Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: a European Multicentre Study (OroGrams)

Christian Grønhøj; David H. Jensen; Christian Dehlendorff; Linda Marklund; Steffen Wagner; Hisham Mehanna; Eva Munck-Wikland; Torbjörn Ramqvist; Anders Näsman; Claus Wittekindt; Nora Würdemann; Shachi Jenny Sharma; Stefan Gattenlöhner; Katalin Kiss; Elo Andersen; Rachel Spruce; Nikolaos Batis; Max Robinson; Kevin Harrington; Stuart Winter; Terence M. Jones; Jens Peter Klussmann; Tina Dalianis; Jeppe Friborg; Christian von Buchwald

doi:10.1038/s41416-018-0107-9

Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: a European Multicentre Study (OroGrams)

Christian Grønhøj, David H. Jensen, Christian Dehlendorff, Linda Marklund, Steffen Wagner, Hisham Mehanna, Eva Munck-Wikland, Torbjörn Ramqvist, Anders Näsman, Claus Wittekindt, Nora Würdemann, Shachi Jenny Sharma, Stefan Gattenlöhner, Katalin Kiss, Elo Andersen, Rachel Spruce, Nikolaos Batis, Max Robinson, Kevin Harrington, Stuart WinterTerence M. Jones, Jens Peter Klussmann, Tina Dalianis, Jeppe Friborg, Christian von Buchwald^*

^*Corresponding author for this work

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Abstract

Background: The proxy marker for human papillomavirus (HPV), p16, is included in the new AJCC 8th/UICC 8th staging system, but due to incongruence between p16 status and HPV infection, single biomarker evaluation could lead to misallocation of patients. We established nomograms for overall survival (OS) and progression-free survival (PFS) in patients with oropharyngeal squamous cell carcinoma (OPSCC) and known HPV-DNA and p16 status, and validated the models in cohorts from high- and low-prevalent HPV countries. Methods: Consecutive OPSCC patients treated in Denmark, 2000–2014 formed the development cohort. The validation cohorts were from Sweden, Germany, and the United Kingdom. We developed nomograms by applying a backward-selection procedure for selection of variables, and assessed model performance. Results: In the development cohort, 1313 patients, and in the validation cohorts, 344 German, 503 Swedish and 463 British patients were included. For the OS nomogram, age, gender, combined HPV-DNA and p16 status, smoking, T-, N-, and M-status and UICC-8 staging were selected, and for the PFS nomogram the same variables except UICC-8 staging. The nomograms performed well in discrimination and calibration. Conclusions: Our nomograms are reliable prognostic methods in patients with OPSCC. Combining HPV DNA and p16 is essential for correct prognostication. The nomograms are available at www.orograms.org.

Original language	English
Pages (from-to)	1672-1681
Journal	British Journal of Cancer
Volume	118
DOIs	https://doi.org/10.1038/s41416-018-0107-9
Publication status	Published - 24 May 2018

Keywords

Epidemiology
Head and neck cancer

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41416-018-0107-9Licence: Creative Commons: Attribution (CC BY)

Gronhoj_et_al_Development_and_external_validation_British_Journal_of_Cancer_2018
Grønhøj, C., Jensen, D.H., Dehlendorff, C. et al. Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: a European Multicentre Study (OroGrams). Br J Cancer 118, 1672–1681 (2018). https://doi.org/10.1038/s41416-018-0107-9
Final published version, 1.35 MBLicence: Creative Commons: Attribution (CC BY)

https://doi.org/10.1038/s41416-018-0107-9Licence: Creative Commons: Attribution (CC BY)

Cite this

Grønhøj, C., Jensen, D. H., Dehlendorff, C., Marklund, L., Wagner, S., Mehanna, H., Munck-Wikland, E., Ramqvist, T., Näsman, A., Wittekindt, C., Würdemann, N., Sharma, S. J., Gattenlöhner, S., Kiss, K., Andersen, E., Spruce, R., Batis, N., Robinson, M., Harrington, K., ... von Buchwald, C. (2018). Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: a European Multicentre Study (OroGrams). British Journal of Cancer, 118, 1672-1681. https://doi.org/10.1038/s41416-018-0107-9

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title = "Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: a European Multicentre Study (OroGrams)",

abstract = "Background: The proxy marker for human papillomavirus (HPV), p16, is included in the new AJCC 8th/UICC 8th staging system, but due to incongruence between p16 status and HPV infection, single biomarker evaluation could lead to misallocation of patients. We established nomograms for overall survival (OS) and progression-free survival (PFS) in patients with oropharyngeal squamous cell carcinoma (OPSCC) and known HPV-DNA and p16 status, and validated the models in cohorts from high- and low-prevalent HPV countries. Methods: Consecutive OPSCC patients treated in Denmark, 2000–2014 formed the development cohort. The validation cohorts were from Sweden, Germany, and the United Kingdom. We developed nomograms by applying a backward-selection procedure for selection of variables, and assessed model performance. Results: In the development cohort, 1313 patients, and in the validation cohorts, 344 German, 503 Swedish and 463 British patients were included. For the OS nomogram, age, gender, combined HPV-DNA and p16 status, smoking, T-, N-, and M-status and UICC-8 staging were selected, and for the PFS nomogram the same variables except UICC-8 staging. The nomograms performed well in discrimination and calibration. Conclusions: Our nomograms are reliable prognostic methods in patients with OPSCC. Combining HPV DNA and p16 is essential for correct prognostication. The nomograms are available at www.orograms.org.",

