People with HIV Are at Higher Risk for Several Types of Cancer, Large Study Finds

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People living with HIV remain at risk for AIDS-defining cancers in the era of effective antiretroviral therapy, and also have higher rates of several non-AIDS cancers than the general population, including lung, anal, and liver cancer, according to findings from a study of more than 86,000 HIV-positive people published in the October 6 Annals of Internal Medicine.

Since the advent of effective combination antiretroviral therapy (ART) in the mid-1990s, rates of the 3 AIDS-defining cancers -- Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer -- have fallen among people with HIV. These cancers are caused by opportunistic viruses that can take hold when the immune system is damaged and CD4 T-cells counts are low, though human papillomavirus (HPV) also causes cervical and anal cancer in otherwise healthy people.

Most studies, however, have found that HIV-positive people have a higher overall risk for other non-AIDS-related cancers compared to HIV-negative populations, although data have been inconsistent about specific cancer types. In fact, cancer rates among people with HIV have risen over time as they live long enough to develop malignancies.

Michael Silverberg from Kaiser Permanente Northern California and fellow investigators evaluated trends in cumulative incidence of common cancer types by HIV status among participants in the large North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).

This study included 86,620 people with HIV from 16 cohorts in the U.S. and Canada, as well as 196,987 HIV-negative adults from 5 cohorts selected to be similar in terms of age, sex, and race/ethnicity. Participants were followed between 1996 -- when effective ART started to become widely available -- and 2009.

About 85% of the HIV-positive NA-ACCORD participants were men, about 40% were white and 40% were black, and the median age was approximately 45 years. About 40% were men who have sex with men and about 20% had a history of injection drug use. Approximately 20% were coinfected with hepatitis C virus (HCV) while 4% also had hepatitis B virus (HBV). The proportion on ART increased from 39% during 1996-1999 to 74% during 2005-2009 and the median CD4 count rose from 309 to 382 cells/mm3.

The researchers looked at cumulative incidence (new cases) for 9 types of cancer by age 75, as well as calendar trends in cumulative incidence and hazard rates, according to HIV status and taking into account the competing risk of death due to other causes.

Results

o   Kaposi sarcoma: 4.4% vs 0.01%;

o   Non-Hodgkin lymphoma: 4.5% vs 0.7%.

o   Lung cancer: 3.4% vs 2.8%;

o   Anal cancer: 1.5% vs 0.05%;

o   Colorectal cancer: 1.0% vs 1.5%;

o   Liver cancer: 1.1% vs 0.4%;

o   Hodgkin lymphoma: 0.9% vs 0.09%;

o   Oral cavity or mouth and throat cancer: 0.8% vs 0.8%;

o   Melanoma: 0.5% vs 0.6%.

"In the era before antiretroviral therapy, people who were infected with HIV were dying of AIDS. Now that use of this therapy is greatly increasing the lifespan of HIV-infected patients, their risk of developing other diseases, such as cancer, has increased," Silverberg said in a Kaiser Permanente press release. "These patients have a higher burden of cancer compared with the general population due to impaired immune function and chronic inflammation, as well as a higher prevalence of risk factors including smoking and viral coinfections."

"Our approach allowed us to disentangle the effects of longevity from other factors on the risk of cancer," Silverberg explained. "For example, we found that longevity was the main contribution to the increased risk over time for anal, colorectal and liver cancers. The risk for other cancers, such as lung cancer, melanoma, and Hodgkin's lymphoma, did not appear to increase over time. This was because the increased risk with longevity was compensated for by other factors, such as decreases in smoking or adverse sun exposure behaviors."

The non-AIDS cancers in this study were a mix of those caused by viruses -- including anal cancer (HPV) and liver cancer (HBV and HCV) -- as well as those with no confirmed viral cause, such as melanoma and lung cancer. Many HIV/HCV coinfected people are reaching the age at which HCV-related hepatocellular carcinoma, a type of liver cancer, typically develops.

The reasons for increased risk of non-infectious cancers in HIV-positive people on ART is not fully understood, but residual immune system damage that does not reverse with treatment and chronic inflammation due to persistent low-level HIV infection may play a role.

"The high cumulative incidences by age 75 years for Kaposi sarcoma, non-Hodgkin lymphoma, and lung cancer support early and sustained antiretroviral therapy and smoking cessation," the study authors concluded.

In their discussion the researchers suggested that HIV-positive smokers may benefit from new guidelines for annual lung cancer screening with low-dose computed tomography, as well as targeted smoking cessation efforts. People with HIV may also need more frequent colorectal cancer screening.

Regarding the infectious cancers, they emphasized the importance of universal HBV vaccination, expanded HPV vaccination, and antiviral treatment for hepatitis B and hepatitis C -- the latter of which can now be cured using effective and well-tolerated interferon-free therapy. The increased anal cancer risk highlights the need for further research on the harms and benefits of anal dysplasia screening (e.g. Pap smears). Early and sustained antiretroviral treatment is the only known approach to prevent Kaposi sarcoma and non-Hodgkin's lymphoma, and it may also play a role in reducing other cancers linked to immunosuppression or inflammation.

10/6/15

Reference

MJ Silverberg, B Lau, CJ Achenbach, et al.Cumulative Incidence of Cancer Among Persons With HIV in North America: A Cohort Study. Annals of Internal Medicine 163(7):507-518. October 6, 2015.

Other Source

Kaiser Permanente. Study Estimates HIV-Infected Individuals Have Increased Cumulative Incidence of Lifetime Cancer Risk. Press release. October 5, 2015.