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Cancer risk among the HIV-infected elderly in the United States
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"Among HIV-infected men, 11.5% (95%CI = 9.6-13.3%) were diagnosed with cancer over 5 years, whereas 6.7% (95%CI = 4.7-8.6%) of HIV-infected women were diagnosed with cancer over 5 years (Fig. 1). The most frequent cancers among men were prostate cancer (5-year cumulative incidence = 2.7%), lung cancer (2.4%), NHL (0.9%), colorectal cancer (0.9%), and anal cancer (0.8%). Among women, the most frequent cancers were lung cancer (5-year cumulative incidence = 1.6%), colorectal cancer (1.0%), breast cancer (1.0%), NHL (0.4%), and pancreatic cancer (0.3%)."
"Regarding the question of 'when to begin HAART', risk for non-AIDS cancers are 2-fold higher (100% higher) when CD4s are below 700 and 3.7 fold higher when CD4 is 200-349 in the pre-HAART era in this study and also 2-fold higher for AIDS-defining risk when CD4s are <500 in the pre-HAART era (see tables 5a and 5d)."
Preventing Cancer in HIV+: keep CD4 >700 & viral load undetectable, start HAART Early, control inflammation
"Using a large cohort of HIV-positive veterans, we classified observation time by viral suppression status and calculated cancer risk compared with demographically similar uninfected veterans. Cancer risk was highest in the unsuppressed state, lower in early suppression, lower still in long-term suppression, and lowest in uninfected patients for all cancer, ADC, virus NADC, and several cancer types. Our findings suggest that early, sustained ART, which results in long-term viral suppression, may contribute to cancer prevention, with a marked risk reduction for ADC, a much more modest reduction for virus NADC, and possible reductions for certain types of nonvirus NADC. However, excess cancer risk remained among patients with long-term suppression. Future research should extend our sensitivity analyses to examine in more detail viral suppression thresholds less than 500 copies/mL, whether cancer risk continues to decrease with longer durations of long-term suppression, and the role of CD4+ cell count and CD4+-CD8+ cell count ratio......The benefits of ART include suppressed HIV viral load (as measured by plasma HIV RNA [21]), improved immune function (as measured by increasing CD4+ T-cell count), and reduced inflammation.....For all cancer, we saw a graded decrease in cancer risk from HIV-positive persons in the unsuppressed state to those with early suppression to those with long-term suppression. ......Of note, the RR remained elevated in persons with long-term suppression......."With a 100% risk reduction defined as reduction to the uninfected RR reference level of 1.00, long-term suppression was associated with a 94% reduction in excess ADC risk [(22.73 - 2.22)/(22.73 - 1.00)]; 65% of this reduction [(22.73 - 9.48)/(22.73 - 2.22)] occurred during early suppression. Patterns were similar for the 2 main ADCs, non-Hodgkin lymphoma and Kaposi sarcoma (Figure 2).
Association of Viral Suppression With Lower AIDS-Defining and Non-AIDS-Defining Cancer Incidence in HIV-Infected Veterans: A Prospective Cohort Study
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Cancer risk among the HIV-infected elderly in the United States
Yanik, Elizabeth L.; Katki, Hormuzd A.; Engels, Eric A.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
AIDS June 19 2016
Objective: HIV-infected people and elderly people have higher cancer risk, but the combined effects of aging and HIV are not well described. We aimed to evaluate the magnitude of cancer risk in the HIV-infected elderly population.
Design: We conducted a case-cohort study including a 5% sample of U.S. Medicare enrollees and all cancer cases aged at least 65 in linked cancer registries.
Methods: HIV was identified through Medicare claims. Among the HIV-infected, absolute cancer risk was calculated accounting for the competing risk of death. Associations between HIV and cancer were estimated with weighted Cox regression adjusting for demographic characteristics.
