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ResearchIn-Press PreviewGeneticsOncology Open Access | 10.1172/jci.insight.186680

Diagnosis of head and neck cancer by AI-based tumor-educated platelet RNA profiling of liquid biopsies

N.E. Wondergem,1 J.B. Poell,1 S.G.J.G In 't Veld,1 E. Post,1 S.W. Mes,1 M.G. Best,3 W.N. van Wieringen,1 T. Klausch,1 R.J. Baatenburg de Jong,4 C.H.J. Terhaard,5 R.P. Takes,6 J.A. Langendijk,7 I.M. Verdonck-de Leeuw,1 F. Lamers,1 C.R. Leemans,1 E. Bloemena,1 T. Würdinger,1 and R.H Brakenhoff8

1Amsterdam UMC, location VUmc, Amsterdam, Netherlands

2Amsterdam UMC, location VUmc, Netherlands

3Neurosurgery, Amsterdam UMC, Amsterdam, Netherlands

4Erasmus MC, Netherlands

5UMC Utrecht, Netherlands

6Radboud UMC, Netherlands

7Radiation Oncology, University Medical Center Groningen, Groningen, Netherlands

8Department of Otolaryngology - Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands

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1Amsterdam UMC, location VUmc, Amsterdam, Netherlands

2Amsterdam UMC, location VUmc, Netherlands

3Neurosurgery, Amsterdam UMC, Amsterdam, Netherlands

4Erasmus MC, Netherlands

5UMC Utrecht, Netherlands

6Radboud UMC, Netherlands

7Radiation Oncology, University Medical Center Groningen, Groningen, Netherlands

8Department of Otolaryngology - Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands

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1Amsterdam UMC, location VUmc, Amsterdam, Netherlands

2Amsterdam UMC, location VUmc, Netherlands

3Neurosurgery, Amsterdam UMC, Amsterdam, Netherlands

4Erasmus MC, Netherlands

5UMC Utrecht, Netherlands

6Radboud UMC, Netherlands

7Radiation Oncology, University Medical Center Groningen, Groningen, Netherlands

8Department of Otolaryngology - Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands

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1Amsterdam UMC, location VUmc, Amsterdam, Netherlands

2Amsterdam UMC, location VUmc, Netherlands

3Neurosurgery, Amsterdam UMC, Amsterdam, Netherlands

4Erasmus MC, Netherlands

5UMC Utrecht, Netherlands

6Radboud UMC, Netherlands

7Radiation Oncology, University Medical Center Groningen, Groningen, Netherlands

8Department of Otolaryngology - Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands

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1Amsterdam UMC, location VUmc, Amsterdam, Netherlands

2Amsterdam UMC, location VUmc, Netherlands

3Neurosurgery, Amsterdam UMC, Amsterdam, Netherlands

4Erasmus MC, Netherlands

5UMC Utrecht, Netherlands

6Radboud UMC, Netherlands

7Radiation Oncology, University Medical Center Groningen, Groningen, Netherlands

8Department of Otolaryngology - Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands

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1Amsterdam UMC, location VUmc, Amsterdam, Netherlands

2Amsterdam UMC, location VUmc, Netherlands

3Neurosurgery, Amsterdam UMC, Amsterdam, Netherlands

4Erasmus MC, Netherlands

5UMC Utrecht, Netherlands

6Radboud UMC, Netherlands

7Radiation Oncology, University Medical Center Groningen, Groningen, Netherlands

8Department of Otolaryngology - Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands

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1Amsterdam UMC, location VUmc, Amsterdam, Netherlands

2Amsterdam UMC, location VUmc, Netherlands

3Neurosurgery, Amsterdam UMC, Amsterdam, Netherlands

4Erasmus MC, Netherlands

5UMC Utrecht, Netherlands

6Radboud UMC, Netherlands

7Radiation Oncology, University Medical Center Groningen, Groningen, Netherlands

8Department of Otolaryngology - Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands

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1Amsterdam UMC, location VUmc, Amsterdam, Netherlands

2Amsterdam UMC, location VUmc, Netherlands

3Neurosurgery, Amsterdam UMC, Amsterdam, Netherlands

4Erasmus MC, Netherlands

5UMC Utrecht, Netherlands

6Radboud UMC, Netherlands

7Radiation Oncology, University Medical Center Groningen, Groningen, Netherlands

8Department of Otolaryngology - Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands

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1Amsterdam UMC, location VUmc, Amsterdam, Netherlands

2Amsterdam UMC, location VUmc, Netherlands

3Neurosurgery, Amsterdam UMC, Amsterdam, Netherlands

4Erasmus MC, Netherlands

5UMC Utrecht, Netherlands

6Radboud UMC, Netherlands

7Radiation Oncology, University Medical Center Groningen, Groningen, Netherlands

8Department of Otolaryngology - Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands

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1Amsterdam UMC, location VUmc, Amsterdam, Netherlands

