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Risk of skin cancer in HIV-infected patients: a Danish nationwide cohort study
 
 
  IN PRESS - March 2018
 
Download the PDF here
 
Download the PDF here
 
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IAS/2011: Skin Cancer in HIV: Doubled Rate of Nonmelanoma Skin Cancer With HIV in California Comparison http://www.natap.org/2011/IAS/IAS_37.htm
 
Published January 2013: HIV Infection Status, Immunodeficiency, and the Incidence of Non-Melanoma Skin Cancer

 
The incidence of non-melanoma skin cancers (NMSCs), including basal cell (BCC) or squamous cell carcinoma (SCC), is not well documented among HIV-positive (HIV+) individuals. We identified 6560 HIV+ and 36 821 HIV-negative (HIV−) non-Hispanic white adults who were enrolled and followed up in Kaiser Permanente Northern California from 1996 to 2008. The first biopsy-proven NMSCs diagnosed during follow-up were identified from pathology records. Poisson models estimated rate ratios that compared HIV+ (overall and stratified by recent CD4 T-cell counts and serum HIV RNA levels) with HIV− subjects and were adjusted for age, sex, smoking history, obesity diagnosis history, and census-based household income. Sensitivity analyses were adjusted for outpatient visits (ie, a proxy for screening). All statistical tests were two-sided. Results: The NMSC incidence rate was 1426 and 766 per 100 000 person-years for HIV+ and HIV− individuals, respectively, which corresponds with an adjusted rate ratio of 2.1 (95% confidence interval [CI] = 1.9 to 2.3). Similarly, the adjusted rate ratio for HIV+ vs HIV− subjects was 2.6 (95% CI = 2.1 to 3.2) for SCCs, and it was 2.1 (95% CI = 1.8 to 2.3) for BCCs. There was a statistically significant trend of higher rate ratios with lower recent CD4 counts among HIV+ subjects compared with HIV− subjects for SCCs (Ptrend < .001). Adjustment for number of outpatient visits did not affect the results. Conclusion: HIV+ subjects had a twofold higher incidence rate of NMSCs compared with HIV− subjects. SCCs but not BCCs were associated with immunodeficiency.
 
Pdf attached above
 
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Risk of skin cancer in HIV-infected patients: a Danish nationwide cohort study
 
IN PRESS - March 2018 - JAAD - Silje Haukali Omland, MD, PhD, Magnus Glinvad Ahlstrom, MD, Jan Gerstoft, MD, DMSc, Gitte Pedersen, MD, PhD, Rajesh Mohey, MD, PhD, Court Pedersen, MD, DMSc, Gitte Kronborg, MD, DMSc, Carsten Schade Larsen, MD, DMSc, Birgit Kvinesdal, MD, DMSc, Robert Gniadecki, MD, DMSc, Niels Obel, MD, DMSc, Lars Haukali Omland, MD, PhD, DMSc
 
"DISCUSSION: The increased risk of BCC was only seen in patients reporting MSM as route of infection. One could argue that the increased risk of BCC might be driven primarily by sun exposure in youth/adulthood not accounted for by the sibling model since previous data suggests that HIV-infected MSM might have an increased recreational UV exposure.12 Further, no association between BCC and immunosuppression was observed. Difference in lifestyle habits including traveling as well as occupation might also influence the risk; however, data on these parameters were not available for this study. For SCC the picture was somewhat the opposite. SCC seemed to be associated with more severe immunosuppression as reflected by lower nadir CD4 cell count. Further, the increased SCC risk was not restricted to any route of infection. This corresponds to data from other studies in HIV-infected individuals and in solid organ transplant recipients, where the incidence of SCC has been reported to be proportional to the level of immunosuppression. 5,14,15 Our results were somehow contradictory in terms of CD4 cell count with nadir, but not current CD4 cell count being associated with risk of SCC. We cannot conclude meaningfully on current CD4 cell count due to very wide CI, but it could be hypothesized that nadir CD4 count is indicative of immunosuppressive history and represents a time lag between immunosuppression and skin cancer while this exposure lag is not seen with current CD4 cell counts. Human papillomavirus (HPV) alpha is associated with cervical, anogenital-and oropharyngeal cancers. HPV beta has been detected in a proportion of cutaneous SCC, and a possible etiological role has been suggested, especially in the immunosuppressed individuals. However, no mechanism of carcinogenesis has yet been found. 16,17 A study from California (Siverberg, Kaiser) found a 2.6 fold increased risk of SCC and a 2.1-increased risk of BCC when comparing HIV-positive with HIV-negative patients.5 The risk of BCC was almost comparable to our results, while the risk of SCC was substantially higher in our study. Numerous factors could affect rates of SCC among both HIV-infected patients and their HIV negative counterparts, which in turn will affect the estimated relative risk of SCC comparing these two groups. In the study from California, SCCs in situ were included. Further, the Californian cohort was older and had a higher CD4 cell count - the latter probably contributes substantially to the lower risk of SCC observed in the American study. Unknown and residual confounding as well as unrecognized interaction between HIV and confounders might also affect the associations found. Finally, differences in sun exposure and skin type between California and Denmark might influence the results though one would expect this to apply for both HIV-infected and controls.
 
