Development and validation of a radiomic signature to predict HPV (p16) status from standard CT imaging: a multicenter study

Ralph T. H. Leijenaar*, Marta Bogowicz, Arthur Jochems, Frank J. P. Hoebers, Frederik W. R. Wesseling, Sophie H. Huang, Biu Chan, John N. Waldron, Brian O'Sullivan, Derek Rietveld, C. Rene Leemans, Ruud H. Brakenhoff, Oliver Riesterer, Stephanie Tanadini-Lang, Matthias Guckenberger, Kristian Ikenberg, Philippe Lambin

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Objectives: Human papillomavirus (HPV) positive oropharyngeal cancer (oropharyngeal squamous cell carcinoma, OPSCC) is biologically and clinically different from HPV negative OPSCC. Here, we evaluate the use of a radiomic approach to identify the HPV status of OPSCC. Methods: Four independent cohorts, totaling 778 OPSCC patients with HPV determined by p16 were collected. We randomly assigned 80% of all data for model training (N = 628) and 20% for validation (N = 150). On the pre-treatment CT images, 902 radiomic features were calculated from the gross tumor volume. Multivariable modeling was performed using least absolute shrinkage and selection operator. To assess the impact of CT artifacts in predicting HPV (p16), a model was developed on all training data (M-all) and on the artifact-free subset of training data (M-no (art)), Models were validated on all validation data (V-all), and the subgroups with (V-art) and without (V-no (art)) artifacts. Kaplan-Meier survival analysis was performed to compare HPV status based on p16 and radiomic model predictions. Results: The area under the receiver operator curve for M-all and M-no (art) ranged between 0.70 and 0.80 and was not significantly different for all validation data sets. There was a consistent and significant split between survival curves with HPV status determined by p16 [p = 0.007; hazard ratio (HR): 0.46], M-all (p = 0.036; HR: 0.55) and M-no (art) (P = 0.027; HR: 0.49). Conclusion: This study provides proof of concept that molecular information can be derived from standard medical images and shows potential for radiomics as imaging biomarker of HPV status. Advances in knowledge: Radiomics has the potential to identify clinically relevant molecular phenotypes.
Original languageEnglish
Article number2017049811075
Number of pages8
JournalBritish Journal of Radiology
Issue number1086
Publication statusPublished - 1 Jan 2018


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