title: Increased risk of histologically defined cancer subtypes in human immunodeficiency virus-infected individuals: clues for possible immunosuppression-related or infectious etiology.
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.
authors.affiliation: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA. shielsms@mail.nih.gov
authors.forename: Meredith S
authors.initials: MS
authors.lastname: Shiels
authors.forename: Eric A
authors.initials: EA
authors.lastname: Engels
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000150:complications* / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D016867:Immunocompromised Host; D015994:Incidence; D008297:Male; D008498:Medical Record Linkage; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000276:immunology* / Q000473:pathology / Q000821:virology; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors