almost a doubled incidence (Figure 1).
Figure 1. In a study of 15,648 people with HIV, factors linked to a higher incidence (new detection rate) of infection-related cancers included (1) being 50 or older (versus 36 to 40), (2) a current CD4 count below 200 (versus 500 or higher), (3) a current CD4 count of 200 to 349 (versus 500 or higher), and (4) HIV viral load above 400 copies (versus below). (Credit: Teresa B. Southwell)
For infection-unrelated cancers, being 50 or older (versus 36 to 40) was linked to a 7.3-fold higher cancer incidence and being 41 to 50 (versus 36 to 40) was linked to a 2.4-fold higher incidence (Figure 2). Incidence of infection-unrelated cancers doubled with every additional 10 years of age. Current CD4 count below 200 (versus 500 or higher) was linked to a 1.5-fold higher incidence of infection-unrelated cancer (Figure 2). Current smoking was linked to a doubled incidence of infection-unrelated cancer (Figure 2). The link between sub-200 CD4 count and higher infection-unrelated cancer incidence held true in people younger than 50 but not in those 50 or older. In contrast, the link between current smoking and higher infection-unrelated cancer incidence held true in people 50 or older but not in those younger than 50.
Figure 2. In a 6-year study of Europeans with HIV, factors linked to higher incidence of infection-unrelated cancers (like lung cancer and prostate cancer) included (1) age 41 to 50 (versus 36 to 40), (2) age 50 or older (versus 36 to 40), (3) current smoking, and (4) current CD4 count below 200 (versus 500 or higher). (Credit: Teresa B. Southwell)
Finally, the EuroSIDA researchers focused on 6111 people who entered the study before January 2001. During the study period, 243 infection-related cancers and 161 infection-unrelated cancers developed in this group. Assuming that current new-cancer trends continue, the researchers predicted how cancer incidence would change over the course of 5 years.
They figured that incidence of infection-related cancers will fall from 3.1 cases per 1000 people in 2011 to 2.2 per 1000 after 5 years (Figure 3). In contrast, they projected that incidence of infection-unrelated cancer would rise from 4.1 cases per 1000 in 2011 to 5.9 per 1000 after 5 years. There was one exception to this second forecast: Among people who never smoked, the researchers figured that incidence of infection-unrelated cancers would drop from 1.7 cases per 1000 in 2011 to 0.8 per 1000 after 5 years.
Figure 3. Cancer trends in 6111 people with HIV allowed researchers to project 5-year changes in incidence (new detection) of infection-related cancer (down from 3.1 to 2.2 per 1000 person-years), infection-unrelated cancer (up from 4.1 to 5.9 per 1000 person-years), and infection-unrelated cancer in people who never smoked (down from 1.7 to 0.8 per 1000 person-years). (Credit: Teresa B. Southwell)
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