[Penile carcinoma: the importance of histological classification and new treatment strategies].

Abstract

Penile carcinoma is a rare malignancy, predominantly derived from squamous epithelium, with a partially aggressive clinical course. The 2022 WHO classification distinguishes HPV-associated (HPV(+)) and HPV-independent (HPV(-)) subtypes, a differentiation that bears significant prognostic and therapeutic implications. HPV(-) carcinomas often develop as result of chronic inflammation, e.g. lichen sclerosus. While HPV(+) tumours, such as the warty subtype, often exhibit an indolent course, basaloid and sarcomatoid variants are associated with poor prognosis and an increased risk of metastasis.The prognostic value of HPV status alone is still inconsistent across studies. In contrast, p16 overexpression as surrogate marker for HPV infection, has been linked to improved survival outcomes. A combined assessment of HPV and p16 status is therefore recommended, particularly for therapeutic decision-making. In HPV(-) tumours, additional analysis of p53 expression is advisable, as TP53 mutations - frequently observed in this group - are associated with more aggressive tumour biology.Beyond conventional platinum-based chemotherapy, targeted therapies are gaining attention. Antibody-drug conjugates (ADCs), such as enfortumab vedotin (targeting Nectin-4) and sacituzumab govitecan (targeting Trop-2) have shown promising efficacy in other tumour types. Both targets are also expressed in penile carcinoma, and early clinical trials are underway. HER2 is expressed in a relevant proportion of cases and may be an additional therapeutic target.Immune checkpoint inhibitors like atezolizumab have so far demonstrated limited efficacy in penile cancer, despite high rates of PD-L1 expression. This discrepancy may be attributed to the immunosuppressive tumour microenvironment. EGFR-targeted monoclonal antibody therapies are also a potential treatment option.Accurate histopathological and molecular characterisation is critical for personalised treatment approaches and should become an integral component of the clinical management of penile carcinoma.