Peniskarzinom: Die Bedeutung der histologischen Klassifikation und neue Behandlungsansätze

Zusammenfassung

Das Peniskarzinom ist ein seltener, meist aus Plattenepithel hervorgehender Tumor mit teils aggressivem Verlauf. Die WHO-Klassifikation 2022 unterscheidet HPV-assoziierte (HPV(+)) von HPV-unabhängigen (HPV(−)) Subtypen, was prognostisch und therapeutisch relevant ist. HPV(-) entstehen meist auf dem Boden einer chronischen Entzündung, zB bei Lichen sclerosus. Während HPV(+) Tumoren wie der warzige Typ eher indolent verlaufen, zeigen andere histologische Subtypen wie das basaloide oder sarkomatoide Karzinom eine ungünstiges Prognose mit erhöhter Metastasierungsrate.

Der alleinige HPV-Status zeigt in Studien eine uneinheitliche prognostische Aussagekraft. Dagegen ist eine p16-Überexpression als Surrogatmarker einer HPV-Positivität mit verbessertem Überleben assoziiert. Als kombinierter Marker empfiehlt sich die Analyse von HPV und p16, insbesondere zur Therapieentscheidung. Bei HPV(−) Tumoren ist ergänzend eine p53-Analyse sinnvoll, da hier häufiger TP53-Mutationen vorliegen, die mit aggressiverer Tumorbiologie einhergehen.

Neben konventioneller Chemotherapie rücken zielgerichtete Therapien in den Fokus. Antikörper-Drug-Konjugate (ADCs) wie Enfortumab-Vedotin (Zielantigen Nectin-4) und Sacituzumab-Govitecan (Zielantigen Trop-2) zeigen vielversprechende Ergebnisse in anderen Entitäten. Beide Zielstrukturen werden auch beim Peniskarzinom exprimiert. Erste Studien zur Wirksamkeit werden aktuell durchgeführt. Auch Her-2 ist in einem relevanten Anteil exprimiert und könnte therapeutisch nutzbar sein.

Immuncheckpoint-Inhibitoren wie Atezolizumab zeigten bislang nur begrenzte Wirksamkeit, trotz hoher PD-L1-Expressionsraten. Ein Grund dafür ist vermutlich das immunsuppressive Tumormikromilieu. Auch EGFR-Antikörpertherapien stellen eine potenzielle Option dar.

Die präzise histologische und molekulare Charakterisierung des Peniskarzinoms ist essenziell für eine individualisierte Therapie und sollte künftig integraler Bestandteil der klinischen Praxis sein.

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.

Schlüsselwörter

Plattenepithelkarzinom - HPV - Lichen Sclerosus - p53 - Antikörper-Wirkstoff-Konjugate (ADC)

Keywords

Squamous cell carcinoma - lichen sclerosus - HPV - antibody-drug-conjugates (ADC) - p53

Publication History

Received: 30 April 2025

Accepted: 17 June 2025

Article published online:
24 July 2025

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