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Peer-reviewedCC BY-NC-ND 4.0BMC Cancer

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

  • Derya Aksu1
  • Gülsüm Şeyma Yalçın2
  • Necmettin Karasu3
  • Selçuk Kuzu4
  • Çiğdem Özdemir1
  • Uğur Aksu1,5
5 affiliations
  1. 1Department of Medical Pathology, Faculty of Medicine, Afyonkarahisar Health Sciences University, Afyonkarahisar, Türkiye
  2. 2Department of Medical Pathology, Afyon State Hospital, Afyonkarahisar, Türkiye
  3. 3Department of Plastic, Reconstructive and Aesthetic Surgery, Park Hayat Hospital, Afyonkarahisar, Türkiye
  4. 4Department of Otorhinolaryngology, Afyonkarahisar Health Sciences University, Afyonkarahisar, Türkiye
  5. 5Department of Cardiology, Faculty of Medicine, Afyonkarahisar Health Sciences University, Afyonkarahisar, Türkiye
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{aksu2026tumor,
  title = {{Tumor budding and tumor-associated lymphocytic response as histopathological indicators of high-risk disease in head and neck cutaneous squamous cell carcinoma}},
  author = {Derya Aksu and Gülsüm Şeyma Yalçın and Necmettin Karasu and Selçuk Kuzu and Çiğdem Özdemir and Uğur Aksu},
  journal = {BMC Cancer},
  year = {2026},
  month = aug,
  doi = {10.1186/s12885-026-16653-4},
  url = {https://doi.org/10.1186/s12885-026-16653-4},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Tumor budding and tumor-associated lymphocytic response as histopathological indicators of high-risk disease in head and neck cutaneous squamous cell carcinoma
AU  - Derya Aksu
AU  - Gülsüm Şeyma Yalçın
AU  - Necmettin Karasu
AU  - Selçuk Kuzu
AU  - Çiğdem Özdemir
AU  - Uğur Aksu
PY  - 2026
DA  - 2026/08/04
JO  - BMC Cancer
DO  - 10.1186/s12885-026-16653-4
UR  - https://doi.org/10.1186/s12885-026-16653-4
AB  - 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.
SN  - 1471-2407
ER  -