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Deep learning predicts HPV association in oropharyngeal squamous cell carcinomas and identifies patients with a favorable prognosis using regular H&E stains

Purpose: Human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC) is tumorigenic and has been associated with a favorable prognosis compared with OPSCC caused by tobacco, alcohol, and other carcinogens. Meanwhile, machine learning has evolved as a powerful tool to predict molecula...

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Main Authors: Klein, Sebastian (Author) , Quaas, Alexander (Author) , Quantius, Jennifer (Author) , Löser, Heike (Author) , Meinel, Jörn (Author) , Peifer, Martin (Author) , Wagner, Steffen (Author) , Gattenlöhner, Stefan (Author) , Wittekindt, Claus (Author) , Knebel Doeberitz, Magnus von (Author) , Prigge, Elena-Sophie (Author) , Langer, Christine (Author) , Noh, Ka-Won (Author) , Maltseva, Margaret (Author) , Reinhardt, Christian (Author) , Büttner, Reinhard (Author) , Klußmann, Jens Peter (Author) , Würdemann, Nora (Author)
Format: Article (Journal)
Language:English
Published: February 2021
In: Clinical cancer research
Year: 2021, Volume: 27, Issue: 4, Pages: 1131-1138
ISSN:1557-3265
DOI:10.1158/1078-0432.CCR-20-3596
Online Access:Verlag, lizenzpflichtig, Volltext: https://clincancerres.aacrjournals.org/content/27/4/1131
Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1158/1078-0432.CCR-20-3596
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Author Notes:Sebastian Klein, Alexander Quaas, Jennifer Quantius, Heike Löser, Martin Peifer, Steffen Wagner, Stefan Gattenlöhner, Claus Wittekindt, Magnus von Knebel Doeberitz, Elena-Sophie Prigge, Christine Langer, Ka-Won Noh, Margaret Maltseva, Hans Christian Reinhardt, Reinhard Büttner, Jens Peter Klussmann, Nora Wuerdemann
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Summary:Purpose: Human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC) is tumorigenic and has been associated with a favorable prognosis compared with OPSCC caused by tobacco, alcohol, and other carcinogens. Meanwhile, machine learning has evolved as a powerful tool to predict molecular and cellular alterations of medical images of various sources. - Experimental Design: We generated a deep learning-based HPV prediction score (HPV-ps) on regular hematoxylin and eosin (H&E) stains and assessed its performance to predict HPV association using 273 patients from two different sites (OPSCC; Giessen, n = 163; Cologne, n = 110). Then, the prognostic relevance in a total of 594 patients (Giessen, Cologne, HNSCC TCGA) was evaluated. In addition, we investigated whether four board-certified pathologists could identify HPV association (n = 152) and compared the results to the classifier. - Results: Although pathologists were able to diagnose HPV association from H&E-stained slides (AUC = 0.74, median of four observers), the interrater reliability was minimal (Light Kappa = 0.37; P = 0.129), as compared with AUC = 0.8 using the HPV-ps within two independent cohorts (n = 273). The HPV-ps identified individuals with a favorable prognosis in a total of 594 patients from three cohorts (Giessen, OPSCC, HR = 0.55, P < 0.0001; Cologne, OPSCC, HR = 0.44, P = 0.0027; TCGA, non-OPSCC head and neck, HR = 0.69, P = 0.0073). Interestingly, the HPV-ps further stratified patients when combined with p16 status (Giessen, HR = 0.06, P < 0.0001; Cologne, HR = 0.3, P = 0.046). - Conclusions: Detection of HPV association in OPSCC using deep learning with help of regular H&E stains may either be used as a single biomarker, or in combination with p16 status, to identify patients with OPSCC with a favorable prognosis, potentially outperforming combined HPV-DNA/p16 status as a biomarker for patient stratification.
Item Description:Gesehen am 23.11.2021
Physical Description:Online Resource
ISSN:1557-3265
DOI:10.1158/1078-0432.CCR-20-3596

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