Stratified Temporal Risk of Skin Cancer by Age Associated with Hydrochlorothiazide: A Retrospective Cohort Study Using the TriNetX Database

Hydrochlorothiazide (HCTZ) is known to have photosensitizing properties with recent FDA labeling updates warning of its increased risk of nonmelanoma skin cancer (NMSC). There are few and at times conflicting studies in the current literature on the topic, in particular with regard to melanoma associations and significant confounders. This retrospective cohort study utilizing the TriNetX database investigates age and temporal associations between the initiation of HCTZ as monotherapy for hypertension (HTN) and the diagnosis of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma. Six adult (age >18) cohorts were created with (1) HTN (ICD10: I10) as control and (2) HTN with HCTZ; then further stratified by age from 18 to 49 and 50 to 75. Outcomes assessed were BCC, cSCC, and melanoma at 5 and 10 years. HCTZ usage in cohorts aged 50 to 75 years old was significantly (p<0.05) associated with an increased risk ratio of BCC and cSCC at 5 and 10 years and with melanoma only at 10 years. This study refines prior reports of HCTZ usage associated with development of BCC and cSCC particularly in older adults while controlling for confounders such as concurrent antihypertensives and smoking. The association with melanoma in the older aged cohorts and with longer durations of HCTZ usage suggests a role for cumulative actinic damage among other risk factors. We highlight the need for increased dermatological surveillance and counseling among this vulnerable population, especially for those over the age of 50 on sustained HCTZ therapy.