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Significance of p16 expression in head and neck cancer patients treated with radiotherapy and cetuximab

Signifikanz der p16-Expression bei mit Radiotherapie und Cetuximab behandelten Patienten mit Kopf-Hals-Tumor

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Abstract

Background

HPV-infection, p16 positivity, and EGFR expression have been correlated with favorable responses of head and neck cancer patients treated with radiotherapy (RT) with or without chemotherapy. However, a possible correlation of HPV/p16 and EGFR status on the effect of RT in combination with cetuximab has not been sufficiently investigated.

Materials and methods

We analyzed tumor samples for p16 and EGFR expression and correlated these variables with treatment outcome. Cox-proportional-hazard regression models were applied to compare the risk of death among patients stratified according to risk factors. Survival was estimated by the Kaplan–Meier method. Results were compared with an institutional historical control group treated without cetuximab and with published data.

Results

Expression of p16 was predominantly found in oropharyngeal squamous cell cancer patients (OPSCC; 36.6 % positivity; 92 % of all cases), while EGFR was expressed at high levels in all tumor subsites (82 %). p16 expression was associated with improved overall survival in irradiated OPSCC patients (2-year overall survival of 80 % in p16-positive vs. 33 % overall survival in p16-negative patients). In a multivariable analysis covering all tumor sites, nodal stage (> N2a vs. ≤ N2a) and tumor site (OPSSC vs. non-OPSCC) had an impact on overall survival.

Conclusion

Our results show that p16 positivity is associated with a favorable outcome in OPSCC patients treated with RT and cetuximab.

Zusammenfassung

Hintergrund

HPV-Infektion, p16-Positivität und EGFR-Expression wurden bei Kopf-Hals-Tumorpatienten, die mit einer Strahlentherapie (RT) mit oder ohne Chemotherapie behandelt wurden, mit einem besseren Ergebnis in Verbindung gebracht. Bis jetzt wurde eine solche Korrelation bei Patienten, die mit einer RT in Kombination mit Cetuximab therapiert wurden, nicht untersucht.

Material und Methoden

Es wurden die p16- und die EGFR-Expression in Tumormaterial untersucht und die Daten mit dem Behandlungsergebnissen korreliert. Um die Sterberisiken zu vergleichen, wurden Cox-Regressionsmodelle angewendet und die Patienten nach Risikofaktoren stratifiziert. Das Überleben wurde nach der Kaplan-Mayer-Methode bewertet. Die Resultate wurden mit einer historischen Vergleichsgruppe aus unserem Institut und der Literatur verglichen.

Ergebnisse

Die p16-Expression wurde vorrangig in Oropharynxkarzinompatienten gefunden (OPSCC; 36,6 % positiv; 92 % aller positiven Fälle), während EGFR in allen Tumorlokalisationen stark exprimiert war (82 %). Die p16-Expression war in OPSCC-Patienten mit einem verbesserten Gesamtüberleben (OS) assoziiert (2-Jahres-OS von 80 % in p16-positiven vs. 33 % in p16-negativen Patienten). In einer multivariablen Analyse, die sämtliche Tumorlokalisationen umfasste, zeigten der Lymphknotenstatus (> N2a vs. ≤ N2a) und die Tumorlokalisation (OPSSC vs. non-OPSCC) einen Einfluss auf das OS.

Schlussfolgerung

Unsere Resultate zeigen, dass eine p16-Expression mit einem besseren Outcome von OPSCC-Patienten, die mit einer Kombination aus RT und Cetuximab behandelt wurden, assoziiert ist.

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Compliance with ethical guidelines

Conflict of interest

G. Heiduschka, F. Oberndorfer, R. Seemann, A. Kranz, G. Kornek, F. Wrba, and D. Thurner state that there are no conflicts of interest. E. Selzer is a recipient of a scientific grant (for basic stem cell research) from Merck Austria. The position of A. Grah is funded by a grant from Merck Austria.

All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.

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Authors and Affiliations

  1. Department of Otorhinolaryngology—Head and Neck Surgery, Medical University of Vienna, Vienna, Austria

    Gregor Heiduschka MD & Dietmar Thurnher MD

  2. Department of Radiotherapy, Medical University of Vienna, Waehringer Guertel 18–20, 1090, Vienna, Austria

    Anja Grah, Alexander Kranz MD & Edgar Selzer MD

  3. Department of Clinical Pathology, Medical University of Vienna, Vienna, Austria

    Felicitas Oberndorfer MD & Fritz Wrba MD

  4. Department of Maxillofacial Surgery, Medical University of Vienna, Vienna, Austria

    Rudolf Seemann PhD MD DMD MSc MBA

  5. Department of Medicine I—Division of Clinical Oncology, Medical University of Vienna, Vienna, Austria

    Gabriela Kornek MD

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  1. Gregor Heiduschka MD
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  2. Anja Grah
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  3. Felicitas Oberndorfer MD
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  8. Dietmar Thurnher MD
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  9. Edgar Selzer MD
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Correspondence to Edgar Selzer MD.

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Heiduschka, G., Grah, A., Oberndorfer, F. et al. Significance of p16 expression in head and neck cancer patients treated with radiotherapy and cetuximab. Strahlenther Onkol 190, 832–838 (2014). https://doi.org/10.1007/s00066-014-0652-y

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  • DOI: https://doi.org/10.1007/s00066-014-0652-y

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