Multiple Mutations—A Genetic Marker for Extracapsular Spread in Human Papillomavirus/p16‐Positive Oropharyngeal Carcinoma

Laryngoscope Investigative Otolaryngology, vol. 10, pp. e70094

Abstract

ABSTRACT Background In the 8th edition of the TNM classification, extracapsular spread (ECS) became a factor in classifying the UICC stage of oropharyngeal carcinomas (OPSCC). We aimed to find genetic markers for ECS and to identify differences between HPV/p16‐positive and HPV/p16‐negative cases. Methods We performed targeted next‐generation sequencing on 99 samples of operable OPSCC and a retrospective analysis of clinical data. Results We included 55 HPV/p16‐positive and 44 HPV/p16‐negative patients. We found a significant difference between both groups, particularly in TP53 mutation (p < 0.001). Among other things, a small primary tumor (p < 0.001), no ECS (p = 0.026) were identified as predictors for survival. Multiple mutations were associated with an increased incidence of ECS, especially in HPV+/p16+ cases (p = 0.017). A mutation in PIK3CA occurred more frequently in nonsmokers, especially in HPV−/p16− patients (p = 0.027). A PTEN mutation—which only occurred in HPV+/p16+ tissues—reduced disease‐free survival (DFS, p = 0.026). Conclusion The presence of multiple mutations in HPV+/p16+ OPSCC was associated with a higher risk of ECS. Level of Evidence 3

Authors 10

1. Raphaela Graessle Aachen Department of Otorhinolaryngology, Head and Neck Surgery

   University of Potsdam · Medizinische Hochschule Brandenburg Theodor Fontane · Brandenburg University of Technology Cottbus-Senftenberg · RWTH Aachen University

   Affiliation as printed

   Department of Otorhinolaryngology ‐ Head and Neck Surgery RWTH Aachen University Aachen Germany

   Department of Otorhinolaryngology ‐ Head and Neck Surgery University Hospital Ruppin‐Brandenburg, Brandenburg Medical School Theodor Fontane (MHB) Neuruppin Germany

   Faculty of Health Sciences Brandenburg, Joint Faculty of the University of Potsdam Brandenburg University of Technology Cottbus‐Senftenberg and Brandenburg Medical School Potsdam Germany

   Department of Otorhinolaryngology - Head and Neck Surgery, RWTH Aachen University, Aachen, Germany

   Department of Otorhinolaryngology - Head and Neck Surgery, University Hospital Ruppin-Brandenburg, Brandenburg Medical School Theodor Fontane (MHB), Neuruppin, Germany

   Faculty of Health Sciences Brandenburg, Joint Faculty of the University of Potsdam, Brandenburg University of Technology Cottbus-Senftenberg and Brandenburg Medical School, Potsdam, Germany

2. Iris Piwonski

   Humboldt-Universität zu Berlin · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin

   Affiliation as printed

   Department of Pathology, Charité—Universitätsmedizin Berlin, Freie Universität Berlin Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin Germany

3. Cora C. Husemann

   Humboldt-Universität zu Berlin · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin

   Affiliation as printed

   Department of Pathology, Charité—Universitätsmedizin Berlin, Freie Universität Berlin Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin Germany

4. Karsten Kleo

   Humboldt-Universität zu Berlin · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin

   Affiliation as printed

   Department of Pathology, Charité—Universitätsmedizin Berlin, Freie Universität Berlin Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin Germany

5. Deema Sabtan

   Humboldt-Universität zu Berlin · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin

   Affiliation as printed

   Department of Pathology, Charité—Universitätsmedizin Berlin, Freie Universität Berlin Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin Germany

6. Achim M. Franzen

   University of Potsdam · Medizinische Hochschule Brandenburg Theodor Fontane · Brandenburg University of Technology Cottbus-Senftenberg

   Affiliation as printed

   Department of Otorhinolaryngology ‐ Head and Neck Surgery University Hospital Ruppin‐Brandenburg, Brandenburg Medical School Theodor Fontane (MHB) Neuruppin Germany

   Faculty of Health Sciences Brandenburg, Joint Faculty of the University of Potsdam Brandenburg University of Technology Cottbus‐Senftenberg and Brandenburg Medical School Potsdam Germany

   Department of Otorhinolaryngology - Head and Neck Surgery, University Hospital Ruppin-Brandenburg, Brandenburg Medical School Theodor Fontane (MHB), Neuruppin, Germany

   Faculty of Health Sciences Brandenburg, Joint Faculty of the University of Potsdam, Brandenburg University of Technology Cottbus-Senftenberg and Brandenburg Medical School, Potsdam, Germany

7. Heidi Olze

   Humboldt-Universität zu Berlin · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin

   Affiliation as printed

   Department of Otorhinolaryngology, Head and Neck Surgery, Campus Virchow Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Freie Universität Berlin Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin Germany

8. Ulrike Erben

   University of Potsdam · Brandenburg University of Technology Cottbus-Senftenberg

   Affiliation as printed

   Faculty of Health Sciences Brandenburg, Joint Faculty of the University of Potsdam Brandenburg University of Technology Cottbus‐Senftenberg and Brandenburg Medical School Potsdam Germany

   Faculty of Health Sciences Brandenburg, Joint Faculty of the University of Potsdam, Brandenburg University of Technology Cottbus-Senftenberg and Brandenburg Medical School, Potsdam, Germany

9. Michael Hummel

   Humboldt-Universität zu Berlin · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin

   Affiliation as printed

   Department of Pathology, Charité—Universitätsmedizin Berlin, Freie Universität Berlin Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin Germany

10. Annekatrin Coordes corresponding

    University of Potsdam · Medizinische Hochschule Brandenburg Theodor Fontane · Brandenburg University of Technology Cottbus-Senftenberg

    Affiliation as printed

    Department of Otorhinolaryngology ‐ Head and Neck Surgery University Hospital Ruppin‐Brandenburg, Brandenburg Medical School Theodor Fontane (MHB) Neuruppin Germany

    Faculty of Health Sciences Brandenburg, Joint Faculty of the University of Potsdam Brandenburg University of Technology Cottbus‐Senftenberg and Brandenburg Medical School Potsdam Germany

    Department of Otorhinolaryngology - Head and Neck Surgery, University Hospital Ruppin-Brandenburg, Brandenburg Medical School Theodor Fontane (MHB), Neuruppin, Germany

    Faculty of Health Sciences Brandenburg, Joint Faculty of the University of Potsdam, Brandenburg University of Technology Cottbus-Senftenberg and Brandenburg Medical School, Potsdam, Germany