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Multicenter Study
. 2018 Jun;118(12):1672-1681.
doi: 10.1038/s41416-018-0107-9. Epub 2018 May 24.

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

Christian Grønhøj  1 , David H Jensen  1 , Christian Dehlendorff  2 , Linda Marklund  3 , Steffen Wagner  4 , Hisham Mehanna  5 , Eva Munck-Wikland  3 , Torbjörn Ramqvist  3 , Anders Näsman  6 , Claus Wittekindt  4 , Nora Würdemann  4 , Shachi Jenny Sharma  4 , Stefan Gattenlöhner  7 , Katalin Kiss  8 , Elo Andersen  9 , Rachel Spruce  5 , Nikos Batis  5 , Max Robinson  10 , Kevin Harrington  11 , Stuart Winter  12 , Terence M Jones  13 , Jens Peter Klussmann  4 , Tina Dalianis  6 , Jeppe Friborg  14 , Christian von Buchwald  15
Affiliations
Multicenter Study

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

Christian Grønhøj et al. Br J Cancer. 2018 Jun.

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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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Kaplan–Meier curves depicting overall survival probability for HPV+/p16+ patients vs. HPV–/p16– patients
Fig. 2
Fig. 2
Predictive nomogram for overall survival. The nomogram is used by totalling the points identified on the top scale for each independent covariate. The total points scale is used to identify the probability of 1-, 3- and 5-year survival
Fig. 3
Fig. 3
Calibration for 1-year (top row), 3-year (middle row) and 5-year overall survival. DK Denmark (development cohort)
Fig. 4
Fig. 4
Kaplan–Meier curves depicting progression-free survival probability for HPV+/p16+ patients vs. HPV–/p16– patients
Fig. 5
Fig. 5
Predictive nomogram for progression-free survival. The nomogram is used by totalling the points identified on the top scale for each independent covariate. The total points scale is used to identify the probability of 1-, 3- and 5-year survival
Fig. 6
Fig. 6
Calibration for 1-year (top row), 3-year (middle row) and 5-year progression-free survival. DK Denmark (development cohort) (PFS progression-free survival)
See this image and copyright information in PMC

References

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