Penile cancer is rare but associated with a high morbidity and mortality once metastasized. Besides presenting a fundamental overview of penile cancer, the current literature on key players associated with the pathogenesis of penile cancer including common labor chemistry parameters [neutrophil to lymphocyte ratio (NLR) and C-reactive protein CrP)], programmed cell death 1 (PD1)/PD ligand 1 (PD-L1), regulatory T cells (Tregs), forkhead box protein 3 (FoxP3, also known as scurfin), Ki-67 (also known as MKI67), protein 53 (p53), and pericytes has been reviewed and summarized. Furthermore, future directions and an overview of ongoing clinical trials are provided to highlight potential avenues that could improve cancer-specific and overall survival.

Keywords: C-reactive protein; Cytotoxic T lymphocyte-associated protein 4; Epidermal growth factor receptor; FoxP3; Human papilloma virus; Ki-67; Neutrophil to lymphocyte ratio; P53; PD ligand 1; Pericytes; Programmed cell death 1; Regulatory T cells; Squamous cell carcinoma; Tumor microenvironment; Vascular endothelial growth factor.