Prognostic Significance of p16 and Its Relationship with Human Papillomavirus Status in Patients with Penile Squamous Cell Carcinoma: Results of 5 Years Follow-Up

Simple Summary Penile Squamous Cell Carcinoma (PSCC) is a rare but aggressive cancer and approximately 30-50% of cases are associated with high risk human papillomavirus (HR-HPV). HR-HPV infection has been shown to correlate with expression of protein p16(INK4a) (p16). We wanted to determine if HPV-HR or p16 expression is associated with better outcomes in PSCC patients; therefore, we analyzed 143 patients with a diagnosis of PSCC and available tissue was analyzed for p16(INK4a) expression and HR-HPV status. Patients with p16+ tumors had a significantly longer median cancer specific survival in comparison to the p16-group (p = 0.004), with respective 5-year cancer specific survival probability of 88% (95% CI; 0.84, 1) versus 58% (95% CI; 0.55, 0.76; p = 0.004). HPV status did not predict survival outcomes. Penile Squamous Cell Carcinoma (PSCC) is associated with high-risk human papillomavirus (HR-HPV). The immunohistochemical (IHC) test for p16(INK4a) (p16) is highly correlated with HR-HPV expression in other SCCs. To investigate whether the expression of p16 IHC or HR-HPV is associated with survival in PSCC, we conducted a single institution analysis of 143 patients with a diagnosis of PSCC and, available tissue were tested for p16 IHC staining patterns, histological subtype, tumor grade, and lymphovascular invasion (LVI) by an experienced pathologist. HR-HPV status using the Cobas PCR Assay or the RNAScope high-risk HPV in situ hybridization kit were also assessed. Patient characteristics were summarized using descriptive statistics of clinico-pathologic variables. Kaplan-Meier was used to estimate median overall survival (OS), cancer specific survival (CSS) and correlated with HPV, p16, and other study variables. Patients with p16+ tumors had a significantly longer median CSS in comparison to the p16- group (p = 0.004), with respective 5-year CSS probability of 88% (95% CI; 0.84, 1) versus 58% (95% CI; 0.55, 0.76; p = 0.004). HPV status did not predict survival outcomes. Multivariable analysis with respect to OS and CSS, showed that p16+ status was associated with a lower risk of death (HR = 0.36, 95%CI; 0.20-0.67, p = 0.001), and improved CSS (HR = 0.20, 95% CI; 0.07-0.54, p = 0.002) after adjusting for covariates. In conclusion, tumor p16 status via IHC was an easy to perform independent prognostic factor for OS and CSS that correlates with HR-HPV expression.

Automated summary

In patients with penile squamous cell carcinoma, the expression of p16 is associated with better outcomes, while HPV status does not predict survival outcomes.