Cancer Incidence Falling in Large U.S. Veterans HIV Cohort

Cancer incidence fell significantly from 1997-2000 to 2009-2012 in a 45,000-person analysis of HIV-positive members of the Veterans Aging Cohort Study (VACS). Cancer incidence in HIV-positive veterans compared with HIV-negative veterans also fell significantly over those years but remained significantly higher in the HIV group in 2009-2012, according to the study.

Cancer has emerged as a leading cause of morbidity and mortality in people with HIV infection. After the arrival of potent combination antiretroviral therapy (ART), incidence of AIDS cancers dropped while incidence of non-AIDS cancers rose. When cancer incidence calculations are adjusted for age and other demographic variables, non-AIDS cancer incidence has dropped, remained stable or increased in different populations. VACS researchers conducted a new study to chart changes in adjusted cancer incidence in veterans with versus without HIV infection during the combination ART area.

VACS, the largest HIV cohort in North America, enrolls HIV-positive veterans when they enter HIV care and matches each to two HIV-negative veterans by age, sex, race/ethnicity and clinical site. Researchers identified cancer diagnoses in VACS by linking the cohort to the Veterans Affairs Central Cancer Registry. They grouped cancers into AIDS-defining cancers (ADC), all non-AIDS-defining cancers (NADC), virus-related NADC and nonvirus-related NADC. The researchers divided cancer diagnoses into four periods: 1997-2000, 2001-2004, 2005-2008 and 2009-2012. They calculated age-, sex- and race/ethnicity-adjusted standardized incidence rates (IR) for all cancer groups and standardized incidence rate ratios (IRR) to compare incidence in veterans with versus without HIV.

For the years 1997-2012, the study group included 44,787 veterans with HIV and 96,852 matched veteran controls without HIV. Age averaged 48 years in the entire cohort. The HIV group and non-HIV group were largely male (98% and 97%) and mostly black (49% and 47%) or white (39% and 39%). Similar high proportions in the HIV group and the non-HIV group ever smoked (61% and 62%), and one-third in each group had a history of alcohol abuse or dependence.

Among veterans with HIV, 3519 veterans had 3714 incident cancers; among veterans without HIV, 5434 veterans had 5760 incident cancers. Crude cancer incidence increased significantly over the study period in veterans with HIV (P = .0019). But after adjustment for age, sex and race/ethnicity, overall cancer incidence fell significantly in HIV-positive veterans (P < .0001). Among veterans without HIV, crude cancer incidence increased significantly over the study period (P < .0001). After adjustment, cancer incidence did not change significantly in HIV-negative veterans (P = .074). IRR comparing cancer incidence in veterans with versus without HIV declined significantly over the study period (P < .0001) but remained significantly higher in HIV-positive veterans than HIV-negative veterans in the last period, 2009-2012 (IRR 1.6, 95% confidence interval [CI] 1.5 to 1.7).

Among HIV-positive veterans, ADC accounted for 31% of all cancers in 1997-2000 and for 11% in 2009-2012. ADC incidence dropped significantly in HIV-positive veterans over the study period (P < .0001). IRR comparing ADC incidence in veterans with versus without HIV fell significantly over the study period (P < .0001) but remained significantly higher in the HIV group in 2009-2012 (IRR 5.5, 95% CI 3.7 to 8.4).

In veterans with HIV, virus-related NADC accounted for 16% of cancers 1997-2000 and for 21% in 2009-2012. Incidence of virus-related NADC remained stable in HIV-positive veterans over the study period (P = .43) but rose significantly in veterans without HIV (P = .0082), largely because of increasing hepatocellular carcinoma incidence. IRR comparing virus-related NADC incidence in veterans with versus without HIV fell over the study period (P = .071) but remained significantly higher in HIV-positive veterans in 2009-2012 (IRR 3.5, 95% CI 2.7 to 4.5).

Nonvirus-related NADC accounted for 51% of cancers in HIV-positive veterans in 1997-2000 and for 68% in 2009-2012. Nonvirus-related NADC incidence fell significantly in HIV-positive veterans over the study period (P < .0001). IRR comparing nonvirus NADC incidence in veterans with versus without HIV fell significantly over the study period (P = .049) but remained significantly elevated in HIV-positive veterans in the latest study period (IRR 1.2, 95% CI 1.1 to 1.3). Lung cancer was the only nonvirus NADC for which incidence remained higher in HIV-positive veterans than HIV-negative veterans across all four study periods.

The VACS team points out that the rising crude cancer incidence in veterans with HIV indicates an increasing cancer burden in this group. But after adjustment for age, sex and race/ethnicity, incidence fell across the study period for all cancers (25% decline), ADC (55% decline), NADC (15% decline) and nonvirus-related NADC (20% decline). Yet overall cancer incidence rates remained 60% higher in veterans with than without HIV in the final study period, 2009-2012, mostly because of ADC, virus-related NADC and lung cancer (IRR 1.8).

The researchers propose that "improved HIV care most likely contributed to the declines [in cancer incidence among HIV-positive veterans], and we could anticipate that further adoption of early and sustained ART combined with ongoing ART regimen enhancements will produce additional declines in cancer incidence."

The VACS investigators note that these findings may not apply to women, who made up less than 5% of the study group.