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Improved survival in HPV/p16-positive oropharyngeal cancer patients treated with postoperative radiotherapy

Verbessertes Überleben von HPV/p16-positiven Oropharynxkarzinompatienten mit postoperativer Bestrahlung

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Abstract

Introduction

In the literature, HPV infection and/or p16 positivity have been consistently demonstrated to correlate with improved response rates in oropharyngeal squamous cell carcinoma (OPSCC) patients treated with primary radiotherapy (RT) alone and in combination with chemotherapy. However, the exact role of HPV/p16 positivity in patients treated with postoperative RT is still unclear.

Methods

We analyzed tumor samples for HPV-DNA and p16 expression and correlated these variables with treatment outcome in a series of 63 consecutively treated oropharyngeal cancer patients (95 % stage III/IV). HPV and p16 analysis were performed using validated test systems. Survival was estimated by the Kaplan–Meier method. Cox proportional hazard regression models were applied to compare the risk of death among patients stratified according to risk factors.

Results

Expression of p16 or high-risk HPV-DNA was detected in 60.3 % and 39.6 % of the tumors, respectively. p16 expression [overall survival (OS) at 2 years: 91 %] as well as HPV infection (OS at 2 years: 95 %) was associated with improved OS. Mean survival in p16-positive patients was 112 months compared to 64.6 months in case of p16 negativity. All HPV-positive tumors stained positive for p16. In a multivariable analysis, p16 positivity was associated with improved OS and with disease-free survival.

Conclusion

p16 expression and HPV infection are strongly associated with the outcome of postoperatively irradiated OPSCC patients. HPV and p16 double-negative OPSCC patients should be regarded as a distinct “very high-risk patient group” that may benefit from intensified or novel treatment combinations.

Zusammenfassung

Hintergrund

In der Literatur wird sowohl die HPV-Infektion als auch eine p16-Positivität in konsistenter Weise mit besseren Ergebnissen für Patienten mit Oropharynxkarzinom (“oropharyngeal squamous cell carcinoma”, OPSCC), die eine primäre Strahlentherapie oder Radiochemotherapie erhalten haben, in Zusammenhang gebracht. Die genaue Rolle von HPV und p16-Positivität bei postoperativ bestrahlten Patienten ist jedoch nach wie vor unklar.

Methoden

Tumormaterial wurde auf HPV-DNA und p16-Expression untersucht, die Ergebnisse wurden mit den Überlebensdaten von 63 konsekutiv behandelten OPSCC-Patienten korreliert (95 % Stadium III/IV). HPV- und p16-Analysen wurden mit Hilfe von validierten Testsystemen durchgeführt. Das Überleben wurde nach der Kaplan-Meier-Methode geschätzt. Cox-Regressionsmodelle wurden für den Vergleich des Sterberisikos der nach Risikofaktoren stratifizierten Patienten verwendet.

Ergebnisse

p16-Expression oder Hochrisiko-HPV-DNA wurde in 60,3 bzw. 39,6 % der Tumoren nachgewiesen. Sowohl p16-Positivität (Gesamtüberleben nach 2 Jahren: 91 %) als auch HPV-Infektion (Gesamtüberleben nach 2 Jahren: 95 %) waren mit verbessertem Gesamtüberleben assoziiert. Das durchschnittliche Überleben bei p16-positiven Tumoren lag bei 112 Monaten, bei Patienten mit p16-negativen Tumoren bei 64,6 Monaten. Alle HPV-positiven Tumoren zeigten eine positive p16-Färbung. In einer multivariablen Analyse war p16 mit verbessertem Gesamtüberleben wie auch krankheitsfreiem Überleben assoziiert.

Schlussfolgerung

p16-Expression und HPV-Infektion sind in postoperativ bestrahlten OPSCC Patienten mit einem verbesserten Überleben assoziiert. HPV- und p16-doppelt-negative OPSCC-Patienten sollten als eine eigenständige „Sehr-hohes-Risiko-Patientengruppe“ betrachtet werden, die von intensivierten oder neuartigen Kombinationstherapien profitieren könnte.

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Conflict of interest

G. Heiduschka, A. Grah, F. Oberndorfer, L. Kadletz, G. Altorjai, G. Kornek, F. Wrba, D. Thurnher, and E. Selzer state that there are no conflicts of interest. 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).

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Authors and Affiliations

  1. Departments of Otorhinolaryngology: Head and Neck Surgery, Medical University of Vienna, Vienna, Austria

    Gregor Heiduschka M.D., Lorenz Kadletz M.D. & Dietmar Thurnher M.D.

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

    Anja Grah, Gabriela Altorjai M.D. & Edgar Selzer M.D.

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

    Felicitas Oberndorfer M.D. & Fritz Wrba M.D.

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

    Gabriela Kornek M.D.

Authors
  1. Gregor Heiduschka M.D.
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  2. Anja Grah
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  3. Felicitas Oberndorfer M.D.
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  4. Lorenz Kadletz M.D.
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  5. Gabriela Altorjai M.D.
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  6. Gabriela Kornek M.D.
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  7. Fritz Wrba M.D.
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  8. Dietmar Thurnher M.D.
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  9. Edgar Selzer M.D.
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Correspondence to Edgar Selzer M.D..

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Heiduschka, G., Grah, A., Oberndorfer, F. et al. Improved survival in HPV/p16-positive oropharyngeal cancer patients treated with postoperative radiotherapy. Strahlenther Onkol 191, 209–216 (2015). https://doi.org/10.1007/s00066-014-0753-7

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  • DOI: https://doi.org/10.1007/s00066-014-0753-7

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