Association between hydrochlorothiazide and the risk of in situ and invasive squamous cell skin carcinoma and basal cell carcinoma: A population-based case-control study

Background: Population-based studies analyzing hydrochlorothiazide's (HCTZ's) effect on keratinocyte carcinoma, and particularly invasive squamous cell carcinoma (SCC), are lacking. Objectives: To characterize the association between HCTZ use and invasive SCC, SCC in situ (SCCis), and basal cell carcinoma (BCC). Methods: This population-based case-control study included all 6880 patients diagnosed with first-time BCC, SCCis, and invasive SCC between 2003 and 2017 in Iceland and 69,620 population controls. Conditional logistic regression analyses were used to calculate multivariate odds ratios (ORs) for keratinocyte carcinoma associated with HCTZ use. Results: A cumulative HCTZ dose above 37,500 mg was associated with increased risk of invasive SCC (OR, 1.69; 95% confidence interval [CI], 1.04-2.74). Users of HCTZ also had an increased risk of SCCis (OR, 1.24; 95% CI, 1.01-1.52) and BCC (OR, 1.14; 95% CI, 1.02-1.29). Limitations: Limitations include this study's retrospective nature with the resulting inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities. Conclusions: High cumulative exposure to HCTZ is associated with the development of keratinocyte carcinoma and, most importantly, invasive SCC. Sun protective behaviors alone may not eliminate the carcinogenic potential of HCTZ.