Integration of p16/HPV DNA Status with a 24-miRNA-Defined Molecular Phenotype Improves Clinically Relevant Stratification of Head and Neck Cancer Patients

Hess J, Unger K, Maihoefer C, Schuettrumpf L, Weber P, Marschner S, Wintergerst L, Pflugradt U, Baumeister P, Walch A, Woischke C, Kirchner T, Werner M, Soerensen K, Baumann M, Tinhofer I, Combs SE, Debus J, Schäfer H, Krause M, Linge A, von der Grün J, Stuschke M, Zips D, Canis M, Lauber K, Ganswindt U, Henke M, Zitzelsberger H, Belka C (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Cancers MDPI

Book Volume: 14

Article Number: 3745

Journal Issue: 15

DOI: 10.3390/cancers14153745

Abstract

Human papillomavirus (HPV)-driven head and neck squamous cell carcinomas (HNSCC) generally have a more favourable prognosis. We hypothesized that HPV-associated HNSCC may be identified by an miRNA-signature according to their specific molecular pathogenesis, and be characterized by a unique transcriptome compared to HPV-negative HNSCC. We performed miRNA expression profiling of two p16/HPV DNA characterized HNSCC cohorts of patients treated by adjuvant radio(chemo)therapy (multicentre DKTK-ROG n = 128, single-centre LMU-KKG n = 101). A linear model predicting HPV status built in DKTK-ROG using lasso-regression was tested in LMU-KKG. LMU-KKG tumours (n = 30) were transcriptome profiled for differential gene expression and miRNA-integration. A 24-miRNA signature predicted HPV-status with 94.53% accuracy (AUC: 0.99) in DKTK-ROG, and 86.14% (AUC: 0.86) in LMU-KKG. The prognostic values of 24-miRNA- and p16/HPV DNA status were comparable. Combining p16/HPV DNA and 24-miRNA status allowed patient sub-stratification and identification of an HPV-associated patient subgroup with impaired overall survival. HPV-positive tumours showed downregulated MAPK, Estrogen, EGFR, TGFbeta, WNT signaling activity. miRNA-mRNA integration revealed HPV-specific signaling pathway regulation, including PD−L1 expression/PD−1 checkpoint pathway in cancer in HPV-associated HNSCC. Integration of clinically established p16/HPV DNA with 24-miRNA signature status improved clinically relevant risk stratification, which might be considered for future clinical decision-making with respect to treatment de-escalation in HPV-associated HNSCC.

Involved external institutions

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Ruprecht-Karls-Universität Heidelberg DE Germany (DE)

How to cite

APA:

Hess, J., Unger, K., Maihoefer, C., Schuettrumpf, L., Weber, P., Marschner, S.,... Belka, C. (2022). Integration of p16/HPV DNA Status with a 24-miRNA-Defined Molecular Phenotype Improves Clinically Relevant Stratification of Head and Neck Cancer Patients. Cancers, 14(15). https://doi.org/10.3390/cancers14153745

MLA:

Hess, Julia, et al. "Integration of p16/HPV DNA Status with a 24-miRNA-Defined Molecular Phenotype Improves Clinically Relevant Stratification of Head and Neck Cancer Patients." Cancers 14.15 (2022).

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