Results: Among 469 954 people in the 5% sample, 0.08% had an HIV diagnosis. Overall, 825 776 cancer cases were identified in cancer registries. Over 5 years, 10.1% of the HIV-infected elderly developed cancer, the most common diagnoses comprising lung (5-year cumulative incidence=2.2%), prostate (2.7%, among men), and colorectal cancer (0.9%), and non-Hodgkin lymphoma (0.8%). HIV was strongly associated with incidence of Kaposi sarcoma [adjusted hazard ratio (aHR)=94.4, 95% confidence interval (95%CI)=54.6-163], anal cancer (aHR=34.2, 95%CI=23.9-49.0) and Hodgkin lymphoma (aHR=6.3, 95%CI=2.8-14.3). HIV was also associated with incidence of liver cancer, non-Hodgkin lymphoma and lung cancer (aHR=3.4, 2.6, and 1.6, respectively).
Among HIV-infected men, 11.5% (95%CI = 9.6-13.3%) were diagnosed with cancer over 5 years, whereas 6.7% (95%CI = 4.7-8.6%) of HIV-infected women were diagnosed with cancer over 5 years (Fig. 1). The most frequent cancers among men were prostate cancer (5-year cumulative incidence = 2.7%), lung cancer (2.4%), NHL (0.9%), colorectal cancer (0.9%), and anal cancer (0.8%). Among women, the most frequent cancers were lung cancer (5-year cumulative incidence = 1.6%), colorectal cancer (1.0%), breast cancer (1.0%), NHL (0.4%), and pancreatic cancer (0.3%).
Cancer incidence was approximately 50% higher in HIV-infected compared with HIV-uninfected individuals (aHR = 1.52, 95%CI = 1.32-1.75; Table 1). HIV was most strongly associated with Kaposi sarcoma (aHR = 94.4, 95%CI = 54.6-163). HIV was also associated with elevated incidence of anal cancer (aHR = 34.2), Hodgkin lymphoma (aHR = 6.30), liver cancer (aHR = 3.35), NHL (aHR = 2.55), oral cavity/pharyngeal cancer (aHR = 1.79), and lung cancer (aHR = 1.61; Table 1). HIV was inversely associated with prostate cancer (aHR = 0.78, 95%CI = 0.63-0.98).
Conclusion: In the elderly, HIV infection is associated with higher risk for many cancers, although some associations were weaker than expected, perhaps reflecting effects of non-HIV pathways on cancer development. Due to the effects of HIV and aging, the HIV-infected elderly have a sizeable absolute risk, highlighting a need for cancer prevention.
Total cancer burden was high among the HIV-infected U.S. elderly, with one out of 10 people getting cancer over 5 years. This reflected an elevated risk for many HIV-associated cancers and a high frequency of cancers that are common among older adults but unassociated with HIV. The resulting cancer distribution reflects both HIV and aging effects. Overall, cancer risk was 50% higher in HIV-infected people than in HIV-uninfected people.
The most frequently diagnosed cancers were those associated with aging: lung, prostate, colorectal, and breast cancers, and NHL. Lung cancer and NHL risks are likely impacted by both HIV and age-related processes [13-16]. Lung cancer was the most common cancer, and it is a common cause of death in HIV-infected people [17,18]. These observations point to the potential importance of smoking cessation. Given the high incidence of lung cancer overall, current smokers in the elderly HIV population might particularly benefit from lung cancer screening with low-dose computed tomography [19].
In conclusion, the absolute risk of cancer in the U.S. HIV-infected elderly is sizeable, reflecting effects of both HIV and aging. HIV infection in the elderly is associated with higher risk for many cancers previously identified as HIV-associated. However, the relative elevation is lower for some of these cancers, likely due in part to contributions of HIV-unrelated causes of cancer in the elderly population. In fact, the most frequently identified cancers were those related to aging. These patterns highlight a clear need for cancer prevention in this age group and the importance of screening, particularly for lung, colorectal, and breast cancers, for which accepted screening modalities are available.
Introduction
HIV-infected individuals have elevated risk for a number of cancers [1,2]. In the general population, risk of most cancers increases with age, including cancers frequently diagnosed in HIV-infected people, for example non-Hodgkin lymphoma (NHL), lung cancer, and liver cancer [3]. Understanding the magnitude of cancer risk in the HIV-infected elderly can inform screening or prevention programs. As effective antiretroviral treatment has greatly prolonged life expectancy, the proportion of the HIV population in older age groups has increased and will likely continue increasing in the future. Because of these changes, obtaining robust data on cancer risk in the HIV-infected elderly is particularly important [4].