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author = "Christian Gr{\o}nh{\o}j and Jensen, {David H.} and Christian Dehlendorff and Linda Marklund and Steffen Wagner and Hisham Mehanna and Eva Munck-Wikland and Torbj{\"o}rn Ramqvist and Anders N{\"a}sman and Claus Wittekindt and Nora W{\"u}rdemann and Sharma, {Shachi Jenny} and Stefan Gattenl{\"o}hner and Katalin Kiss and Elo Andersen and Rachel Spruce and Nikolaos Batis and Max Robinson and Kevin Harrington and Stuart Winter and Jones, {Terence M.} and Klussmann, {Jens Peter} and Tina Dalianis and Jeppe Friborg and {von Buchwald}, Christian",

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Grønhøj, C, Jensen, DH, Dehlendorff, C, Marklund, L, Wagner, S, Mehanna, H, Munck-Wikland, E, Ramqvist, T, Näsman, A, Wittekindt, C, Würdemann, N, Sharma, SJ, Gattenlöhner, S, Kiss, K, Andersen, E, Spruce, R, Batis, N, Robinson, M, Harrington, K, Winter, S, Jones, TM, Klussmann, JP, Dalianis, T, Friborg, J & von Buchwald, C 2018, 'Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: a European Multicentre Study (OroGrams)', British Journal of Cancer, vol. 118, pp. 1672-1681. https://doi.org/10.1038/s41416-018-0107-9

TY - JOUR

T1 - Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status

T2 - a European Multicentre Study (OroGrams)

AU - Grønhøj, Christian

AU - Jensen, David H.

AU - Dehlendorff, Christian

AU - Marklund, Linda

AU - Wagner, Steffen

AU - Mehanna, Hisham

AU - Munck-Wikland, Eva

AU - Ramqvist, Torbjörn

AU - Näsman, Anders

AU - Wittekindt, Claus

AU - Würdemann, Nora

AU - Sharma, Shachi Jenny

AU - Gattenlöhner, Stefan

AU - Kiss, Katalin

AU - Andersen, Elo

AU - Spruce, Rachel

AU - Batis, Nikolaos

AU - Robinson, Max

AU - Harrington, Kevin

AU - Winter, Stuart

AU - Jones, Terence M.

AU - Klussmann, Jens Peter

AU - Dalianis, Tina

AU - Friborg, Jeppe

AU - von Buchwald, Christian

PY - 2018/5/24

Y1 - 2018/5/24

N2 - Background: The proxy marker for human papillomavirus (HPV), p16, is included in the new AJCC 8th/UICC 8th staging system, but due to incongruence between p16 status and HPV infection, single biomarker evaluation could lead to misallocation of patients. We established nomograms for overall survival (OS) and progression-free survival (PFS) in patients with oropharyngeal squamous cell carcinoma (OPSCC) and known HPV-DNA and p16 status, and validated the models in cohorts from high- and low-prevalent HPV countries. Methods: Consecutive OPSCC patients treated in Denmark, 2000–2014 formed the development cohort. The validation cohorts were from Sweden, Germany, and the United Kingdom. We developed nomograms by applying a backward-selection procedure for selection of variables, and assessed model performance. Results: In the development cohort, 1313 patients, and in the validation cohorts, 344 German, 503 Swedish and 463 British patients were included. For the OS nomogram, age, gender, combined HPV-DNA and p16 status, smoking, T-, N-, and M-status and UICC-8 staging were selected, and for the PFS nomogram the same variables except UICC-8 staging. The nomograms performed well in discrimination and calibration. Conclusions: Our nomograms are reliable prognostic methods in patients with OPSCC. Combining HPV DNA and p16 is essential for correct prognostication. The nomograms are available at www.orograms.org.

AB - Background: The proxy marker for human papillomavirus (HPV), p16, is included in the new AJCC 8th/UICC 8th staging system, but due to incongruence between p16 status and HPV infection, single biomarker evaluation could lead to misallocation of patients. We established nomograms for overall survival (OS) and progression-free survival (PFS) in patients with oropharyngeal squamous cell carcinoma (OPSCC) and known HPV-DNA and p16 status, and validated the models in cohorts from high- and low-prevalent HPV countries. Methods: Consecutive OPSCC patients treated in Denmark, 2000–2014 formed the development cohort. The validation cohorts were from Sweden, Germany, and the United Kingdom. We developed nomograms by applying a backward-selection procedure for selection of variables, and assessed model performance. Results: In the development cohort, 1313 patients, and in the validation cohorts, 344 German, 503 Swedish and 463 British patients were included. For the OS nomogram, age, gender, combined HPV-DNA and p16 status, smoking, T-, N-, and M-status and UICC-8 staging were selected, and for the PFS nomogram the same variables except UICC-8 staging. The nomograms performed well in discrimination and calibration. Conclusions: Our nomograms are reliable prognostic methods in patients with OPSCC. Combining HPV DNA and p16 is essential for correct prognostication. The nomograms are available at www.orograms.org.

KW - Epidemiology

KW - Head and neck cancer

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U2 - 10.1038/s41416-018-0107-9

DO - 10.1038/s41416-018-0107-9

M3 - Article

C2 - 29795309

AN - SCOPUS:85047252879

SN - 0007-0920

VL - 118

SP - 1672

EP - 1681

JO - British Journal of Cancer

JF - British Journal of Cancer

ER -

Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: a European Multicentre Study (OroGrams)

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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