Our aim is to investigate if waterpipe smokers might have a distinct mutational profile and higher mutational load and in their bladder cancers when compared to those in cigarette smokers.  Tumors with high mutational load are likely more immunogenic. This suggests that tumor mutational load could be potential predictive biomarker for PD-1/PDL1 blockade therapy which could offer a targeted and more effective treatment for WPS bladder cancer patients.