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Cancer Risk in Older Persons Living With Human Immunodeficiency Virus Infection in the United States
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Clinical Infectious Diseases, Volume 67, Issue 1, 1 July 2018- Parag Mahale,1 Eric A. Engels,1 Anna E. Coghill,1 Amy R. Kahn,2 and Meredith S. Shiels1
1Division of Cancer Epidemiology & Genetics, National Cancer Institute, Rockville, Maryland, and 2New York State Cancer Registry, New York State Department of Health, Albany
Background
Cancer risk is increased in persons living with human immunodeficiency virus (HIV) (PLWH). Improved survival has led to an aging of PLWH. We evaluated the cancer risk in older PLWH (age ≥50 years).
Methods
We included data from the HIV/AIDS Cancer Match Study (1996-2012) and evaluated risks of Kaposi sarcoma (KS), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, and cervical, anal, lung, liver, oral cavity/pharyngeal, breast, prostate, and colon cancers in older PLWH with risk in the general population by calculating standardized incidence ratios (SIRs) and excess absolute risks (EARs). Cancer risk by time since HIV diagnosis was estimated using Poisson regression.
Results
We identified 10371 cancers among 183542 older PLWH. Risk was significantly increased for KS (SIR, 103.34), NHL (3.05), Hodgkin lymphoma (7.61), and cervical (2.02), anal (14.00), lung (1.71), liver (2.91), and oral cavity/pharyngeal (1.66) cancers, and reduced for breast (0.61), prostate (0.47), and colon (0.63) cancers. SIRs declined with age for all cancers; however, EARs increased with age for anal, lung, liver, and oral cavity/pharyngeal cancers. Cancer risk was highest for most cancers within 5 years after HIV diagnosis; risk decreased with increasing time since HIV diagnosis for KS, NHL, lung cancer, and Hodgkin lymphoma.
Conclusions
Cancer risk is elevated among older PLWH. Although SIRs decrease with age, EARs are higher for some cancers, reflecting a greater absolute excess in cancer incidence among older PLWH. High risk in the first 5 years after HIV diagnosis for some cancers highlights the need for early HIV diagnosis and rapid treatment initiation.
excess absolute risks (EARs)......
We identified 10371 cancers among 183542 older PLWH. Risk was significantly increased for KS (SIR, 103.34), NHL (3.05), Hodgkin lymphoma (7.61), and cervical (2.02), anal (14.00), lung (1.71), liver (2.91), and oral cavity/pharyngeal (1.66) cancers, and reduced for breast (0.61), prostate (0.47), and colon (0.63) cancers. SIRs declined with age for all cancers; however, EARs increased with age for anal, lung, liver, and oral cavity/pharyngeal cancers. Cancer risk was highest for most cancers within 5 years after HIV diagnosis; risk decreased with increasing time since HIV diagnosis for KS, NHL, lung cancer, and Hodgkin lymphoma
In our analyses that included >180000 older PLWH, we observed that cancer risk was elevated in older PLWH compared with the general population, although the relative risk for most cancers declined with age. However, EARs, which measure absolute risk and thus reflect the number of excess cancers occurring among PLWH, increased with age for some NADCs. Given the aging of PLWH and the increase in the burden of NADCs, it is essential to target available cancer prevention and screening strategies toward this population. Cancer prevention among PLWH is largely based on restoring immunity with HAART and reducing established cancer risk factors [36]. Timely linkage of care with HAART initiation and uninterrupted treatment for persons in whom HIV infection has been newly diagnosed is essential to restore immunity. This also gives an opportunity for healthcare providers to diagnose and treat coinfections and to initiate counseling on modification of lifestyle behaviors, such as smoking. General population screening guidelines for breast, prostate, and colon cancers should be followed. Cervical cancer screening is recommended at more frequent intervals than for HIV-uninfected women [37, 38], and the benefits of anal cancer screening are still being evaluated [37, 38]. Finally, screening for lung cancers with low-dose computed tomography may be beneficial, but more data are needed among PLWH [37, 38].....there is a continued need for cancer prevention and early detection among older PLWH. Cancer risk was also highest within the first 5 years after HIV diagnosis for most cancers, underscoring the importance of early HIV diagnosis, rapid initiation of HAART after HIV diagnosis, and interventions to reduce known risk factors in older PLWH.
A comparison of SIRs and EARs by age for evaluated cancers is depicted in Figure 1. The SIRs were the highest for the youngest age group (<50 years) for all cancers and decreased with age, except for Hodgkin lymphoma, for which the SIRs were largely constant. The EARs also decreased with age for KS, NHL, cervical cancer, and Hodgkin lymphoma. In contrast, the EARs increased with age for cancers of the anus, lung, liver, and oral cavity/pharynx.
Examining cancer incidence rates among PLWH by age group (Table 3), we observed a significant decrease in KS risk with increasing age. Compared with 50-59-year-olds, PLWH aged 60-69 (aIRR, 0.68) or ≥70 ( 0.43) years had lower KS rates (Ptrend = .001). In contrast, rates for lung, prostate, and colon cancers increased with age (Ptrend < .001) while the increasing trend for breast cancer was borderline significant (Ptrend = .058). Liver and oral cavity/pharyngeal cancer rates were higher among 60-69-year-olds than in the 50-59-year age group (Ptrend < .05). No association between age and cancer risk was observed for NHL (total or subtypes), cervical cancer, anal cancer, or Hodgkin lymphoma (Ptrend > .05).
PLWH with a prior AIDS diagnosis had increased rates of KS, NHL (particularly diffuse large B-cell lymphoma [aIRR, 1.97] and CNS lymphomas [5.17]), anal, lung, and oral cavity/pharyngeal cancer, and Hodgkin lymphoma than those without a previous AIDS diagnosis (aIRRs range, 1.37-2.66; Table 3). Prostate cancer rates were lower among those with a prior AIDS diagnosis (aIRR, 0.84), but rates of cervical, liver, breast, and colon cancer did not differ significantly.
The risk of most cancers was highest within the first 5 years after HIV diagnosis, gradually decreasing over time (Table 4). Significant decreasing trends were observed for KS (Ptrend < .001), total NHL (Ptrend < .001), lung cancer (Ptrend < .001), breast cancer (Ptrend = .02), and Hodgkin lymphoma (Ptrend = .04), with a marginally significant trend for prostate cancer (Ptrend = .07). In contrast, there was an indication that risk increased with increasing time since HIV diagnosis for anal (Ptrend = .07) and liver (Ptrend = .08) cancers. Excluding the first year after HIV diagnosis did not affect our results (Supplementary Table S3). Restricting the analyses to calendar years 2001-2012 did not affect the associations between age or time since HIV diagnosis and cancer risk (Supplementary Tables S5 and S6).
The associations between age and cancer risk did not differ by time since HIV diagnosis for all cancers (all Pinteraction > .05). However, there was significant heterogeneity in the association between time since HIV diagnosis and cancer risk by age for NHL (Pinteraction = .003) and Hodgkin lymphoma (Pinteraction = .02). The aIRRs for NHL decreased with time since HIV diagnosis for both age categories (Ptrend < .001 for ages 50-59 and ≥60 years). For Hodgkin lymphoma, the trend for decreasing rates with time since HIV diagnosis was observed only for ≥60-year-olds (Ptrend = .006) and not among those aged 50-59 years (Ptrend = .41).
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