Tumor budding and lymphovascular invasion as prognostic factors in p16-positive oropharyngeal squamous cell carcinomas

Fabian Stögbauer; Markus Wirth; Maren Lauterbach; Barbara Wollenberg; Benedikt Schmidl; Cosima C Hoch; Iordanis Ourailidis; Jochen Hess; Markus Eckstein; Arndt Hartmann; Heinrich Iro; Antoniu-Oreste Gostian; Matthias Balk; Moritz Jesinghaus; Julika Ribbat-Idel; Verena-Wilbeth Sailer; Sven Perner; Karl-Ludwig Bruchhage; Markus Hoffmann; Lukas Lükewille; Christiane Maria Stuhlmann-Laeisz; Christoph Röcken; Carolin Mogler; Jan Budczies; Melanie Boxberg

doi:10.1038/s41416-024-02912-3

Tumor budding and lymphovascular invasion as prognostic factors in p16-positive oropharyngeal squamous cell carcinomas

Br J Cancer. 2024 Nov 29. doi: 10.1038/s41416-024-02912-3. Online ahead of print.

Authors

Fabian Stögbauer¹, Markus Wirth², Maren Lauterbach², Barbara Wollenberg², Benedikt Schmidl², Cosima C Hoch², Iordanis Ourailidis³, Jochen Hess⁴, Markus Eckstein^{5

6

7}, Arndt Hartmann^{5

6

7}, Heinrich Iro^{6

8}, Antoniu-Oreste Gostian^{6

8

9}, Matthias Balk^{6

8}, Moritz Jesinghaus¹⁰, Julika Ribbat-Idel¹¹, Verena-Wilbeth Sailer^{12

13}, Sven Perner¹⁴, Karl-Ludwig Bruchhage¹⁵, Markus Hoffmann¹⁶, Lukas Lükewille¹⁶, Christiane Maria Stuhlmann-Laeisz¹⁷, Christoph Röcken¹⁷, Carolin Mogler¹⁸, Jan Budczies^#³, Melanie Boxberg^#¹⁹

Affiliations

¹ Technical University of Munich, TUM School of Medicine and Health, Institute of General and Surgical Pathology, Munich, Germany. fabian.stoegbauer@tum.de.
² Department of Otolaryngology, Head and Neck Surgery, School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany.
³ University of Heidelberg, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
⁴ Department of Otorhinolaryngology, Head and Neck Surgery, Experimental Head and Neck Oncology, Heidelberg University Hospital, Heidelberg, Germany.
⁵ Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
⁶ Bavarian Cancer Research Center (Bayerisches Zentrum für Krebsforschung, BZKF), Erlangen, Germany.
⁷ Comprehensive Cancer Center EMN, University Hospital Erlangen, Friedrich- Alexander- Universität Erlangen- Nürnberg, Erlangen, Germany.
⁸ Department of Otolaryngology, Head & Neck Surgery, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
⁹ Department of Otorhinolaryngology, Merciful Brothers Hospital St. Elisabeth, Straubing, Germany.
¹⁰ Institute of Pathology, University Hospital Marburg, Marburg, Germany.
¹¹ Institute of Pathology, University of Lübeck, Lübeck, Germany.
¹² Pathology of the University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
¹³ Pathology, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
¹⁴ Center for Precision Oncology Tübingen, Tübingen, Germany.
¹⁵ Department of Otorhinolaryngology, University of Luebeck, Luebeck, Germany.
¹⁶ Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University Kiel, Kiel, Germany.
¹⁷ Department for Pathology, Christian-Albrechts-University of Kiel, Kiel, Germany.
¹⁸ Technical University of Munich, TUM School of Medicine and Health, Institute of General and Surgical Pathology, Munich, Germany.
¹⁹ Technical University of Munich, TUM School of Medicine and Health, Institute of General and Surgical Pathology, Munich, Germany. melanie.boxberg@tum.de.

^# Contributed equally.

PMID: 39613843
DOI: 10.1038/s41416-024-02912-3

Abstract

Background: We aimed to validate the prognostic significance of tumor budding (TB) in p16-positive oropharyngeal squamous cell carcinomas (OPSCC).

Methods: We analyzed digitized H&E-stained slides from a multicenter cohort of five large university centers consisting of n = 275 cases of p16-positive OPSCC. We evaluated TB along with other histological parameters (morphology, tumor-stroma-ratio, lymphovascular invasion (LVI), perineural invasion) and calculated survival outcomes using both univariate and multivariate analyses.

Results: TB was identified as an independent prognostic parameter, with TB-high cases showing inferior outcomes in univariate (HR: 3.08, 95%-CI: 1.71-5.54) and multivariate analyses (HR: 4.03, 95%-CI: 1.65-9.83). Similarly, LVI remained an independent prognostic factor (HR: 3.00, 95%-CI: 1.22-7.38). A combined classification including TB and LVI stratified cases into low-, intermediate- and high-risk categories. We could not detect correlations between TB and the number of lymph node metastases or between TB and an extracapsular extension of lymph node metastases.

Conclusions: In addition to LVI, we could identify TB as an independent prognostic factor in p16-positive OPSCC in this multicenter study cohort. Thus, evaluating TB along with LVI in a combined scheme for prognostication might help to establish a more personalized treatment regimen for patients with p16-positive OPSCC.