Carcinogenic biomarkers of exposure in the urine of heated tobacco product users associated with bladder cancer: A systematic review

To identify biomarkers of exposure present in Heated Tobacco Products (HTPs) users’ urine which are associated with bladder cancer and to compare quantitative biomarker levels to those seen in combustible cigarette users. A systematic literature review was conducted in December 2020 with no date limits. Relevant studies that reported quantitative urinary biomarker of exposure in HTP users were included. Biomarkers and their parent compounds were classified by carcinogenicity according to the International Agency for Research on Cancer Monographs and were cross-referenced with the Collaborative on Health and the Environment Toxicant and Disease Database to determine associations with bladder cancer. Our literature search identified 561 articles and 30 clinical trial reports. 11 studies met inclusion criteria. These studies identified 29 biomarkers of exposure present in HTP users’ urine, which reflect exposure to 21 unique parent compounds. Of these parent compounds, 14 are carcinogens and 10 have a known link to bladder cancer. HTP users’ biomarkers of exposure were present at lower levels than combustible cigarette users but higher than never-smokers. Biomarkers of exposure to bladder carcinogens are present in the urine of HTP users. While levels of these biomarkers appear to be lower than combustible cigarette users, chronic urothelial exposure to bladder carcinogens is concerning and degree of bladder cancer risk remains unknown. Further long-term study is needed to elucidate the bladder cancer risk of HTP use.