New Cancer Rates Climbing With Age in HIV Patients, but Age Impact Differs by Cancer Type

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.

How the Study Worked

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.

What the Study Found

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).

Factors Linked to Higher Incidence of Infection-Related Cancer
Factors Linked to Higher Incidence of Infection-Related Cancer 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).
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.

Factors Linked to Higher Incidence of Infection-Unrelated Cancer
Factors Linked to Higher Incidence of Infection-Unrelated Cancer 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).
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.

Five-Year Forecast for Incidence of Infection-Related and Infection-Unrelated Cancer
Five-Year Forecast for Incidence of Infection-Related and Infection-Unrelated Cancer 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).
Teresa B. Southwell

What the Results Mean for You

This large many-year study made several important findings about cancer risk in people with HIV, including these key results:

  • Age 50 or older was linked to a higher incidence (new cancer detection rate) of both infection-related cancers and infection-unrelated cancers.
  • The impact of being 50 or older was greater for infection-unrelated cancers (7.3-folder higher incidence) than for infection-related cancers (1.6-fold higher incidence).
  • Incidence of infection-related cancer was 1.17-fold higher for every additional 10 years of age, while incidence of infection-unrelated cancer was 2.07-fold higher for every 10 years of age.
  • Incidence of infection-related cancer is expected to fall from 3.1 cases per 1000 people to 2.1 per 1000 over 5 years.
  • Incidence of infection-unrelated cancer is expected to rise from 4.1 cases per 1000 people to 5.9 per 1000 over 5 years.
  • Incidence of infection-unrelated cancer is expected to fall from 1.7 cases per 1000 people to 0.8 per 1000 people over 5 years in people who never smoked.

Infection-unrelated cancers include lung cancer, prostate cancer, cancer of the colon and rectum, and breast cancer. The researchers believe the rate of infection-unrelated cancer will rise for several reasons: (1) The HIV population is aging and these cancers become more frequent with older age. (2) Smoking causes two major infection-unrelated cancers -- lung cancer and cancer of the colon and rectum -- and a high proportion of people with HIV continue to smoke. (3) Low CD4 count and high viral load add to the risk of infection-related cancers. Because fewer people with HIV have untreated and advanced HIV infection, the rate of infection-related cancers is going down, so infection-unrelated cancers become more prominent.

Because of the projected surge in infection-unrelated cancers in people with HIV, the EuroSIDA researchers believe more attention should be paid to preventing these cancers and to studying the potential benefits of testing for these cancers. Regular testing for three infection-unrelated cancers -- prostate cancer, colorectal cancer, and breast cancer -- has become routine for many people, especially as they age. High rates of these cancers in people with HIV should encourage anyone with HIV to talk to their provider about current guidelines on testing for these cancers.

The leading infection-unrelated cancer in this EuroSIDA group, and in many HIV populations, is lung cancer. Avoiding smoking -- or quitting if you already smoke -- can help prevent not only lung cancer but mouth and throat cancer, colorectal cancer, liver cancer, other cancers, and other major diseases like heart disease and stroke. Quitting smoking isn't easy, but the United States has more people who quit smoking than who continue to smoke.2 Your HIV provider can help you quit by prescribing certain drugs or nicotine replacement therapy and by guiding you to effective smoke-ending strategies like the internet-based Positively Smoke Free, created especially for people with HIV (see link at reference 3).

Drinking too much alcohol can lead to cancer of the head and neck, esophagus, liver, breast, colon, and rectum.4 If you drink too much, talk to your HIV provider or case worker about finding ways to limit or stop drinking.

Some infection-related cancers can be prevented by using condoms to prevent transmission of cancer-causing viruses (HBV, HCV, HPV) and by getting vaccinated against HBV and HPV. Everyone with HIV who does not already carry hepatitis B virus (HBV) should get the HBV vaccine. The CDC recommends the HPV vaccine for women up to age 26, for gay or bisexual men with or without HIV up to age 26, and for other men up to age 21.5

References

  1. Shepherd L, Borges A Ledergerber B, et al. Infection-related and -unrelated malignancies, HIV and the aging population. HIV Med. 2016;17:590-600.
  2. The Health Consequences of Smoking -- 50 Years of Progress: A Report of the Surgeon General. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014.
  3. Positively Smoke Free. Created by experts, refined by real users like you.
  4. National Cancer Institute. Alcohol and cancer risk.
  5. Centers for Disease Control and Prevention. Human papillomavirus (HPV): Questions and answers. 2015.