ctHPV-DNA-basierte Präzisionsonkologie für Patienten mit Oropharynxkarzinom – wo stehen wir?

Zusammenfassung

Das humane Papillomavirus (HPV) ist im Kopf-Hals-Bereich ein gesicherter ätiologischer Faktor für die Entstehung von oropharyngealen Plattenepithelkarzinomen (engl. OPSCC). Die gute Überlebensrate rechtfertigt die derzeitige Diskussion einer Therapiedeeskalation für Patienten mit einem geringeren Risikoprofil. Ungeachtet des immunhistochemisch nachweisbaren Biomarkers p16INK4a besteht ein hoher Bedarf an diagnostischen und prognostischen Biomarkern, um eine valide Risikostratifizierung und Überwachung der Patienten unter Therapie und in der Nachsorge ermöglichen zu können. Die Liquid Biopsy, insbesondere in Form von Plasmaproben, hat aus diesem Grund in den letzten Jahren an Bedeutung gewonnen und wird bereits bei Epstein-Barr-Virus-assoziierten Nasopharynxkarzinomen zum Monitoring der Virus-DNA eingesetzt. Die zirkulierende Tumor-DNA (ctDNA), welche von dem Tumor in die Blutbahn abgegeben wird, lässt sich besonders bei Virus-assoziierten Karzinomen mit hoher Spezifität nachweisen. Die Detektion der viralen Onkogene E6 und E7 bei HPV-positiven OPSCC erfolgt überwiegend mittels droplet-digital/quantitativer PCR sowie Next Generation Sequencing. Die im Blutstrom erfassbare HPV-assoziierte DNA ist bei Diagnosestellung mit dem Tumorstadium und mit dem Auftreten von lokoregionalen sowie entfernten Metastasen assoziiert. Longitudinale Untersuchungen haben weiterhin ergeben, dass nachweisbare bzw. ansteigende ctHPV-DNA-Werte im Blut im Zusammenhang mit einem Scheitern der Therapie bzw. einem Rückfall der Erkrankung stehen. Eine Standardisierung des Verfahrens ist jedoch notwendig, bevor die Liquid Biopsy endgültig Einzug in die klinische Diagnostik erhält und eine valide Reflexion das Krankheitsgeschehen ermöglichen kann.

Abstract

Human papillomavirus (HPV) is an established etiologic factor for cancers in the head and neck region, specifically for Oropharyngeal Squamous Cell Carcinoma (OPSCC). The comparatively good overall survival justifies the current discussion regarding therapy de-escalation for patients with a low-risk profile. In addition to the immunohistochemistry-based biomarker p16INK4a, there is still a need for diagnostic and prognostic biomarkers that allow risk stratification and monitoring during therapy and follow-up of these patients. In recent years, liquid biopsy, especially in the form of plasma samples, has gained importance and is already used to monitor viral DNA in patients with Epstein-Barr virus-associated nasopharyngeal carcinoma. Circulating DNA (ctDNA) released by the tumor into the bloodstream is particularly suitable for a high specificity in detecting virus-associated tumors. Detection of viral E6 and E7 oncogenes in HPV-positive OPSCC is predominantly performed by droplet digital/quantitative PCR as well as next generation sequencing. Detection of circulating HPV-DNA derived from tumor cells (ctHPV-DNA) at diagnosis is associated with advanced tumor stage, locoregional and distant metastases. Longitudinal studies have further demonstrated that detectable and/or increasing ctHPV-DNA levels are associated with treatment failure and disease relapse. However, a standardization of the diagnostic procedure is necessary before introducing liquid biopsy into the clinical routine. In the future, this might allow a valid reflection of disease progression in HPV-positive OPSCC.

Schlüsselwörter

Oropharynxkarzinom - humane Papillomaviren - Kopf-Hals-Karzinom - Liquid Biopsy - ctHPV-DNA - Biomarker - Prognose

Keywords

human papillomavirus - head and neck squamous cell carcinoma - liquid biopsy - ctHPV-DNA - biomarker - oropharyngeal squamous cell carcinoma

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