To Örebro University

BACKGROUND AND OBJECTIVE: To improve treatment for patients with penile cancer, there is a need for prognostic and treatment predictive biomarkers. The objective of this study was to examine the expression of checkpoint proteins (programmed cell death ligand 1 [PD-L1], T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain [TIGIT], and cluster of differentiation 155 [CD155]) and human papillomavirus (HPV) status in primary tumors of penile cancer patients with indication for perioperative oncological treatment. As a secondary aim, we evaluated the associations between these biomarkers and penile cancer-specific survival.

METHODS: Fifty-two patients who underwent surgical treatment during 2009-2018 were included. HPV status was determined by polymerase chain reaction, and tissue microarray sections from primary tumors were subjected to immunohistochemistry to evaluate the expression of PD-L1, TIGIT, and CD155.

KEY FINDINGS AND LIMITATIONS: PD-L1, TIGIT, and CD155 were expressed widely. Specifically, 75% of patients had PD-L1-positive tumors, 80% had TIGIT-positive tumors, and 98% had CD155-positive tumors. Additionally, 47% of patients had HPV-positive tumors. Patients with HPV-positive tumors had better survival than those with HPV-negative tumors. Patients with indication for perioperative oncological therapy who received such treatment and whose tumors exhibited low PD-L1 expression demonstrated better survival than those with higher PD-L1 expression levels. The main limitations of this study include the small number of patients, retrospective design, and use of tissue microarrays rather than whole tissue sections.

CONCLUSIONS AND CLINICAL IMPLICATIONS: We found high expressions of the investigated checkpoint proteins, suggesting an immunosuppressed tumor microenvironment in patients with advanced penile cancer. These findings imply that checkpoint proteins could serve as prognostic and treatment predictive biomarkers. Patients with HPV-positive tumors had better prognosis.

PATIENT SUMMARY: In this report, we investigated tumor tissue from patients with penile cancer and identified a high prevalence of proteins that play an important role in the immune system's defense against cancer. The findings suggest that these proteins can be important in understanding and developing treatments for patients with lymph node metastasized penile cancer.