High-risk human papilloma virus status & outcomes for penile squamous cell carcinoma: A single institution experience

Objectives: There is a paucity of data on North American cohorts of patients with penile squamous cell carcinoma (pSCC). Herein, we aimed to assess the sensitivity of various modalities to identify human papillomavirus (HPV) status, determine the prevalence of high-risk HPV–positivity, and evaluate the prognostic impact of relevant clinicopathologic variables. Methods: Patients with pSCC (n = 121) consecutively treated with partial/total penectomy (2000–2022) at a single institution were included. HPV status (based on immunohistochemistry [IHC], in situ hybridization [ISH], and panviral metagenomic sequencing [PMS]), histologic features, and outcomes were reviewed. Outcome events included death due to disease and progression. Results: The majority of patients were white (105/121, 86.8%). Thirty-seven (30.6%) were high-risk HPV–positive, and morphologic evaluation had a sensitivity of 97.3% (95% confidence interval [CI], 86.2–99.5) for predicting high-risk HPV status compared to IHC/ISH/PMS. Disease progression was more common among high-risk HPV–negative compared to high-risk HPV–positive patients (HR 2.74, CI 1.12–8.23, P = 0.03). Moreover, among high-risk HPV–negative patients, those with moderate-poorly differentiated tumors had increased disease-specific mortality (32.6%, CI 17.1–48.1) compared to those with well-differentiated tumors (0%). Among high-risk HPV–positive patients, those with basaloid morphology had lower disease-specific mortality (0% vs 14.4%, CI 0.0–33.1). Conclusions: We demonstrate high-risk HPV–positivity in approximately one-third of patients with pSCC. Morphologic evaluation alone had a high sensitivity in correctly determining HPV status. Our results suggest that high-risk HPV status and morphologic features (differentiation in high-risk HPV–negative, and basaloid subtype in high-risk HPV–positive pSCC) may have prognostic value.