eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2025-12-30 18 4 3008 3016 10.13005/bpj/3313 69655 article Desak Putu Oki Lestari 1 Analysa 2 Ni Wayan Armerinayanti 3 Ni Putu Diah Witari 4 Indah Budiapsari 5 I Nyoman Putu Riasa 6 Department of Pathological Anatomy, Faculty of Medicine and Health Sciences, Universitas Warmadewa, Bali, Indonesia Department of Pathological Anatomy, Tabanan Hospital, Bali, Indonesia Department of Pathological Anatomy, Faculty of Medicine and Health Sciences, Universitas Warmadewa, Bali, Indonesia Department of Histology, Faculty of Medicine and Health Sciences, Universitas Warmadewa, Bali, Indonesia Department of Parasitology, Faculty of Medicine and Health Sciences, Universitas Warmadewa, Bali, Indonesia Department of Plastic Surgery, Faculty of Medicine, Universitas Udayana, Bali, Indonesia Persistent infection of high risk human papilloma virus (HPV) is a recognized driver oncogenesis in penile cancer, often characterized by upregulation of p16 and immune evasion via programmed death-ligand 1 (PD-L1) expression. This study aimed to assess the prognostic significance of p16 and PD-L1 in advanced penile cancer. Methods: A total of 80 cases of advanced penile cancer were retrospectively evaluated. Expression of p16 and PD-L1 was assessed by immunohistochemistry. Various clinicopathological parameters, such as patient age, tumor dimensions, histopathological grading, evidence of vascular invasion, and presence of lymphatic metastasis, were systematically evaluated in relation to PD-L1 overexpression. PD-L1 overexpression was observed in 37 (46.25%) of cases. PD-L1 positivity was significantly higher in p16 positive tumors (57.5%) than in p16 negative cases (35%) (p=0.044). Elevated PD-L1 expression strongly correlated with increased tumor dimension (p=0.002), advanced  histological grade (p=0.000), the presence of vascular invasion (p=0.001), and lymphatic node involvement (p=0.000). PD-L1 overexpression was not significantly associated with the age of patients (p=0.932). PD-L1 and p16 are associated with clinicopathological features in advanced penile squamous cell carcinoma and may serve as prognostic biomarkers. Further multi-institutional studies are  needed to clarify their predictive value for tailoring immunotherapy in penile cancer. https://biomedpharmajournal.org/vol18no4/prognostic-role-of-programmed-death-ligand-1-and-p16-in-advanced-penile-cancer/ HPV P16 PDL-1 penile cancer SCC