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.

中文翻译：

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尿路感染和鳞状细胞癌膀胱癌的风险：丹麦一项全国病例对照研究。

血吸虫血吸虫感染可导致膀胱鳞状细胞癌（SCC）。尚不清楚这是否还适用于更常见的尿路感染（UTI）。因此，我们旨在研究UTI之间的联系，这通过使用特定的抗生素和膀胱SCC的风险反映出来。我们进行了一项丹麦全国性病例对照研究，确定了经组织学验证的膀胱癌病例（2000-2015年； n = 12,271）以及年龄和性别相匹配的无癌对照。我们使用条件对数回归，计算了将UTI特异性抗生素与SCC膀胱癌的使用相关联的比值比（OR）与95％的置信区间（CI）。我们应用了2年的滞后时间以最小化反向因果关系。为了帮助解释，对其他类型的膀胱癌和其他抗生素进行了类似的分析。我们确定了333例SCC病例（占所有膀胱癌的2.7％）。与不使用（0-1个处方）相比，大量使用（≥10个处方）的UTI特异性抗生素与SCC相关，OR值为11.4（CI 7.6-17.2），并且有明显的剂量反应模式（ptrend <0.001） ）。调整使用UTI特异性抗生素后，苯氧甲基青霉素（一种未用于抗UTI的抗生素）与SCC无关（OR 0.5）。此外，UTI特异性抗生素的使用与尿路上皮癌无关（n = 11,029； OR 1.13； CI 0.97-1.32）。排除患有已知泌尿生殖系统疾病的患者不会影响SCC评估（总体OR 10.8； CI 6.2-18.9）。缺乏吸烟数据，但是，定量偏倚分析表明这重要性有限。总而言之，常见的UTI很强，