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Humane Papillomviren bei Plattenepithelkarzinomen der Kopf- und Halsregion

Relevanz für Prognose, Therapie und Prophylaxe

Human papillomavirus and squamous cell cancer of the head and neck region

Prognostic, therapeutic and prophylactic implications

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Zusammenfassung

Humane Papillomviren (HPV) verursachen bereits etwa die Hälfte aller Oropharynxkarzinome („oropharyngeal squamous cell carcinoma“, OPSCC) und die Neuerkrankungsrate HPV-assoziierter OPSCC steigt weiter stark an. Die virale Ursache ermöglicht die Entwicklung spezifischer diagnostischer, therapeutischer und prophylaktischer Verfahren. Die labortechnische Identifizierung eines HPV-assoziierten OPSCC kann durch die p16INK4a-Immunhistologie kombiniert mit einem HPV-DNA-Nachweis mittels Polymerasekettenreaktion (PCR) aus Tumorgewebe erfolgen. Patienten mit HPV-assoziierten OPSCC haben eine relativ gute Prognose, daher spielt die Feststellung der HPV-Assoziation in der Patientenberatung eine wichtige Rolle. Aufgrund der relativ günstigen Prognose wird in laufenden Studien geprüft, ob mit einer weniger intensiven Therapie für HPV-positive Patienten gleiche Heilungsraten erreicht werden können. Die Kriterien für eine Selektion geeigneter Patienten sind allerdings noch unklar. Insbesondere fehlen bisher Marker zur Erkennung HPV-positiver Patienten mit hohem Risiko für Therapieversagen. Neben dem Tumorstadium und der Komorbidität sind bei HPV-assoziierten OSPCC bestimmte genomische, epigenetische und immunologische Veränderungen prognostisch relevant und könnten einen prädiktiven Nutzen haben. Die charakteristischen Veränderungen auf molekularer Ebene lassen zudem neue schonendere und spezifischere Therapieansätze möglich erscheinen. Hierzu gehören Inhibitoren des bei HPV-assoziierten OPSCC häufig aktivierten Phosphatidylinositol-3-Kinase(PI3K)-Signalwegs sowie immuntherapeutische Verfahren, z. B. die therapeutische Impfung. Obwohl die prophylaktische HPV-Impfung auch die Entstehung HPV-assoziierter OPSCC verhindern kann, wird der Effekt auf die Inzidenz von OPSCC mit den in Deutschland niedrigen Impfraten in absehbarer Zeit gering sein. Dies verdeutlicht, dass interdisziplinäre Forschungsnetzwerke die notwendige Aktivität zu HPV-assoziierten OPSCC verstärkt sicherstellen sollten.

Abstract

Human papilloma viruses (HPV) are responsible for approximately half of all oropharyngeal squamous cell carcinomas (OPSCC) and incidence rates of HPV-associated OPSCC continue to increase substantially. The defined viral carcinogenesis permits development of specific diagnostic, therapeutic, and prophylactic approaches. Laboratory identification of HPV-associated OPSCC may be achieved by p16INK4a immunohistochemistry combined with HPV DNA detection by polymerase chain reaction (PCR) using tumor tissue. Patients with HPV-associated OPSCC have a relatively good prognosis; therefore, the HPV status plays an important role in patient guidance. Due to the relatively favorable prognosis, ongoing studies are evaluating whether less rigorous therapy for HPV-positive patients results in equally good cure rates. The criteria for patient selection are, however, still uncertain. Particularly markers for detection of HPV-positive patients with a high risk of treatment failure are lacking. Besides tumor stage and comorbidities, distinct genomic, epigenetic, and immunologic alterations are prognostically relevant for HPV-associated OPSCC, and might be of predictive value. Furthermore, the characteristic molecular alterations suggest the possibility of novel vigilant and specific therapy approaches. These may be inhibitors of the phosphatidylinositol 3‑kinase (PI3K) pathway, which is frequently activated in HPV-associated OPSCC, and immunotherapeutic methods, e. g., therapeutic vaccination. Although prophylactic HPV vaccinations may also prevent development of HPV-associated OPSCC, foreseeable effects on OPSCC incidence will be low, given the low vaccination rates in Germany. This highlights the fact that interdisciplinary research networks should enhance the necessary activities related to HPV-associated OPSCC.

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Authors and Affiliations

  1. Abteilung für Angewandte Tumorbiologie, Institut für Pathologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Deutschland

    M. Reuschenbach, E.‑S. Prigge, M. Sauer & M. von Knebel Doeberitz

  2. The Human Papillomavirus Infection and Oropharyngeal Cancer Consortium (HOCC) http://hocc.com

    M. Reuschenbach, S. Wagner, N. Würdemann, S. J. Sharma, E.‑S. Prigge, M. Sauer, A. Wittig, C. Wittekindt, M. von Knebel Doeberitz & J. P. Klussmann

  3. Klinik für HNO-Heilkunde, Kopf-, Halschirurgie, Universitätsklinikum Gießen, Justus-Liebig-Universität Gießen, Gießen, Deutschland

    S. Wagner, N. Würdemann, S. J. Sharma, C. Wittekindt & J. P. Klussmann

  4. Klinik für Strahlentherapie und Radioonkologie, Universitätsklinikum Gießen und Marburg, Philipps-Universität Marburg, Marburg, Deutschland

    A. Wittig

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  1. M. Reuschenbach
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  2. S. Wagner
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Interessenkonflikt

S. Wagner, N. Würdemann, S. J. Sharma, M. Sauer, A. Wittig, C. Wittekindt und J. P. Klussmann geben an, dass kein Interessenkonflikt besteht.

M. von Knebel Doeberitz gibt Zuschüsse und persönliche Honorare der Fa. Oryx GmbH und Co. KG an; außerdem ist M. von Knebel Doeberitz als Erfinder auf einem Patent zu p16ink4a abstammenden Peptiden zur Prophylaxe und Therapie HPV-assoziierter Tumoren und anderer p16ink4a exprimierender Tumoren gelistet, und ihm wurde ein Patent auf die individuelle Immunisierung gegen Karzinome und ihre Vorstufen erteilt.

E.-S. Prigge gibt Zuschüsse der Fa. Oryx GmbH & Co. KG an das Universitätsklinikum Heidelberg an.

M. Reuschenbach gibt Zuschüsse der Fa. Oryx GmbH & Co. KG an das Universitätsklinikum Heidelberg an; darüber hinaus ist M. Reuschenbach als Erfinderin auf einem Patent zu p16 abstammenden Peptiden zur Prophylaxe und Therapie HPV-assoziierter Tumoren und anderer p16 exprimierender Tumoren gelistet.

Dieser Beitrag beinhaltet keine Originaldaten aus Studien an Menschen oder Tieren.

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Reuschenbach, M., Wagner, S., Würdemann, N. et al. Humane Papillomviren bei Plattenepithelkarzinomen der Kopf- und Halsregion. HNO 64, 450–459 (2016). https://doi.org/10.1007/s00106-016-0123-0

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