Strahlentherapie und Onkologie

, Volume 194, Issue 8, pp 759–770 | Cite as

Tumor volume as a prognostic marker in p16-positive and p16-negative oropharyngeal cancer patients treated with definitive intensity-modulated radiotherapy

  • Timo Carpén
  • Kauko Saarilahti
  • Caj Haglund
  • Antti Markkola
  • Jussi Tarkkanen
  • Jaana Hagström
  • Petri Mattila
  • Antti Mäkitie
Original Article



To investigate the impact of primary gross tumor volume (pGTV) and nodal gross tumor volume (nGTV) in oropharyngeal squamous cell carcinoma (OPSCC) and the difference in their role between human papillomavirus (HPV)-positive and HPV-negative patients.


The patient cohort consists of 91 OPSCC patients treated with definitive radiochemotherapy or radiotherapy using intensity-modulated radiotherapy (IMRT). All patients had a minimum follow-up of 31 months. Volume measurements were made from computer tomography (CT) scans and HPV status was assessed by p16 immunohistochemistry. The end points were as follows: overall survival (OS), disease-free survival (DFS) and locoregional control (LRC).


pGTV was a significant independent prognostic factor for overall survival (OS; p = 0.020) in p16-negative patients. nGTV of p16-negative tumors had significant prognostic value in all end points in multivariate analyses. High-stage (III–IVc) p16-negative tumors were only associated with significantly poorer OS (p = 0.046) but not with poorer LRC or DFS when compared with the low-stage (I–II) tumors. nGTV of p16-positive tumors was an independent prognostic factor for DFS (p = 0.005) and LRC (p = 0.007) in multivariate analyses.


pGTV may serve as an independent prognostic factor in p16-negative patients and nGTV may serve as an independent prognostic factor both in p16-positive and p16-negative patients treated with radiochemotherapy or radiotherapy using IMRT. Tumor volume may have an impact on selecting patients for de-escalation protocols in the future, both in p16-positive and p16-negative patients.


Human papillomavirus Survival Oncology Radiochemotherapy Marker 

Tumorvolumen als prognostischer Marker bei p16-positiven und p16-negativen Patienten mit Oropharyngealkarzinom unter Therapie mit definitiver intensitätsmodulierter Strahlentherapie



Ziel war es, die Bedeutung des makroskopischen Tumorvolumens des Primärtumors („primary gross tumor volume“, pGTV) und des makroskopischen Tumorvolumens der Lymphknoten („nodal gross tumor volume“, nGTV) bei Plattenepithelkarzinomen des Oropharynx („oropharyngeal squamous cell carcinoma“, OPSCC) und deren Unterschiede zwischen für humanes Papillomavirus (HPV) positiven und HPV-negativen Patienten zu untersuchten.


In die Studie eingeschlossen wurden 91 OPSCC-Patienten, die mit definitiver intensitätsmodulierter Strahlentherapie („intensity-modulated radiotherapy“, IMRT) mit oder ohne gleichzeitige Chemotherapie behandelt wurden. Bei allen Patienten betrug der Nachbeobachtungszeitraum mindestens 31 Monate. Die Volumenmessungen erfolgten anhand von Computertomographie(CT)-Aufnahmen. Der HPV-Status wurde durch die p16-Immunhistochemie ermittelt. Die Endpunkte waren Gesamtüberleben („overall survival“, OS), krankheitsfreies Überleben („disease-free survival“, DFS) und lokoregionale Kontrolle („locoregional control“, LRC).


Das pGTV war ein signifikanter unabhängiger prognostischer Faktor für das OS (p = 0,20) bei p16-negativen Patienten. Das nGTV von p16-negativen Tumoren wies einen signifikanten prognostischen Wert für alle Endpunkte in multivariaten Analysen auf. p16-negative Tumoren in hohen Stadien (III-IVc) waren im Vergleich zu den Tumoren in niedrigeren Stadien (I‑II) nur mit einem signifikant schlechteren OS (p = 0,046), nicht aber mit schlechteren Werten für LRC oder DFS assoziiert. Das nGTV von p16-negativen Tumoren erwies sich in multivariaten Analysen als unabhängiger prognostischer Faktor für DFS (p = 0,005) und LRC (p = 0,007).


Das pGTV kann als unabhängiger prognostischer Faktor bei p16-negativen Patienten und das nGTV als unabhängiger prognostischer Faktor sowohl bei p16-positiven als auch bei p16-negativen Patienten dienen, bei denen eine Radiochemotherapie oder Strahlentherapie unter Verwendung der IMRT erfolgt. Das Tumorvolumen kann bei der Auswahl der Patienten für ein Deeskalationsprotokoll sowohl bei p16-positiven als auch bei p16-negativen Patienten eine Rolle spielen.


Humanes Papillomavirus Überleben Onkologie Radiochemotherapie Marker 



This study was supported by grants from the Helsinki University Hospital Research Fund and the Finska Läkaresällskapet.

Compliance with ethical guidelines

Conflict of interest

T. Carpén, K. Saarilahti, C. Haglund, A. Markkola, J. Tarkkanen, J. Hagström, P. Mattila, and A. Mäkitie declare that they have no competing interests.

Ethical standards

This article does not contain any studies with human participants or animals performed by any of the authors. Consent was obtained from all patients identifiable from images or other information within the manuscript. In the case of underage patients, consent was obtained from a parent or legal guardian.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Timo Carpén
    • 1
  • Kauko Saarilahti
    • 2
  • Caj Haglund
    • 3
    • 4
  • Antti Markkola
    • 5
  • Jussi Tarkkanen
    • 6
  • Jaana Hagström
    • 4
    • 6
  • Petri Mattila
    • 1
  • Antti Mäkitie
    • 1
    • 7
  1. 1.Department of Otorhinolaryngology—Head and Neck SurgeryUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
  2. 2.Department of OncologyUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
  3. 3.Department of SurgeryUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
  4. 4.Research Program Unit, Translational Cancer BiologyUniversity of HelsinkiHelsinkiFinland
  5. 5.Department of RadiologyUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
  6. 6.Department of Pathology, Haartman Institute and HUSLABUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
  7. 7.Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and TechnologyKarolinska Institutet and Karolinska HospitalStockholmSweden

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