Programmed death ligand 1 expression and human papillomavirus status: penile cancer prognostic factors and new therapeutic opportunities

Penile cancer is a rare malignancy with limited treatment options beyond local resection and lymph node dissection. Risk factors for penile cancer development include phimosis, smoking, lack of circumcision, and human papillomavirus (HPV) infection. Based on cancer incidence and histologic subtyping, penile cancer is often stratified by HPV status. Cohort studies have found that HPV positive tumors have better prognosis. The success of HPV vaccination for the prevention of cervical cancer and genital warts has resulted in new recommendations for vaccination of men. However, these efforts would not be expected to improve outcomes in men with HPV negative tumors. New therapeutic strategies are needed to improve outcomes in men with advanced penile cancer. Programmed death ligand 1 (PD-L1) targeted treatments have been successful in other malignancies including melanoma and non-small cell lung cancer. Determining the frequency of PD-L1 positive tumor cells in penile cancer is needed to establish the potential benefit of using these targeted therapies in penile cancer patients. Evaluating the relationship between PD-L1 expression and HPV status may provide support for the proposed dual pathway to malignant transformation. Comparing PD-L1 status to HPV status should add another prognostic factor while expanding the therapeutic options for this malignancy.