...............One of the main risk factors for developing skin cancer is UV-exposure. In our study, we assumed that skin type and level of sun exposure in childhood were comparable between siblings. We found no increase in BCC-, SCC- or MM-risk among siblings of HIV-infected patients compared with siblings of the matched background cohort; hence, the data did not support confounding by sun exposure in early childhood as an explanation of the increased risk of BCC and SCC among HIV-infected patients. However, since use of sunbeds mostly happens in youth/adulthood, this might differ between siblings. Therefore, an increased risk of KSC (keratinocyte skin cancers) in HIV-infected patients, but not their siblings, could be a result of either the immunosuppression caused by the HIV-infection or sunbed use in youth/adulthood. The increased risk of BCC was only seen in patients reporting MSM as route of infection. One could argue that the increased risk of BCC might be driven primarily by sun exposure in youth/adulthood not accounted for by the sibling model since previous data suggests that HIV-infected MSM might have an increased recreational UV exposure.12 Further, no association between BCC and immunosuppression was observed. Difference in lifestyle habits including traveling as well as occupation might also influence the risk; however, data on these parameters were not available for this study. For SCC the picture was somewhat the opposite. SCC seemed to be associated with more severe immunosuppression as reflected by lower nadir CD4 cell count. Further, the increased SCC risk was not restricted to any route of infection. This corresponds to data from other studies in HIV-infected individuals and in solid organ transplant recipients, where the incidence of SCC has been reported to be proportional."
 
Abstract
 
Background

 
The risk of skin cancer in HIV-infected patients has not been extensively studied.
 
Objective
 
To determine the risk of skin cancer in HIV-infected patients and compare it with the risk in the background population.
 
Methods
 
In a matched, nationwide population-based cohort study we compared the risk of skin cancer in 4280 HIV-infected patients from the Danish HIV cohort study with a background population cohort, according to the level of immunosuppression and route of transmission. Primary outcomes were time to first basal cell carcinoma (BCC), squamous cell carcinoma (SCC), or malignant melanoma (MM).
 
Results
 
HIV-infected patients had an increased risk of BCC and SCC with IRRs of 1.79 (95% CI 1.43 - 2.22) and 5.40 (95% CI 3.07 - 9.52), respectively, compared with the background population. We observed no increased risk of MM. Low nadir CD4 cell count was associated with an increased risk of SCC. The increased risk of BCC among HIV-infected patients was restricted to men who had sex with men.
 
Limitations
 
Observational design. Small number of patients with melanoma.
 
Conclusion
 
HIV-infected patients have an increased risk of BCC and SCC. Low nadir, but not current, CD4 cell count as a marker of immunosuppression was associated with an increased risk of SCC.
 
Background
 
Skin cancer risk is increased in immunocompromised individuals. 1,2 After the introduction of highly active antiretroviral therapy (HAART) the overall life expectancy for well-treated HIV-infected patients is approaching that of the background population.3 The immunological recovery resulting from HAART has lowered the incidence of AIDS defining cancers while there is a persistently increased risk of some non-AIDS defining cancers.4 Whether HIV-infected patients are at increased risk of skin cancer is not well documented partially since few countries provide reliable information on keratinocyte skin cancers (KSC), in particular basal cell carcinoma (BCC). A two-fold increased risk of BCC and squamous cell carcinoma (SCC) was demonstrated in a study of HIV-infected patients living in the US. 5 In this study, we aim to estimate the risk of non-AIDS defining skin cancer, both KSC (comprising BCC and SCC) and MM in HIV-infected patients compared with a sex- and age matched cohort from the background population as well as siblings of these two cohorts. This unique study design using high quality population based, nationwide data enabled us to address potential confounding by skin type and family related sun behaviour and to provide data on skin cancer risk in HIV-infected patients from more northern parts of the world.
 
Risk of BCC
 
The IR of BCC was 2.43 (95% CI: 2.00 - 2.95)/1000 PYR) in HIV-infected patient and 1.43 (95% CI: 1.30 -1.58) /1000 PYR in the matched background cohort with a difference of 1.00 (95% CI: 0.50 - 1.49)/1000 PYR (Table 2). Figure 1 illustrates the cumulative incidence of BCC. The risk of a BCC diagnosis was increased for the HIV infected patients (IRR 1.79 (95% CI: 1.43 - 2.22)). Siblings of HIV-infected patients did not have an increased risk of BCC compared with siblings of the matched background cohort (IRR: 1.02 (95% CI: 0.75 - 1.40)). Neither current nor nadir CD4 cell count were associated with risk of BCC (Table 3). The risk of BCC differed according to route of infection. Those, who reported MSM as the route of HIV transmission had an increased risk of BCC with IRR of 2.30 (95% CI: 1.76-3.02) compared with the matched background cohort. For other routes of HIV-infection, no increased risk of BCC was observed (Table 2).
 
Risk of SCC
 
The IR of SCC was 0.50 (95% CI: 0.32 - 0.77)/1000 PYR) in HIV-infected patient and 0.10 (95% CI: 0.07 -0.15)/1000 PYR in the matched background cohort with a difference of 0.40 (95% CI: 0.18 - 0.62)/1000 PYR (Table 2). Figure 2 illustrates the cumulative incidence of SCC. The risk of being diagnosed with SCC was increased among HIV-infected patients compared with the matched background cohort with an IRR of 5.40 (95% CI: 3.07 - 9.52) (Table 2). We did not detect any difference in risk of SCC when comparing siblings of HIV infected patients with siblings of the matched background cohort (IRR: 0.70 (95% CI: 0.09 - 5.66)). Nadir, but not current CD4 cell count was associated with a decreased risk of SCC (Table 3). The increased risk of SCC was observed in both MSM as well as HIV patients reporting heterosexual route of HIV transmission (Table 2).
 
Risk of MM
 
The risk of developing MM seemed not to be increased among HIV-infected patients (IRR of 0.60 (95% CI: 0.28 - 1.31)) or their siblings (IRR of 0.95 (95% CI: 0.55 - 1.61)) when compared with the matched background cohort and siblings of the matched background cohort, respectively. Since all diagnoses of MM among HIV-infected patients appeared when the CD4 cell count was <350 cells/μL no further investigation of the impact of immunosuppression was done.

 
 
 
 
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