Prognostic Significance of Tumor–Stroma Ratio (TSR) in Head and Neck Squamous Cell Carcinoma - Systematic Review and Meta-Analysis

Q: How does the tumor–stroma ratio (TSR) relate tumor tissue to stromal tissue?

TSR quantifies the proportion of tumor tissue compared with the surrounding stroma by assessing the percentage of stromal tissue within the tumor area. A 50% cutoff is commonly used to distinguish higher-stroma from lower-stroma groups.

Q: What did the review find about TSR and overall survival in HNSCC?

TSR showed a significant association with overall survival in both unadjusted and adjusted analyses, with stronger prognostic potential reported for oral cavity/oral tongue cancers.

Q: How can TSR be evaluated in routine histology practice?

TSR can be assessed on routine hematoxylin and eosin-stained slides by selecting fields that include tumor invasion fronts with the highest stroma content and evaluating areas containing both stroma and tumor while excluding necrosis and major vascular or muscle tissue.

Sep 21, 2026

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The management of head and neck squamous cell carcinoma (HNSCC) depends largely on TNM staging and WHO histologic grading, yet prognostic markers in the tumor stroma have become increasingly important. The tumor–stroma ratio (TSR) measures the proportion of tumor tissue relative to surrounding stromal tissue, typically using a 50% cutoff. This systematic review and meta-analysis evaluates TSR as a prognostic factor and includes 24 studies reporting survival outcomes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Abstract

Introduction

Background on HNSCC and staging limitations

Rationale for stromal prognostic markers

Definition and assessment of TSR

Keywords

cells Systematic Review Prognostic Significance of Tumor–Stroma Ratio (TSR) in Head and Neck Squamous Cell Carcinoma: Systematic Review and Meta-Analysis Ilaria Girolami 1, *, Domenico Damiani 1, Rosa Negro 1, Monir Abousiam 2, Luca Gazzini 2, Luca Calabrese 2 and Esther Hanspeter 1 Citation: Girolami, I.; Damiani, D.; Negro, R.; Abousiam, M.; Gazzini, L.; Calabrese, L.; Hanspeter, E. Prognostic Significance of Tumor–Stroma Ratio (TSR) in Head and Neck Squamous Cell Carcinoma: Systematic Review and Meta-Analysis. Cells 2024, 13, 1772 . [https://doi.org/10.3390/cells13211772](https://doi.org/10.3390/cells13211772) Academic Editor: Joel L. Schwartz Received: 7 October 2024 Revised: 20 October 2024 Accepted: 25 October 2024 Published: 26 October 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Pathology, Provincial Hospital of Bolzano (SABES-ASDAA), Lehrkrankenhaus der Paracelsus Medizinischen Privatuniversität, via Lorenz Böhler, 5, 39100 Bolzano-Bozen, Italy 2 Department of Otolaryngology, Provincial Hospital of Bolzano (SABES-ASDAA), Lehrkrankenhaus der Paracelsus Medizinischen Privatuniversität, 39100 Bolzano-Bozen, Italy * Correspondence: [ilaria.girolami@sabes.it](ilaria.girolami@sabes.it); Tel.: +39-0471-438153 Abstract: The management of head and neck squamous cell carcinoma (HNSCC) relies heavily on TNM staging and WHO histologic grading; however, in recent years, the analysis of prognostic markers expressed in the tumor stroma has gained attention. The tumor–stroma ratio (TSR) quantifies the proportion of tumor tissue relative to the surrounding stromal tissue; it is assessed with the percentage of stromal tissue within the tumor area, with a cutoff point of 50% being widely used to discriminate high-stroma cancer. In this systematic review and meta-analysis, we investigated the potential prognostic role of the TSR in HNSCC. After a literature screening, 24 studies dealing with the TSR and survival outcomes were included. The TSR showed a significant association with overall survival (OS) in both unadjusted and adjusted measures (RR 2.04, CI 1.57–2.65, p < 0.01; HR 2.36 CI 1.89–2.94, p < 0.00001), with an even stronger prognostic potential in oral cavity/oral tongue cancers (RR 2.44 CI 1.84–3.22, p < 0.00001) . The TSR also showed prognostic value when dealing with cancer-specific survival and was associated with a reduction in disease-free survival (DFS) . In particular, the TSR also retained its prognostic role in terms of DFS when specifically considering early-stage cancers in both unadjusted and adjusted analyses (RR 1.81 CI 1.57–2.10, p < 0.00001; HR 2.09 CI 1.58–2.76, p < 0.00001) . Therefore, we conclude that the TSR is a reliable prognostic marker that is easy to assess in routine histological slides and can be effectively implemented in the routine evaluation of HNSCC. Keywords: tumor–stroma ratio; HNSCC; oral cancer; systematic review; meta-analysis; prognostic markers 1. Introduction Head and neck squamous cell carcinoma (HNSCC) constitutes a significant health challenge globally, with about one million new patients each year worldwide, hence being a relevant cause of mortality in some countries [1] . Unfortunately, approximately 60% of HNSCC cases are at an advanced stage (III-IV) at the time of diagnosis, which often correlates with a poor prognosis [2] . Traditionally, the management of these tumors relies heavily on TNM staging and histologic grading. However, these parameters may not always detect aggressive tumors, especially at an early stage (I-II) of HNSCC. Importantly, both TNM stage and WHO grade primarily consider the characteristics relat

FAQs

How does the tumor–stroma ratio (TSR) relate tumor tissue to stromal tissue?

TSR quantifies the proportion of tumor tissue compared with the surrounding stroma by assessing the percentage of stromal tissue within the tumor area. A 50% cutoff is commonly used to distinguish higher-stroma from lower-stroma groups.

What did the review find about TSR and overall survival in HNSCC?

TSR showed a significant association with overall survival in both unadjusted and adjusted analyses, with stronger prognostic potential reported for oral cavity/oral tongue cancers.

How can TSR be evaluated in routine histology practice?

TSR can be assessed on routine hematoxylin and eosin-stained slides by selecting fields that include tumor invasion fronts with the highest stroma content and evaluating areas containing both stroma and tumor while excluding necrosis and major vascular or muscle tissue.

Sep 21, 2026

Upload by Eden