Because a small proportion of the current HIV population is older than 65 [5,6], examining the relationship between HIV and cancer in the elderly has been difficult. We used a linkage between data from cancer registries in the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute and Medicare claims (SEER-Medicare) to estimate absolute cancer risk among people aged 65 and older with an HIV diagnosis and evaluate the association between HIV and cancer in this age group [7].
Results
In the 5% subcohort, there were 469 954 people aged 65 years or older with Medicare during 2004-2011. In the subcohort, 41 604 people had a cancer diagnosis, which (as expected) comprised 5% of the 825 776 cancer cases among all Medicare enrollees aged 65 years or older both within and outside the subcohort. In total, our study population thus included 1 254 126 Medicare enrollees (469 954 in the subcohort, including 41 604 with cancer, plus 784 172 cancer cases outside the subcohort; Supplementary Figure). The most frequently diagnosed cancers were lung (N = 145 775), prostate (N = 142 940), breast (N = 93 919), and colorectal cancers (N = 93 555).
In the subcohort, 0.08% of people had an HIV diagnosis (N = 361). For these people, the median time between the start of follow-up and HIV diagnosis was 6 months (interquartile range = 3-23 months). Compared with people without an HIV diagnosis, HIV-infected individuals were more frequently male (73 vs. 42%) and of black race (36 vs. 9%).
HIV-infected people were younger at the start of follow-up (median of 66 vs. 70 years), but were more likely to die during follow-up (28 vs. 23%).
There were 653 cancer cases among HIV-infected people, including 55 AIDS-defining and 598 non-AIDS-defining cancers. Among HIV-infected individuals, 10.1% were diagnosed with cancer over the course of 5 years of follow-up [95% confidence interval (CI) = 8.7-11.5%, Fig. 1]. The most common cancer was lung cancer (5-year cumulative incidence = 2.2%), followed by prostate cancer (1.9%), colorectal cancer (0.9%), NHL (0.8%), and anal cancer (0.6%) (Fig. 1).
Among HIV-infected men, 11.5% (95%CI = 9.6-13.3%) were diagnosed with cancer over 5 years, whereas 6.7% (95%CI = 4.7-8.6%) of HIV-infected women were diagnosed with cancer over 5 years (Fig. 1). The most frequent cancers among men were prostate cancer (5-year cumulative incidence = 2.7%), lung cancer (2.4%), NHL (0.9%), colorectal cancer (0.9%), and anal cancer (0.8%). Among women, the most frequent cancers were lung cancer (5-year cumulative incidence = 1.6%), colorectal cancer (1.0%), breast cancer (1.0%), NHL (0.4%), and pancreatic cancer (0.3%).
Cancer incidence was approximately 50% higher in HIV-infected compared with HIV-uninfected individuals (aHR = 1.52, 95%CI = 1.32-1.75; Table 1). HIV was most strongly associated with Kaposi sarcoma (aHR = 94.4, 95%CI = 54.6-163). HIV was also associated with elevated incidence of anal cancer (aHR = 34.2), Hodgkin lymphoma (aHR = 6.30), liver cancer (aHR = 3.35), NHL (aHR = 2.55), oral cavity/pharyngeal cancer (aHR = 1.79), and lung cancer (aHR = 1.61; Table 1). HIV was inversely associated with prostate cancer (aHR = 0.78, 95%CI = 0.63-0.98).
Prostate cancer incidence of both localized/regional and distant stage cases appeared decreased among HIV-infected people, though the association was only significant for localized/regional prostate cancer (aHR = 0.74, 95%CI = 0.59-0.94; Table 1). HIV was not associated with breast cancer incidence at any stage. Incidence of localized and distant colorectal cancer was the same in individuals with and without HIV, whereas incidence of regional stage colorectal cancer was elevated among HIV-infected people (aHR = 1.70, 95%CI = 1.12-2.58).
Discussion
Total cancer burden was high among the HIV-infected U.S. elderly, with one out of 10 people getting cancer over 5 years. This reflected an elevated risk for many HIV-associated cancers and a high frequency of cancers that are common among older adults but unassociated with HIV. The resulting cancer distribution reflects both HIV and aging effects. Overall, cancer risk was 50% higher in HIV-infected people than in HIV-uninfected people.
