Penile squamous cell carcinoma (pSCC) is a rare and aggressive malignancy with limited success of immune-checkpoint inhibitors (ICIs) Half of pScc cases are associated with human papillomavirus (HPV) infection . HPV16/18+ tumors were exclusively found to be the most common mutations . Increased tumor mutational burden could serve as a biomarker for predicting therapeutic response to ICI-based therapies .