Schistosoma haematobium
infection can lead to
squamous cell carcinomas (SCC) of the bladder. Whether this also applies to more common
urinary tract infections (UTIs) is unclear. We therefore aimed to investigate the association between UTIs, reflected by the use of specific
antibiotics and risk of SCC of the bladder. We conducted a Danish nationwide case-control study and identified histologically verified
bladder cancer cases (2000-2015; n = 12,271) and age- and sex-matched
cancer-free controls. We computed odds ratios (
ORs) with 95% confidence intervals (CI) associating the use of UTI-specific
antibiotics with SCC
bladder cancer, using conditional logistic regression. We applied a 2-year lag-time to minimize reverse causation. To aid interpretation, similar analyses were performed for other
bladder cancer types and other
antibiotics. We identified 333 SCC cases (2.7% of all
bladder cancers). Compared to no use (0-1 prescription), high-use (≥10 prescriptions) of UTI-specific
antibiotics was associated with SCC with an OR of 11.4 (CI 7.6-17.2) and a clear dose-response pattern (ptrend < 0.001). Use of
phenoxymethylpenicillin, an
antibiotic not used against UTIs, was not associated with SCC after adjustment for use of UTI-specific
antibiotics (OR 0.5). Furthermore, UTI-specific
antibiotic use was not associated with urothelial
carcinomas (n = 11,029; OR 1.13; CI 0.97-1.32). Excluding patients with known
urogenital disease did not influence the SCC estimates (overall OR 10.8; CI 6.2-18.9). Data on smoking were lacking, however, a quantitative bias analysis suggested this to be of limited importance. In conclusion, common UTIs are strong, dose-dependent and specifically associated with risk of SCC of the bladder.