2Amsterdam UMC, location VUmc, Netherlands

3Neurosurgery, Amsterdam UMC, Amsterdam, Netherlands

4Erasmus MC, Netherlands

5UMC Utrecht, Netherlands

6Radboud UMC, Netherlands

7Radiation Oncology, University Medical Center Groningen, Groningen, Netherlands

8Department of Otolaryngology - Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands

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1Amsterdam UMC, location VUmc, Amsterdam, Netherlands

2Amsterdam UMC, location VUmc, Netherlands

3Neurosurgery, Amsterdam UMC, Amsterdam, Netherlands

4Erasmus MC, Netherlands

5UMC Utrecht, Netherlands

6Radboud UMC, Netherlands

7Radiation Oncology, University Medical Center Groningen, Groningen, Netherlands

8Department of Otolaryngology - Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands

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1Amsterdam UMC, location VUmc, Amsterdam, Netherlands

2Amsterdam UMC, location VUmc, Netherlands

3Neurosurgery, Amsterdam UMC, Amsterdam, Netherlands

4Erasmus MC, Netherlands

5UMC Utrecht, Netherlands

6Radboud UMC, Netherlands

7Radiation Oncology, University Medical Center Groningen, Groningen, Netherlands

8Department of Otolaryngology - Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands

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1Amsterdam UMC, location VUmc, Amsterdam, Netherlands

2Amsterdam UMC, location VUmc, Netherlands

3Neurosurgery, Amsterdam UMC, Amsterdam, Netherlands

4Erasmus MC, Netherlands

5UMC Utrecht, Netherlands

6Radboud UMC, Netherlands

7Radiation Oncology, University Medical Center Groningen, Groningen, Netherlands

8Department of Otolaryngology - Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands

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1Amsterdam UMC, location VUmc, Amsterdam, Netherlands

2Amsterdam UMC, location VUmc, Netherlands

3Neurosurgery, Amsterdam UMC, Amsterdam, Netherlands

4Erasmus MC, Netherlands

5UMC Utrecht, Netherlands

6Radboud UMC, Netherlands

7Radiation Oncology, University Medical Center Groningen, Groningen, Netherlands

8Department of Otolaryngology - Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands

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1Amsterdam UMC, location VUmc, Amsterdam, Netherlands

2Amsterdam UMC, location VUmc, Netherlands

3Neurosurgery, Amsterdam UMC, Amsterdam, Netherlands

4Erasmus MC, Netherlands

5UMC Utrecht, Netherlands

6Radboud UMC, Netherlands

7Radiation Oncology, University Medical Center Groningen, Groningen, Netherlands

8Department of Otolaryngology - Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands

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1Amsterdam UMC, location VUmc, Amsterdam, Netherlands

2Amsterdam UMC, location VUmc, Netherlands

3Neurosurgery, Amsterdam UMC, Amsterdam, Netherlands

4Erasmus MC, Netherlands

5UMC Utrecht, Netherlands

6Radboud UMC, Netherlands

7Radiation Oncology, University Medical Center Groningen, Groningen, Netherlands

8Department of Otolaryngology - Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands

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1Amsterdam UMC, location VUmc, Amsterdam, Netherlands

2Amsterdam UMC, location VUmc, Netherlands

3Neurosurgery, Amsterdam UMC, Amsterdam, Netherlands

4Erasmus MC, Netherlands

5UMC Utrecht, Netherlands

6Radboud UMC, Netherlands

7Radiation Oncology, University Medical Center Groningen, Groningen, Netherlands

8Department of Otolaryngology - Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands

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1Amsterdam UMC, location VUmc, Amsterdam, Netherlands

2Amsterdam UMC, location VUmc, Netherlands

3Neurosurgery, Amsterdam UMC, Amsterdam, Netherlands

4Erasmus MC, Netherlands

5UMC Utrecht, Netherlands

6Radboud UMC, Netherlands

7Radiation Oncology, University Medical Center Groningen, Groningen, Netherlands

8Department of Otolaryngology - Head and Neck Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands

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Published November 27, 2025 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.186680.
Copyright © 2025, Wondergem et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published November 27, 2025 - Version history
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Abstract

Over 95% of head and neck cancers are squamous cell carcinoma (HNSCC). HNSCC is mostly diagnosed late, causing a poor prognosis despite the application of invasive treatment protocols. Tumor-educated platelets (TEPs) have been shown to hold promise as a molecular tool for early cancer diagnosis. We sequenced platelet mRNA isolated from blood of 101 HNSCC patients and 101 propensity-score matched non-cancer controls. Two independent machine learning classification strategies were employed using a training and validation approach to identify a cancer predictor: a particle swarm optimized support vector machine (PSO-SVM) and a least absolute shrinkage and selection operator (LASSO) logistic regression model. The best performing PSO-SVM predictor consisted of 245 platelet transcripts and reached a maximum area under the curve (AUC) of 0.87. For the LASSO-based prediction model 1,198 mRNAs were selected, resulting in an median AUC of 0.84, independent of HPV status. Our data show that TEP RNA classification by different AI tools is promising in the diagnosis of HNSCC.

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  • Version 1 (November 27, 2025): In-Press Preview
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