PET/CT radiomics signature of human papilloma virus association in oropharyngeal squamous cell carcinoma

Eur J Nucl Med Mol Imaging. 2020 Dec;47(13):2978-2991. doi: 10.1007/s00259-020-04839-2. Epub 2020 May 12.


Purpose: To devise, validate, and externally test PET/CT radiomics signatures for human papillomavirus (HPV) association in primary tumors and metastatic cervical lymph nodes of oropharyngeal squamous cell carcinoma (OPSCC).

Methods: We analyzed 435 primary tumors (326 for training, 109 for validation) and 741 metastatic cervical lymph nodes (518 for training, 223 for validation) using FDG-PET and non-contrast CT from a multi-institutional and multi-national cohort. Utilizing 1037 radiomics features per imaging modality and per lesion, we trained, optimized, and independently validated machine-learning classifiers for prediction of HPV association in primary tumors, lymph nodes, and combined "virtual" volumes of interest (VOI). PET-based models were additionally validated in an external cohort.

Results: Single-modality PET and CT final models yielded similar classification performance without significant difference in independent validation; however, models combining PET and CT features outperformed single-modality PET- or CT-based models, with receiver operating characteristic area under the curve (AUC) of 0.78, and 0.77 for prediction of HPV association using primary tumor lesion features, in cross-validation and independent validation, respectively. In the external PET-only validation dataset, final models achieved an AUC of 0.83 for a virtual VOI combining primary tumor and lymph nodes, and an AUC of 0.73 for a virtual VOI combining all lymph nodes.

Conclusion: We found that PET-based radiomics signatures yielded similar classification performance to CT-based models, with potential added value from combining PET- and CT-based radiomics for prediction of HPV status. While our results are promising, radiomics signatures may not yet substitute tissue sampling for clinical decision-making.

Keywords: HPV; Imaging biomarker; Oropharyngeal squamous cell carcinoma; PET/CT; Quantitative imaging; Radiomics.

MeSH terms

  • Alphapapillomavirus*
  • Head and Neck Neoplasms*
  • Humans
  • Papillomaviridae
  • Positron Emission Tomography Computed Tomography
  • Retrospective Studies
  • Squamous Cell Carcinoma of Head and Neck