Implications of HPV infection on survival outcomes in patients with penile squamous cell carcinoma: Insights from a nationwide study.

Background: Human Papilloma Virus (HPV) infection is a favorable prognostic marker in certain cancers, particularly oropharyngeal and vulvar (SCC). Patients with pSCC have risk profile and clinical course like pSCC. However, the impact of HPV status on survival in pSCC remains uncertain. Methods: We conducted a retrospective study using the National Cancer Database and included patients with pSCC tested for HPV between 2004-2021. Survival outcomes were analyzed and reported as median overall survival (mOS, 95% CI). Multivariate analysis adjusting for age, disease stage, treatment modalities, and comorbidities, was performed using Cox proportional hazards models and reported as hazard ratios (HR, 95% CI). Results: Out of 1371 men with pSCC, 539 (39.3%) were HPV positive (HPV +ve). At diagnosis, most HPV +ve men with pSCC presented with early-stage cancer(I-III), and 6% were stage IV. The mOS for HPV +ve patients was 123.96 months (98.96 - 148.40) vs. 104.38 months (89.13 - 115.98) in HPV negative patients with pSCC (P=0.01). In the adjusted analysis, the presence of HPV infection was associated with HR for death of 0.79 (0.65-0.98; P = 0.03) compared to patients without HPV (table). Conclusions: HPV infection in patients with pSCC is associated with improved survival. These findings highlight HPV status as a prognostic Indicator in pSCC irrespective of clinical profile. Therefore, testing for HPV at the time of diagnosis should be performed routinely in patients with pSCC.