Use of voriconazole is associated with an increased risk for cutaneous squamous cell carcinoma (SCC) in patients with lung transplant (LT) or hematopoietic cell transplant (HCT), according to a recent systematic literature review and meta-analysis published in the Journal of the American Academy of Dermatology.

The systematic literature review and meta-analysis were conducted to clarify the association between voriconazole use and SCC risk. PubMed and Embase databases were searched for relevant literature published through September 2017. Reference lists from selected literature were also reviewed.

Eight observational studies (N=3710), 6 of which provided adequate data, were selected for review. The inclusion criteria were as follows: both prospective and retrospective observational studies and evaluation of the risk between voriconazole use and SCC and basal cell carcinoma (BCC often follows SCC in cases of nonmelanoma skin cancer).


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Pooled relative risk (RR) was calculated at a 95% confidence interval (CI) within a random-effects model to account for statistical heterogeneity (quantified using the I2 statistic) among the studies. A sensitivity analysis was conducted, followed by a cumulative meta-analysis based on the publication date. Begg’s and Egger’s tests and a funnel plot were used to identify potential cases of publication bias.

The relative risk [RR] for SCC upon voriconazole use was calculated as 1.86 (95% CI, 1.36-2.55). When adjusted for sun exposure, RR was calculated as 2.42 (95% CI, 1.38-4.22). No substantial evidence of publication bias was found according to the Begg’s test (P =.81) or Egger’s test (P =.98) or upon visual analysis of the funnel plot. After reviewing 2 studies of 41 basal cell carcinoma (BCC) cases among 1386 individuals, no significant association between BCC and voriconazole risk was found (RR 0.84; 95% CI, 0.41-1.71).  

The authors noted a considerable heterogeneity in the retrospective studies included in the review and analysis. For example, the definition of voriconazole treatment varied among the studies, and the residual confounding variables, such as skin type, were present. The authors recommend larger studies with greater voriconazole exposure details to corroborate the findings.

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Reference

Tang H, Shi W, Song Y, Han J. Voriconazole exposure and risk of cutaneous squamous cell carcinoma among lung or hematopoietic cell transplant patients: A systematic review and meta-analysis. [published August 18, 2018]. J Am Acad Dermatol. doi:10.1016/j.jaad.2018.08.010