The most frequently diagnosed cancers were those associated with aging: lung, prostate, colorectal, and breast cancers, and NHL. Lung cancer and NHL risks are likely impacted by both HIV and age-related processes [13-16]. Lung cancer was the most common cancer, and it is a common cause of death in HIV-infected people [17,18]. These observations point to the potential importance of smoking cessation. Given the high incidence of lung cancer overall, current smokers in the elderly HIV population might particularly benefit from lung cancer screening with low-dose computed tomography [19].
As in other studies, HIV was associated with higher incidence of many virus-related cancers, such as Kaposi sarcoma related to human herpesvirus-8, lymphomas related to Epstein-Barr virus, anal cancer related to human papillomavirus, and liver cancer related to hepatitis C and B viruses [1]. These associations provide further evidence that elevated cancer risk is at least partly because HIV-infected individuals have poor immunologic control of oncogenic viruses. However, some associations were weaker than those identified in younger people. In our study, Kaposi sarcoma incidence was about 100 times higher and NHL incidence was 2-3 times higher in HIV-infected people compared with HIV-uninfected people. By comparison, in studies of younger HIV-infected populations, Kaposi sarcoma incidence is 200-800 times higher and NHL incidence is 6-17 times higher than in the general population [6,20,21]. This lower relative increase could reflect more widespread HIV treatment, viral suppression, and immune reconstitution compared with younger HIV populations [21,22], which may result in better control of oncogenic viruses and, for Kaposi sarcoma, possible regression of tumors before they reach a clinically detectable stage [23]. Associations could also be weaker because of larger contributions of HIV-unrelated causal pathways in the elderly. For instance, our NHL associations were more similar to findings in younger HIV populations when evaluated by NHL subtype [20,24], but the HIV-associated subtypes (diffuse large B-cell lymphoma, Burkitt lymphoma, and central nervous system lymphoma) made up a smaller portion of the NHL burden in our population.
Even though they contributed substantially to the cancer burden in our HIV population, overall incidence of breast and colorectal cancer was not associated with HIV, and prostate cancer incidence appeared lower. Reduced risk was suggested for distant stage prostate cancer, arguing against a deficit of prostate cancer screening in HIV-infected men. As screening detects cancers early, reduced screening typically manifests as a reduced risk of only localized cancer, sometimes accompanied by an increase in regional/distant stage cancer. Importantly, prostate cancer screening through prostate-specific antigen testing is not generally recommended, due to a lack of survival benefit [19]. However, for breast and colorectal cancer, current recommendations support screening up to age 75 [19]. Because these cancers are common in the older HIV population, and risk was largely similar to risk observed in HIV-uninfected adults, our findings support adherence to these guidelines for HIV-infected people.
Our study has several strengths. Using an efficient case-cohort design, we were able to leverage the SEER-Medicare database to study a large, population-based sample of elderly HIV-infected adults and calculate absolute risk. This sample also provided a comparable HIV-uninfected population. Reliable cancer diagnoses were provided by SEER cancer registries, which apply rigorous data quality standards for case ascertainment.
Our study is limited by missing information. We did not have claims information for individuals before age 65, so we did not know how long individuals had been HIVdiagnosed. Medication claims were only available after 2006, when prescription benefits were introduced, and so we could not systematically assess antiretroviral use, which influences risk for HIV-associated cancers. We also lacked information on other cancer risk factors, such as tobacco use or human papillomavirus infection.
In conclusion, the absolute risk of cancer in the U.S. HIV-infected elderly is sizeable, reflecting effects of both HIV and aging. HIV infection in the elderly is associated with higher risk for many cancers previously identified as HIV-associated. However, the relative elevation is lower for some of these cancers, likely due in part to contributions of HIV-unrelated causes of cancer in the elderly population. In fact, the most frequently identified cancers were those related to aging. These patterns highlight a clear need for cancer prevention in this age group and the importance of screening, particularly for lung, colorectal, and breast cancers, for which accepted screening modalities are available.
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