Overview of the genetic pathogenesis of penile cancer

Penile cancer is a rare malignancy that predominantly affects males over the age of 55 in developing countries. It accounts for less than 1% of cancers in men in the United States, but 10% to 20% of cancers in some African, Asian, and South American countries. With diagnosis often occurring at stage 4, penile cancer can cause significant morbidity and mortality. Due to its rare nature, medical literature containing data elucidating the genetic pathogenesis of penile cancer is limited. This review aims to describe the following genetic markers implicated in the pathogenesis of penile cancer: HPV, p53, BRCA2, CSN1, FAT1, MYCN, FAK, and STK11. We synthesized data from the last 20 years describing the association between these genes and cancer-specific survival, mortality, metastasis, and tumor progression rates. Additionally, this is the first review to describe the potential mechanisms by which each of the aforementioned genes/viruses contributes to penile cancer tumorigenesis. We also indicate the therapeutic relevance of each gene/virus with regard to their response to radiotherapy, chemotherapy, or immunotherapy.