Central European Journal of Urology · May 14, 2026

Comparison of carcinogen biomarkers in electronic cigarette users versus conventional cigarette users in the development of urothelial cancer: A systematic review and meta-analysis

By Warli MH, Warli SM, Kadar DD et al.

INTRODUCTION: Despite the increasing use of electronic cigarettes globally, limited understanding persists regarding their effects on urothelial cancer. This study aimed to conduct a systematic review and meta-analysis comparing carcinogen exposure associated with urothelial cancer development in electronic and conventional cigarette users. MATERIAL AND METHODS: The study was conducted through a systematic search of multiple databases adhering to PRISMA guidelines. Eligible articles were evaluated for quality using established scoring systems, and data were synthesized using a random effect model. Heterogeneity was assessed, and sensitivity analysis was conducted. Included carcinogen substances were identified using the Collaborative on Health and the Environment Toxicant and Disease Database, including their potential association with urothelial cancer. RESULTS: The search identified 1,221 records, of which 14 observational studies involving 14,065 participants met the inclusion criteria. A total of 28 carcinogenic or potentially carcinogenic substances were detected in the urine of electronic cigarette users and compared with conventional cigarette users. These included compounds strongly associated with urothelial cancer (aromatic hydrocarbons and 2-naphthylamine), compounds with a limited association (tobacco-specific nitrosamines and metals), and compounds strongly associated with cancer in general (volatile organic compounds). The meta-analysis showed that only 2-hydroxyfluorene was significantly lower in electronic cigarette users compared with conventional cigarette users (SMD -0.53; 95% CI: from -0.60 to -0.46; p <0.00001). Other biomarkers - including cotinine, 1-hydroxypyrene, 2-naphthol, hydroxyfluorenes, NNAL, AAMA, and MHBMA - showed comparable concentrations between the two groups. CONCLUSIONS: Although several carcinogenic biomarkers appear at lower concentrations than in conventional cigarette users, multiple urothelial cancer-associated carcinogens remain detectable in the urine of electronic cigarette users, suggesting potential long-term carcinogenic risk.

doi.org/10.5173/ceju.2026.0020Open accessPubMed 42903726Populations