A large study with follow-up over 14 years offers a unique way of looking at the risk of cancer among HIV-positive individuals by accounting for the competing risk of death in the era of highly effective antiretroviral therapy (ART), as reported on October 6 in the Annals of Internal Medicine. The study was funded primarily by grants from the National Institutes of Health.
The study population consisted of 86,620 HIV-infected and 196,987 uninfected adults followed between 1996 and 2009 in 16 cohorts from the U.S. and Canada participating in the NA-ACCORD.
Researchers used the competing risk of death approach to estimate cumulative cancer incidence by HIV status and calendar era. Among HIV-infected subjects, the median CD4 count increased. Despite increasing age, the mortality rate decreased, but even in 2005-2009 the mortality rate was over three-fold higher than in uninfected subjects.
“This analysis provides easily interpretable information for HIV patients and their providers about their long-term cancer risk, and helps us identify where public health and clinical efforts should be focused to achieve the biggest impacts,” said co-author Richard D. Moore, MD, MHS, of the Johns Hopkins School of Medicine, and overall principal investigator of the North American Cohort Collaboration on Research and Design (NA-ACCORD).
“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,” said lead author Michael J. Silverberg, PhD, MPH, Research Scientist at the Kaiser Permanente Northern California Division of Research. “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 co-infections.”
“Our approach allowed us to disentangle the effects of longevity from other factors on the risk of cancer,” explained Silverberg. “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 researchers identified several clinical implications regarding cancer screening in HIV patients:
— The high smoking prevalence in HIV patients, along with high lung cancer incidence, suggests that HIV-infected smokers may benefit from new guidelines for annual lung cancer screening with low-dose computed tomography. In addition, development of targeted smoking cessation interventions for HIV patients should remain a priority.
— The rise in colorectal cancer risk among HIV patients, despite a decline in the general population, indicates the possible need for increased screening among HIV patients aged 50-75 years, as recommended for the general population.
— The increasing risk of liver cancer over time indicates a need to ensure universal hepatitis B virus (HBV) vaccination for HIV patients who are HBV seronegative, and to provide treatment of HBV infection using antiretroviral therapy (ART) regimens with anti-HBV activity and of hepatitis C virus (HCV) infection with recently approved interferon-free therapies.
— The highly effective human papillomavirus (HPV) vaccine, which was licensed in 2011 for the prevention of anal cancer, has been found to produce immunity in HIV patients, suggesting that vaccination has the potential to substantially decrease the burden of anal and possibly HPV-related oral cavity/pharyngeal cancers, although further research is needed.
— Research is also needed to follow-up on observational studies that suggest statin use by HIV patients may reduce cancer risk, presumably due to their anti-inflammatory effects.
— Efforts need to be intensified to promote early, sustained ART, the only known approach to prevention of Kaposi sarcoma and non-Hodgkin’s lymphoma and possibly other cancers linked to immunosuppression or inflammation.
