Hodgkin lymphoma and immunodeficiency in persons with HIV/AIDS

Abstract

In persons with HIV/AIDS (PWHAs), Hodgkin lymphoma (HL) risk is increased. However, HL incidence in PWHAs has unexpectedly increased since highly active antiretroviral therapy (HAART) was introduced. We linked nationwide HIV/AIDS and cancer registry data from 1980 through 2002. Immunity was assessed by CD4 T-lymphocyte counts at AIDS onset. Annual HL incidence rates were calculated for 4 through 27 months after AIDS onset. IntroductionHodgkin lymphoma (HL) risk is significantly increased in persons with HIV/AIDS (PWHAs) of all ages. [1][2][3][4][5][6][7][8][9][10][11] Risks relative to the general population are increased from 5-to 15-fold. Additionally, most HL cases in PWHAs are mixed cellularity (MC) and lymphocyte-depleted (LD) subtypes, whereas the nodular sclerosing (NS) subtype predominates in young adults without HIV/AIDS. 2,12,13 That HIV/AIDS-related immunosuppression would affect HL risk and subtype distribution is not surprising. Persons with genetic conditions associated with T-lymphocyte immune dysfunction have a higher risk of HL, and patients with HL may have underlying abnormalities of T-cell immunity. 14 Few studies of HL in PWHAs have had sufficient data to examine risks in the era of highly active antiretroviral therapy (HAART). By controlling HIV replication with combination therapies, HAART improves immune function, and its use is associated with reduced incidence of Kaposi sarcoma and non-Hodgkin lymphoma (NHL), the 2 most common AIDSassociated cancers. [15][16][17][18] Unexpectedly, however, HL risk in PWHAs increased after HAART became available in 1996. 15,18 Consistent with this temporal increase, HL incidence was reported to be higher in HIV-infected persons using HAART than in those not using it. 16 To address the role of immunity in HL etiology, we examined HL risk in a large multicenter study linking HIV/AIDS and cancer registry data. Since 1990, CD4 T-lymphocyte counts have been increasingly recorded by HIV/AIDS registries, permitting prospective studies of HL incidence using this marker of immune status to stratify subjects. We also examined the relationship between CD4 count and the incidence of specific HL subtypes provided by the cancer registries. Patients, materials, and methodsSince 1991, we have periodically linked HIV/AIDS and cancer registry data in the United States. The current linkage included the states of Connecticut, Georgia, Florida, Massachusetts, Michigan, and New Jersey, and the metropolitan areas of Los Angeles, San Diego, and San Francisco, CA; New York City, NY; and Seattle, WA. We included HIV/AIDS cases registered through 2002 and linked them to cancer diagnoses during periods when cancer registry data were considered complete. Details of the matching approach have been presented elsewhere. 6,9,11,19 Briefly, a probabilistic algorithm identified record linkages using the social security number, name, sex, race, and birth and death dates. Possible linkages were reviewed by authorized registry personnel to ensure their validity, and questionable linkages we...

Relationship between current level of immunodeficiency and non‐acquired immunodeficiency syndrome‐defining malignancies

“…Some studies support our results. 21,38 Biggar et al found that the incidence of HL is highest at moderate CD4 counts (150-199 cells/mm 3 ), 38 and another study 39 found that the risk of HL increased for CD4 counts of <350 cells/mm 3 and peaked at 50 to 99 cells/mm 3 . We found a linear relationship between with decreasing CD4 count and increasing incidence of HL.…”

Human immunodeficiency and Hodgkin lymphoma

“…Despite this being the second most common cancer in Africa incidence remains small when in contrast to the 5-25-fold risk observed in western populations [26], [27] and [28]. Even so, none of the other tumour types examined being oral, liver or stomach cancer, melanoma, leukaemias or sarcomas showed a similar increased risk [25].…”

“…Immune reconstitution with cART is causing an increased risk for these tumours by shifting HIV-infected individuals to a level of immunosuppression associated with highest risk [27] and [28]. The Reed Sternberg (RS) cell seems to play a central role in facilitating such complex interactions.…”

Spindle-shaped CD163+ rosetting macrophages replace CD4+ T-cells in HIV-related classical Hodgkin lymphoma

“…However, classical Hodgkin lymphoma is observed more frequently 1 and HIV patients have a 9.4-fold increased risk of developing classical Hodgkin lymphoma compared with the general population. 2,3 Although HIV-related classical Hodgkin lymphoma occurs at any CD4 blood count, it is most frequently observed in patients with a moderate immune deficiency and CD4 blood counts of 150-249 cells/ml. 2,4 As Hodgkin-and Reed-Sternberg cells, the tumor cells in classical Hodgkin lymphoma, usually constitute a small subpopulation of the cells in affected lymph nodes; it is likely that the microenvironment, largely composed of CD4 þ T regulatory 1 cells, has an essential role in the pathophysiology of the disease.…”

“…2,3 Although HIV-related classical Hodgkin lymphoma occurs at any CD4 blood count, it is most frequently observed in patients with a moderate immune deficiency and CD4 blood counts of 150-249 cells/ml. 2,4 As Hodgkin-and Reed-Sternberg cells, the tumor cells in classical Hodgkin lymphoma, usually constitute a small subpopulation of the cells in affected lymph nodes; it is likely that the microenvironment, largely composed of CD4 þ T regulatory 1 cells, has an essential role in the pathophysiology of the disease. 5 As HIV infection usually involves decreased CD4 þ T-cell counts in the peripheral blood, several studies have addressed the issue of the microenvironment in HIV-associated Hodgkin lymphoma and have found the CD4/CD8 T-cell ratio to be inverted.…”