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Deaths Attributable to Cancer in the US Human Immunodeficiency Virus Population During 2001-2015
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Clinical Infectious Diseases 25 July 2020 Marie-Josèphe Horner, Meredith S. Shiels, Ruth M. Pfeiffer, and Eric A. Engels
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
Cancer-attributable mortality rates increased steeply with age, reflecting the increasing incidence of many non-AIDS-defining cancers among older age groups. In the over-60 age group, we observed that 1 in 5 deaths was attributed to cancer. The distribution of deaths also shifted dramatically with advancing age, showing an increase in the proportion of deaths attributable to non-AIDS-defining cancers. Non-Hispanic whites had the highest PAF (17.1%), but non-Hispanic blacks had the highest rates of both overall and cancer-attributable mortality.
The composition of cancer-attributable deaths shifted such that the proportion of deaths attributable to non-AIDS-defining cancers increased from 7.2% during 2001-2005 to 11.8% during 2011-2015 (Figure 1A), while the proportion attributable to AIDS-defining cancers remained stable (approximately 5%). Among the leading non-AIDS-defining cancers, the PAF for liver, lung, and anal cancers each increased by 0.6%, 0.5%, and 0.5%, respectively, between 2001-2005 and 2011-2015 (Supplementary Table 3). In contrast, the corresponding cancer-attributable mortality rates declined across calendar periods for AIDS-defining and non-AIDS-defining cancer groups (Figure 1B).
Across demographic groups (Table 3), the PAF was higher among men (15.3%) than women (12.5%). The cancer-attributable mortality rate and PAF increased across age groups (Figure 1C, 1D). Among those aged ≥60 years, 19.0% of deaths were attributed to cancer compared with 11.4% among those aged 20-39 years, and the cancer-attributable mortality rate was 5-fold higher (952.2 vs 191.1 per 100 000 person-years). The composition of cancer-attributable deaths also shifted with age; the proportion of deaths attributable to non-AIDS-defining cancers increased from 3.3% among those aged 20-39 years to 16.4% among those aged ≥60 years, while the proportion attributable to AIDS-defining cancers declined (8.1% vs 2.3%; Figure 1C). The cancer-attributable mortality rate for non-AIDS-defining cancers increased with age from 27.0 per 100 000 person-years in those aged 20-49 years to 818.0 per 100 000 person-years in those aged ≥60 years, while the cancer-attributable mortality rate for AIDS-defining cancers remained stable (Figure 1D). Across calendar periods, all age groups experienced an increase in the PAF (Figure 2A) and substantial declines in the cancer-attributable mortality rate (Figure 2B). The most pronounced increase in the PAF occurred among those aged 40-59 years for whom the PAF increased from 12.7% during 2001-2005 to 17.0% during 2011-2015. Between 2001-2005 and 2011-2015, the cancer-attributable mortality rate declined by 55.6% among those aged 20-39 years and by 40.4%-41.0% among those aged 40-59 years and 60+ years.
Although cancer-attributable mortality has declined over time, it remains high and represents a growing fraction of deaths in the US HIV population. Mortality from non-AIDS-defining cancers may rise as the HIV population ages. ART access, early cancer detection, and improved cancer treatment are priorities for reducing cancer-attributable mortality.
The mortality patterns described here point to opportunities for public health interventions to reduce cancer mortality among PLWH. Early and sustained ART is important for primary prevention of KS and NHL. Improving uptake of HCV screening among all asymptomatic adults without known liver disease and HCV treatment are critical to reduce liver cancer incidence, and primary prevention of lung cancer and other cancers through smoking cessation is important [29, 30]. With the proportion of PLWH aged ≥65 years expected to increase to 21% by 2030, early cancer detection through screening and improved treatment access should be priorities [23]. PLWH have worse cancer survival than those not living with HIV partly due to advanced cancer stage at diagnosis [31-33]. Finally, disparities in cancer treatment among PLWH also contribute to poor survival [34].
In summary, our study provides new population-based estimates of cancer-attributable mortality for PLWH in the United States. Cancer-attributable mortality remains much higher in the HIV population than the general population, and the fraction of deaths due to cancer has been increasing over time. Although NHL and KS are among the leading causes of cancer deaths in the HIV population, the spectrum of cancer deaths is shifting toward non-AIDS-defining sites, and mortality due to non-AIDS-defining cancers will likely rise as the HIV population ages. The evolving pattern of cancer deaths in the HIV population underscores the continued importance of ART access, early cancer detection, and improved cancer treatment among PLWH.
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Deaths Attributable to Cancer in the US Human Immunodeficiency Virus Population During 2001-2015
Clinical Infectious Diseases 25 July 2020 Marie-Josèphe Horner, Meredith S. Shiels, Ruth M. Pfeiffer, and Eric A. Engels
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
Abstract
Background
Antiretroviral therapy (ART) has reduced mortality among people living with human immunodeficiency virus (HIV), but cancer remains an important cause of death. We characterized cancer-attributable mortality in the HIV population during 2001-2015.
Methods
We used data from population-based HIV and cancer registries in the United States (US). Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HRs) associating cancer diagnoses with overall mortality. Population-attributable fractions (PAFs) were calculated using these HRs and the proportion of deaths preceded by cancer. Cancer-specific PAFs and cancer-attributable mortality rates were calculated for demographic subgroups, AIDS-defining cancers (Kaposi sarcoma [KS], non-Hodgkin lymphoma [NHL], cervical cancer), and non-AIDS-defining cancers.
Results
Cancer-attributable mortality was 386.9 per 100 000 person-years, with 9.2% and 5.0% of deaths attributed to non-AIDS-defining and AIDS-defining cancers, respectively.
Leading cancer-attributable deaths were from NHL (3.5%), lung cancer (2.4%), KS (1.3%), liver cancer (1.1%), and anal cancer (0.6%).
Overall, cancer-attributable mortality declined from 484.0 per 100 000 person-years during 2001-2005 to 313.6 per 100 000 person-years during 2011-2015, while the PAF increased from 12.6% to 17.1%; the PAF for non-AIDS-defining cancers increased from 7.2% to 11.8% during 2011-2015.
Cancer-attributable mortality was highest among those aged ≥60 years (952.2 per 100 000 person-years), with 19.0% of deaths attributed to non-AIDS-defining cancers.
Conclusions
Although cancer-attributable mortality has declined over time, it remains high and represents a growing fraction of deaths in the US HIV population. Mortality from non-AIDS-defining cancers may rise as the HIV population ages. ART access, early cancer detection, and improved cancer treatment are priorities for reducing cancer-attributable mortality.
Among prevalent cancers, the median time between diagnosis and the start of follow-up was 0.8 years (IQR, 0.0-2.6 years; Supplementary Table 2). For all prevalent cancers combined, 95% had 0 to 4.59 years of survival time from their cancer diagnosis until entering the cohort, and only 5% had a survival time of 4.60 to 5 years (Supplementary Table 2).
There were 95 554 deaths during follow-up (mortality rate, 2671 per 100 000 person-years), and 17.5% of deaths were preceded by cancer (pd = 0.175). The adjusted HR for cancer and death was 5.79 (95% confidence interval [CI], 5.69-5.89), resulting in a PAF of 14.5% (95% CI, 13.6%-15.4%). The corresponding cancer-attributable mortality rate was 386.9 per 100 000 person-years (Table 2).
Non-AIDS-defining cancers collectively contributed a larger fraction of deaths than AIDS-defining cancers (PAFs, 9.2% vs 5.0%; cancer-attributable mortality rates, 245.7 vs 134.1 per 100 000 person-years; Table 2). Individual cancer sites that contributed the most deaths were NHL (3.5%), lung cancer (2.4%), KS (1.3%), liver cancer (1.1%), and anal cancer (0.6%).
As shown in Table 3, overall mortality among PLWH declined from 3839 per 100 000 person-years during 2001-2005 to 1835 per 100 000 person-years during 2011-2015. Between 2001-2005 and 2011-2015, the cancer-attributable mortality also declined from 484.0 to 313.6 per 100 000 person-years, while the PAF increased from 12.6% during 2001-2005 to 17.1% during 2011-2015 (Table 3). The composition of cancer-attributable deaths shifted such that the proportion of deaths attributable to non-AIDS-defining cancers increased from 7.2% during 2001-2005 to 11.8% during 2011-2015 (Figure 1A), while the proportion attributable to AIDS-defining cancers remained stable (approximately 5%). Among the leading non-AIDS-defining cancers, the PAF for liver, lung, and anal cancers each increased by 0.6%, 0.5%, and 0.5%, respectively, between 2001-2005 and 2011-2015 (Supplementary Table 3). In contrast, the corresponding cancer-attributable mortality rates declined across calendar periods for AIDS-defining and non-AIDS-defining cancer groups (Figure 1B).
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