Article

Lanoy E, Dores GM, Madeleine MM et al.Epidemiology of nonkeratinocytic skin cancers among persons with AIDS in the United States. AIDS 23:385-393

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20892, USA.
AIDS (London, England) (Impact Factor: 5.55). 01/2009; 23(3). DOI: 10.1097/QAD.0b013e3283213046
Source: DOAJ

ABSTRACT

Immunosuppression may increase risk for some skin cancers. We evaluated skin cancer epidemiology among persons with AIDS.
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.
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.
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 and P trend = 10, respectively).
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.

Download full-text

Full-text

Available from: Margaret M Madeleine
  • Source
    • "Six patients were excluded from the analyses due to loss of follow-up (n = 5) or change in ART to another class (protease inhibitors, n = 1). Twenty-six patients completed the 9 months of treatment, 8 with NNRTI (7 on EFV and 1 on nevirapine), 10 with MVC and 8 with MVC+RAL (Figpredict mortality[38,39]. We first analyzed variations of CD4 + T-cell counts and CD4/CD8 ratio in blood (see Fig 2A and 2B and S1 Table), and no differences were detected between groups. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Whether initiation of antiretroviral therapy (ART) regimens aimed at achieving greater concentrations within gut associated lymphoid tissue (GALT) impacts the level of mucosal immune reconstitution, inflammatory markers and the viral reservoir remains unknown. We included 12 HIV- controls and 32 ART-naïve HIV patients who were randomized to efavirenz, maraviroc or maraviroc+raltegravir, each with fixed-dose tenofovir disoproxil fumarate/emtricitabine. Rectal and duodenal biopsies were obtained at baseline and at 9 months of ART. We performed a comprehensive assay of T-cell subsets by flow cytometry, T-cell density in intestinal biopsies, plasma and tissue concentrations of antiretroviral drugs by high-performance liquid chromatography/mass spectroscopy, and plasma interleukin-6 (IL-6), lipoteichoic acid (LTA), soluble CD14 (sCD14) and zonulin-1 each measured by ELISA. Total cell-associated HIV DNA was measured in PBMC and rectal and duodenal mononuclear cells. Twenty-six HIV-infected patients completed the follow-up. In the duodenum, the quadruple regimen resulted in greater CD8+ T-cell density decline, greater normalization of mucosal CCR5+CD4+ T-cells and increase of the naïve/memory CD8+ T-cell ratio, and a greater decline of sCD14 levels and duodenal HIV DNA levels (P = 0.004 and P = 0.067, respectively), with no changes in HIV RNA in plasma or tissue. Maraviroc showed the highest drug distribution to the gut tissue, and duodenal concentrations correlated well with other T-cell markers in duodenum, i.e., the CD4/CD8 ratio, %CD4+ and %CD8+ HLA-DR+CD38+ T-cells. Maraviroc use elicited greater activation of the mucosal naïve CD8+ T-cell subset, ameliorated the distribution of the CD8+ T-cell maturational subsets and induced higher improvement of zonulin-1 levels. These data suggest that combined CCR5 and integrase inhibitor based combination therapy in ART treatment naïve patients might more effectively reconstitute duodenal immunity, decrease inflammatory markers and impact on HIV persistence by cell-dependent mechanisms, and show unique effects of MVC in duodenal immunity driven by higher drug tissue penetration and possibly by class-dependent effects.
    Full-text · Article · Jan 2016 · PLoS Pathogens
  • Source
    • "Approximately 20% of cases arise in the periorbital or eyelid area, 40% on an extremity, and 10% on the trunk [4]. Immunodeficiency and immunosuppression, including patients with chronic lymphoid malignancies, HIV, and renal transplants may also play an important role in the development of MCC [3] [5] [6] [7]. Once MCC becomes metastatic, it is a highly aggressive skin cancer with a median survival of only 8 to 12 months. "

    Full-text · Article · Jan 2013 · Journal of Cancer Therapy
  • Source
    • "MCC has been recently shown to be associated with a virus, “Merkel-cell-polyomavirus” [4]. An increased risk of MCC has been reported among solid-organ transplant recipients [5, 6] and persons with HIV/AIDS [6, 7], and some studies have reported an association between MCC and other cancers, such as chronic lymphocytic leukemia [8–11]. MCC is considered to be highly aggressive and lethal [1, 2]; in fact, more than half of the persons with non-localized MCC die within 1 year of diagnosis [11]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Few population-based epidemiological data are available on Merkel cell carcinoma (MCC), a rare lethal non-melanoma skin cancer. We analysed multiple-cause-of-death records to describe MCC mortality and trends and the association with other primary cancers. We reviewed all 6,713,059 death certificates in Italy (1995-2006) to identify those mentioning MCC. We evaluated the association with other primary cancers by calculating the ratio of observed to expected deaths, using a standardized mortality ratio (SMR)-like analysis. We also evaluated the geographic distribution of deaths. We identified 351 death certificates with the mention of MCC. The age-adjusted mortality was 0.031/100,000, with a significant trend of increase and a slight north-south gradient. There was a significant deficit for solid cancers (SMR = 0.15) and a non-significant excess for lymphohematopoietic malignancies (SMR = 1.62). There were significant excesses for chronic lymphocytic leukemia (SMR = 4.07) and Waldenström's macroglobulinemia (SMR = 27.2) and a non-significant excess for chronic myeloid leukemia (SMR = 5.12). The increase in MCC mortality reflects the incidence trend in the literature. The association with chronic lymphocytic leukemia confirms the importance of immunologic factors in MCC. Regarding Waldenström's macroglobulinemia, an association with MCC has never been reported.
    Full-text · Article · Aug 2011 · Cancer Causes and Control
Show more