Bedeutung von HPV-Status und p16 für die Prognose des Peniskarzinoms

Zusammenfassung

Hintergrund Das Peniskarzinom ist eine seltene, v.a. im metastasierten Stadium jedoch häufig tödliche Tumorerkrankung. Die meisten Daten zu Prognosefaktoren des Peniskarzinoms basieren auf kleinen Patientenkohorten, und selbst Metaanalysen sind hinsichtlich der Patientenzahlen meist eingeschränkt. Es fehlt an suffizienten Parametern, um das Metastasierungspotenzial der Tumoren vorhersagen zu können. Weiterhin unklar ist die Rolle des HPV-Status für die Prognoseabschätzung und in diesem Zusammenhang auch von p16INK4a.

Material und Methoden In dieser Studie wurden 236 Patienten aus einer internationalen multizentrischen Kohorte hinsichtlich der histologischen Subtypen, des HPV- und p16-Status sowie weiterer klinischer Parameter untersucht. Der HPV-Status wurde nur bei Nachweis von HPV mittels PCR sowie einem positiven p16-Status als HPV-positiv gewertet. Die statistische Analyse erfolgte mittels Kaplan-Meier-Methode sowie dem Log-rank-Test und einer uni- und multivariablen Analyse mittels Cox-Regressionsmodell.

Ergebnisse Ein positiver HPV-Status war weder für das metastasenfreie (MFS), noch das tumorspezifische (CSS) oder das Gesamtüberleben (OS) ein signifikanter Parameter. Bei p16-positiven Tumoren zeigte sich ein signifikant besseres MFS (p = 0,026), was sich ebenfalls in der Subgruppenanalyse der HPV-negativen Tumoren bestätigte (p = 0,037) ohne Unterschiede im CSS oder OS. Im „Usual Type“ bestand ebenfalls eine positive Tendenz im MFS, jedoch ohne statistische Signifikanz (p = 0,070). p16-positive Tumoren waren in der multivariablen Cox-Regression mit einem hochsignifikant besseren MFS (Hazard Ratio 0,3; p = 0,004) assoziiert, während Patienten mit einem pT1b-Tumorstadium oder fortgeschrittener Lymphknotenmetastasierung ein signifikant schlechteres Überleben aufzeigten. In der multivariablen Analyse der HPV-negativen Tumoren war der p16-Status ebenfalls mit einem signifikanten Unterschied im MFS assoziiert (Hazard Ratio 0,2; p = 0,007).

Schlussfolgerung Der HPV-Status scheint nur von geringer prognostischer Relevanz zu sein, während der p16-Status eine wichtige Rolle in der Prognoseabschätzung einnimmt. So ist die Expression von p16INK4a mit einem signifikant besseren MFS assoziiert. Insbesondere in HPV-negativen Tumoren sollte der p16-Status hinsichtlich der prognostischen Wertigkeit und damit weiterführend auch hinsichtlich der Therapieentscheidung evaluiert werden.

Abstract

Background Penile cancer is a rare but often lethal tumour disease, especially in the metastatic stage. Most data on prognostic factors for penile cancer are based on small patient cohorts, and even meta-analyses are mostly limited in terms of patient numbers. There is a lack of sufficient parameters to predict the metastatic risk of these tumours. Furthermore, the role of the HPV status for the prognosis, and, in this regard, of p16INK4a is still unclear.

Material and Methods In this study, 236 patients from an international multicentre cohort were analysed with regard to histological subtypes, HPV and p16 status, and other clinical parameters. The HPV status was only graded as HPV-positive if HPV was detected by PCR and the p16 status defined by immunochemistry was positive. The statistical analysis was carried out using the Kaplan-Meier method as well as the log-rank test and a univariable and multivariable analysis using the Cox regression model.

Results A positive HPV status was not a significant parameter for either metastasis-free (MFS), tumour-specific (CSS) or overall survival (OS). p16-positive tumours showed a significantly better MFS (p=0.026), which was also confirmed in the subgroup analysis of HPV-negative tumours (p=0.037) without differences in CSS or OS. In the usual type, there was also a trend towards an improved MFS, but without statistical significance (p=0.070). p16-positive tumours were associated with a highly significantly better MFS (hazard ratio 0.3; p=0.004) in the multivariable Cox regression, while patients with a pT1b tumour stage or advanced lymph node metastasis showed a significantly worse survival. In the multivariable analysis of HPV-negative tumours, p16 status was also confirmed as an independent predictor of MFS (Hazard ratio 0.2; p=0.007).

Conclusion HPV status alone seems to be lacking prognostic relevance. In contrast, p16 status was confirmed as an independent prognostic factor. Thus, the expression of p16INK4a is associated with a significantly better MFS. Especially in HPV-negative tumours, the p16 status should be evaluated with regard to the prognostic value and thus also with a view to the treatment decision.

Schlüsselwörter

Peniskarzinom - HPV - p16 - Usual Type

Keywords

penile cancer - HPV - p16 - usual type

Publikationsverlauf

Eingereicht: 09. März 2023

Angenommen nach Revision: 25. Mai 2023

Artikel online veröffentlicht:
04. August 2023

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