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

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: Molecular Diagnostics

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 LükewilleChristiane Maria Stuhlmann-Laeisz, Christoph Röcken, Carolin Mogler, Jan Budczies, Melanie Boxberg^*

^*Corresponding author for this work

3 Citations (Scopus)

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.

Original language	English
Article number	524928
Journal	British Journal of Cancer
Volume	132
Issue number	2
Pages (from-to)	212-221
Number of pages	10
ISSN	0007-0920
DOIs	https://doi.org/10.1038/s41416-024-02912-3
Publication status	Published - 10.02.2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Research Area: Luebeck Integrated Oncology Network (LION)
Centers: University Cancer Center Schleswig-Holstein (UCCSH)

DFG Research Classification Scheme

2.22-06 Pathology
2.22-14 Hematology, Oncology

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10.1038/s41416-024-02912-3

Cite this

Stögbauer, F., Wirth, M., Lauterbach, M., Wollenberg, B., Schmidl, B., Hoch, C. C., Ourailidis, I., Hess, J., Eckstein, M., Hartmann, A., Iro, H., Gostian, A. O., Balk, M., Jesinghaus, M., Ribbat-Idel, J., Sailer, V. W., Perner, S., Bruchhage, K. L., Hoffmann, M., ... Boxberg, M. (2025). Tumor budding and lymphovascular invasion as prognostic factors in p16-positive oropharyngeal squamous cell carcinomas: Molecular Diagnostics. British Journal of Cancer, 132(2), 212-221. Article 524928. https://doi.org/10.1038/s41416-024-02912-3

@article{fbabc2f6f08e4192baa428302a212b64,

title = "Tumor budding and lymphovascular invasion as prognostic factors in p16-positive oropharyngeal squamous cell carcinomas: Molecular Diagnostics",

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.",

author = "Fabian St{\"o}gbauer and Markus Wirth and Maren Lauterbach and Barbara Wollenberg and Benedikt Schmidl and Hoch, \{Cosima C.\} and Iordanis Ourailidis and Jochen Hess and Markus Eckstein and Arndt Hartmann and Heinrich Iro and Gostian, \{Antoniu Oreste\} and Matthias Balk and Moritz Jesinghaus and Julika Ribbat-Idel and Sailer, \{Verena Wilbeth\} and Sven Perner and Bruchhage, \{Karl Ludwig\} and Markus Hoffmann and Lukas L{\"u}kewille and Stuhlmann-Laeisz, \{Christiane Maria\} and Christoph R{\"o}cken and Carolin Mogler and Jan Budczies and Melanie Boxberg",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2025",

month = feb,

day = "10",

doi = "10.1038/s41416-024-02912-3",

language = "English",

volume = "132",

pages = "212--221",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Springer Nature",

number = "2",

}

Stögbauer, F, Wirth, M, Lauterbach, M, Wollenberg, B, Schmidl, B, Hoch, CC, Ourailidis, I, Hess, J, Eckstein, M, Hartmann, A, Iro, H, Gostian, AO, Balk, M, Jesinghaus, M, Ribbat-Idel, J, Sailer, VW, Perner, S, Bruchhage, KL, Hoffmann, M, Lükewille, L, Stuhlmann-Laeisz, CM, Röcken, C, Mogler, C, Budczies, J & Boxberg, M 2025, 'Tumor budding and lymphovascular invasion as prognostic factors in p16-positive oropharyngeal squamous cell carcinomas: Molecular Diagnostics', British Journal of Cancer, vol. 132, no. 2, 524928, pp. 212-221. https://doi.org/10.1038/s41416-024-02912-3

TY - JOUR

T1 - Tumor budding and lymphovascular invasion as prognostic factors in p16-positive oropharyngeal squamous cell carcinomas

T2 - Molecular Diagnostics

AU - Stögbauer, Fabian

AU - Wirth, Markus

AU - Lauterbach, Maren

AU - Wollenberg, Barbara

AU - Schmidl, Benedikt

AU - Hoch, Cosima C.

AU - Ourailidis, Iordanis

AU - Hess, Jochen

AU - Eckstein, Markus

AU - Hartmann, Arndt

AU - Iro, Heinrich

AU - Gostian, Antoniu Oreste

AU - Balk, Matthias

AU - Jesinghaus, Moritz

AU - Ribbat-Idel, Julika

AU - Sailer, Verena Wilbeth

AU - Perner, Sven

AU - Bruchhage, Karl Ludwig

AU - Hoffmann, Markus

AU - Lükewille, Lukas

AU - Stuhlmann-Laeisz, Christiane Maria

AU - Röcken, Christoph

AU - Mogler, Carolin

AU - Budczies, Jan

AU - Boxberg, Melanie

PY - 2025/2/10

Y1 - 2025/2/10

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85210552318

UR - https://www.mendeley.com/catalogue/ef1f1a42-b529-3e14-826f-226a016db49b/

U2 - 10.1038/s41416-024-02912-3

DO - 10.1038/s41416-024-02912-3

M3 - Journal articles

C2 - 39613843

AN - SCOPUS:85210552318

SN - 0007-0920

VL - 132

SP - 212

EP - 221

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 2

M1 - 524928

ER -

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

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