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Background <p>Tumor budding (TB) and tumor-associated lymphocytic response (TALR) have emerged as promising histopathological indicators of tumor aggressiveness across epithelial malignancies. Recent studies have suggested that both tumor invasive activity and host immune response contribute substantially to disease progression in cutaneous squamous cell carcinoma (cSCC). However, data evaluating their combined significance in head and neck cSCC remain limited.</p> Methods <p>A retrospective cohort of 187 primary head and neck cSCC cases was analyzed. TB was graded using a three-tier system, and TALR was categorized into three inflammatory response patterns. Associations with clinicopathological characteristics were evaluated using univariate analyses. Multivariable logistic regression was performed to identify factors independently associated with high-risk disease, defined as advanced pathological stage (T3–T4).</p> Results <p>High-grade TB was significantly associated with adverse histopathological characteristics, including poor differentiation, increased depth of invasion, aggressive invasion pattern, perineural invasion, lymphovascular invasion, and advanced pathological stage (all <i>p</i> &lt; 0.001). Weak TALR was associated with infiltrative growth characteristics and older age. In multivariable analysis, Grade 3&#xa0;TB (OR 6.75, 95% CI 2.33–19.57), tumor depth &gt; 6&#xa0;mm (OR 4.03, 95% CI 2.03–8.38), poor differentiation (OR 2.64, 95% CI 1.06–6.61), aggressive invasion pattern (OR 3.07, 95% CI 1.43–6.60), and weak TALR (OR 2.29, 95% CI 1.12–4.69) remained independently associated with high-risk disease.</p> Conclusions <p>Tumor budding and tumor-associated lymphocytic response were independently associated with histopathological features of high-risk disease in head and neck cSCC. Their combined assessment may provide additional information for pathological risk stratification and may support incorporation into routine histopathological evaluation. Prospective studies incorporating recurrence and survival outcomes are required before definitive prognostic conclusions can be established.</p>

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Tumor budding and tumor-associated lymphocytic response as histopathological indicators of high-risk disease in head and neck cutaneous squamous cell carcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月4日

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  • Derya Aksu,
  • Gülsüm Şeyma Yalçın,
  • Necmettin Karasu,
  • Selçuk Kuzu,
  • Çiğdem Özdemir,
  • Uğur Aksu,
  • Derya Aksu

摘要

Background

Tumor budding (TB) and tumor-associated lymphocytic response (TALR) have emerged as promising histopathological indicators of tumor aggressiveness across epithelial malignancies. Recent studies have suggested that both tumor invasive activity and host immune response contribute substantially to disease progression in cutaneous squamous cell carcinoma (cSCC). However, data evaluating their combined significance in head and neck cSCC remain limited.

Methods

A retrospective cohort of 187 primary head and neck cSCC cases was analyzed. TB was graded using a three-tier system, and TALR was categorized into three inflammatory response patterns. Associations with clinicopathological characteristics were evaluated using univariate analyses. Multivariable logistic regression was performed to identify factors independently associated with high-risk disease, defined as advanced pathological stage (T3–T4).

Results

High-grade TB was significantly associated with adverse histopathological characteristics, including poor differentiation, increased depth of invasion, aggressive invasion pattern, perineural invasion, lymphovascular invasion, and advanced pathological stage (all p < 0.001). Weak TALR was associated with infiltrative growth characteristics and older age. In multivariable analysis, Grade 3 TB (OR 6.75, 95% CI 2.33–19.57), tumor depth > 6 mm (OR 4.03, 95% CI 2.03–8.38), poor differentiation (OR 2.64, 95% CI 1.06–6.61), aggressive invasion pattern (OR 3.07, 95% CI 1.43–6.60), and weak TALR (OR 2.29, 95% CI 1.12–4.69) remained independently associated with high-risk disease.

Conclusions

Tumor budding and tumor-associated lymphocytic response were independently associated with histopathological features of high-risk disease in head and neck cSCC. Their combined assessment may provide additional information for pathological risk stratification and may support incorporation into routine histopathological evaluation. Prospective studies incorporating recurrence and survival outcomes are required before definitive prognostic conclusions can be established.