Epidemiology of Nonkeratinocytic Skin Cancers Among Persons With AIDS in the United States

Emilie Lanoy; Graca M Dores; Margaret M Madeleine; Jorge R Toro; Joseph F Fraumeni, Jr; Eric A Engels

Disclosures

AIDS. 2009;23(3):385-393. 

In This Article

Abstract and Introduction

Abstract

Objective: Immunosuppression may increase risk for some skin cancers. We evaluated skin cancer epidemiology among persons with AIDS.
Design: We linked data from population-based US AIDS and cancer registries to evaluate risk of nonkeratinocytic skin cancers (melanoma, Merkel cell carcinoma, and appendageal carcinomas, including sebaceous carcinoma) in 497 142 persons with AIDS.
Methods: Standardized incidence ratios (SIRs) were calculated to relate skin cancer risk to that in the general population. We used logistic regression to compare risk according to demographic factors, CD4 cell count, and a geographic index of ultraviolet radiation exposure.
Results: From 60 months before to 60 months after AIDS onset, persons with AIDS had elevated risks of melanoma (SIR = 1.3, 95% confidence interval 1.1-1.4, n = 292 cases) and, more strongly, of Merkel cell carcinoma (SIR = 11, 95% confidence interval 6.3-17, n = 17) and sebaceous carcinoma (SIR = 8.1, 95% confidence interval 3.2-17, n = 7). Risk for appendageal carcinomas increased with progressive time relative to AIDS onset (P trend = 0.03). Risk of these skin cancers was higher in non-Hispanic whites than other racial/ethnic groups, and melanoma risk was highest among men who have sex with men. Melanoma risk was unrelated to CD4 cell count at AIDS onset (P = 0.32). Risks for melanoma and appendageal carcinomas rose with increasing ultraviolet radiation exposure (P trend <10-4 and P trend = 10-3, respectively).
Conclusion: Among persons with AIDS, there is a modest excess risk of melanoma, which is not strongly related to immunosuppression and may relate to ultraviolet radiation exposure. In contrast, the greatly increased risks for Merkel cell and sebaceous carcinoma suggest an etiologic role for immunosuppression.

Introduction

Persons immunosuppressed due to HIV infection are at increased risk for cancer, most notably for virus-related cancers such as Kaposi sarcoma (due to human herpesvirus 8), non-Hodgkin lymphoma (NHL, due to Epstein-Barr virus), and anogenital carcinomas [due to human papillomavirus (HPV)].[1,2] A similar spectrum of cancer risk is observed among solid organ transplant recipients, who receive immunosuppressive medications to prevent graft rejection.[3] Solid organ transplant recipients also have an elevated risk for both melanoma and, to a greater extent, squamous and basal cell carcinomas (two skin cancers derived from keratinocytes),[3,4,5] suggesting a role of immunologic mechanisms. Among transplant recipients, squamous cell skin cancers frequently present as highly invasive tumors and are associated with substantial morbidity.[6] Aggressive squamous cell skin cancers have also been described in HIV-infected persons.[7,8]

Reasons for the elevated risk of skin cancer in immunosuppressed individuals are not well established. In general, chronic exposure to ultraviolet solar radiation is the major risk factor for various types of skin cancer, which are most common in non-Hispanic whites, who have less protective skin pigment than non-Hispanic blacks and Hispanics.[9,10] Among transplant recipients, exposure to ultraviolet radiation is a risk factor for squamous cell skin cancer.[5,11] Ultraviolet radiation induces mutations in DNA in normal skin cells and, in addition, may have a local immunosuppressing effect in the skin.[12] Recent studies[13,14,15] suggest that some squamous cell skin cancers, especially in transplant recipients, may be caused by HPV.

Additional rare types of skin cancers have also been described to arise more frequently in transplant recipients and HIV-infected individuals than in the general population. Merkel cell carcinoma, which like melanoma appears to be derived from neural crest progenitor cells, occurs at increased incidence in these populations.[16,17] Of interest, a recent report described detection of a novel polyomavirus in Merkel cell carcinoma tumors,[18] suggesting that this cancer may be caused by a virus. In addition, based on several reported case series,[4,6,19] transplant recipients appear to be at increased risk for appendageal carcinomas, a group of related tumors showing differentiation toward one or more of the adnexal structures of the skin. Sebaceous carcinoma, a subtype of appendageal carcinoma, often arises on the face, especially the eyelids, and an excess risk has been suggested in transplant recipients and HIV-infected individuals.[19,20,21,22,23] This tumor type also occurs in conjunction with visceral malignancies, especially colon cancer, as part of Muir-Torre syndrome.[22,24,25,26,27]

In the present study, we utilized linked registry data to quantify the risk of various types of skin cancer in HIV-infected persons with AIDS. Our study examines HIV-related immunosuppression and ultraviolet radiation exposure as factors of potential etiologic importance for these cancers. Cancer registries in the United States do not collect information on the occurrence of the two most common types of skin cancer, squamous cell and basal cell skin cancers, so these outcomes could not be included. The present study also does not include the AIDS-defining cancers, Kaposi sarcoma and NHL, which can involve the skin, because these have been thoroughly evaluated in other studies of the HIV/AIDS population. Thus, our study focuses on the occurrence of melanoma, Merkel cell carcinoma, and appendageal carcinomas among persons with AIDS.

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