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. 2012 Oct 1;118(19):4869-76.
doi: 10.1002/cncr.27454. Epub 2012 Feb 22.

Increased Risk of Histologically Defined Cancer Subtypes in Human Immunodeficiency Virus-Infected Individuals: Clues for Possible Immunosuppression-Related or Infectious Etiology

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Increased Risk of Histologically Defined Cancer Subtypes in Human Immunodeficiency Virus-Infected Individuals: Clues for Possible Immunosuppression-Related or Infectious Etiology

Meredith S Shiels et al. Cancer. .
Free PMC article

Abstract

Background: Malignancies that occur in excess among human immunodeficiency virus (HIV)-infected individuals may be caused by immunosuppression or infections. Because histologically defined cancer subtypes have not been systematically evaluated, their risk was assessed among people with acquired immunodeficiency syndrome (AIDS).

Methods: Analyses included 569,268 people with AIDS from the HIV/AIDS Cancer Match Study, a linkage of 15 US population-based HIV/AIDS and cancer registries during 1980 to 2007. Standardized incidence ratios (SIRs) were estimated to compare cancer risk in people with AIDS to the general population overall, and stratified by age, calendar period (a proxy of changing HIV therapies), and time since onset of AIDS (a proxy of immunosuppression).

Results: Sixteen individual cancer histologies or histology groupings manifested significantly elevated SIRs. Risks were most elevated for adult T cell leukemia/lymphoma (SIR = 11.3), neoplasms of histiocytes and accessory lymphoid cells (SIR = 10.7), giant cell carcinoma (SIR = 7.51), and leukemia not otherwise specified (SIR = 6.69). SIRs ranged from 1.4 to 4.6 for spindle cell carcinoma, bronchioloalveolar adenocarcinoma, adnexal and skin appendage neoplasms, sarcoma not otherwise specified, spindle cell sarcoma, leiomyosarcoma, mesothelioma, germ cell tumors, plasma cell tumors, immunoproliferative diseases, acute lymphocytic leukemia, and myeloid leukemias. For several of these cancer subtypes, significant declines in SIRs were observed across calendar periods (consistent with decreasing risk with improved HIV therapies) or increase in SIRs with time since onset of AIDS (ie, prolonged immunosuppression).

Conclusions: The elevated risk of certain cancer subtypes in people with AIDS may point to an etiologic role of immunosuppression or infection. Future studies are needed to further investigate these associations and evaluate candidate infectious agents.

Figures

Figure 1
Figure 1
Standardized incidence ratios (SIRs) comparing risk of cancer in people with AIDS to the general population by calendar period. Points indicate SIRs and vertical lines indicate 95% confidence intervals. P-trend values are as follows: bronchioloalveolar adenocarcinoma (p-trend=0.02), sarcoma NOS (p-trend=0.0003), plasma cell tumors (p-trend=0.0001), neoplasms of histiocytes and accessory lymphoid cells (p-trend=0.05), leukemia NOS (p-trend=0.02) and adult T-cell leukemia/lymphoma (p-trend=0.01). Zero cases of adult T-cell leukemia/lymphoma occurred in people with AIDS during 1980–1989.
Figure 2
Figure 2
Standardized incidence ratios (SIRs) comparing risk of cancer in people with AIDS to the general population by time relative to AIDS onset. Points indicate SIRs and vertical lines indicate 95% confidence intervals. P-trend values are as follows: spindle cell sarcoma (p-trend=0.03), leiomyosarcoma (p-trend=0.006) and plasma cell tumors (p-trend=0.003). Zero cases of spindle cell sarcoma occurred in the period 60 months to 25 months before AIDS and the period 24 to 7 months before AIDS. The period 6 months before to 3 months after AIDS onset was excluded from the trend test, because increased medical surveillance at the time of AIDS diagnosis inflates cancer risk estimates during this time period.

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