Penile squamous cell carcinoma (pSCC) is a rare cancer associated with a relatively poor prognosis. The WHO classifies pSCC into HPV-associated and HPV-independent subtypes, with HPV-positive pSCCs showing slightly better outcomes. A key negative prognostic marker is TP53 mutation. The aim of this study was to evaluate the concordance of (1) p16 immunohistochemistry with HPV status determined by PCR, (2) p53 immunohistochemistry with TP53 mutational status obtained by NGS, and (3) prognostic impact of overexpression and null phenotype p53 immunohistochemistry profiles. Analyzing invasive pSCC from 209 patients, we assessed concordance between p16 immunohistochemistry and HPV status (n = 132) determined by quantitative PCR, obtaining Cohen's kappa Κ = 0.62 (p < 0.0001). For p53 immunohistochemistry versus TP53 status by NGS (n = 145), Cohen's kappa reached Κ = 0.693 (p < 0.0001). We found worse overall survival (Hazard ratio = 3.33, 95% CIs 1.92-5.56, p < 0.0001) in p53 mutated cases (n = 38, both overexpression and null phenotype) compared to wild type (n = 171), but without a significant difference between both mutated profiles. Both HPV status and p53 profile can be reliably assessed by immunohistochemistry with substantial agreement. Patients with a mutated p53 profile showed significantly worse survival, irrespective of the mutated profile variant.
Pathology international. 2026 Jun [Epub]
Jan Hrudka, Jan Hojný, Eva Krkavcová, Jiří Dvořák, Zuzana Prouzová, Michaela Kendall Bártů, Nicolette Zavillová, David Čapka, Radoslav Matěj, Petr Waldauf
Department of Pathology, 3rd Faculty of Medicine, Charles University, University Hospital Kralovske Vinohrady, Prague, Czech Republic., Department of Pathology, 1st Faculty of Medicine, Charles University, General University Hospital, Prague, Czech Republic., Department of Urology, 3rd Faculty of Medicine, Charles University, Thomayer University Hospital, Prague, Czech Republic., Department of Urology, 3rd Faculty of Medicine, Charles University, University Hospital Kralovske Vinohrady, Prague, Czech Republic., Department of Anaesthesia and Intensive Care Medicine, 3rd Faculty of Medicine, Charles University, University Hospital Kralovske Vinohrady, Prague, Czech Republic.