Exploring the combination of tumor‐stroma ratio, tumor‐infiltrating lymphocytes, and tumor budding with WHO histopathological grading on early‐stage oral squamous cell carcinoma prognosis

• Published in: Journal of oral pathology & medicine 2023-05, Vol.52 (5), p.402-409
• Main Authors: Silva, Gabriela Vivili Domingues, Silva Dolens, Eder, Paranaíba, Lívia Máris Ribeiro, Ayroza, Ana Lúcia Carrinho, Gurgel Rocha, Clarissa Araujo, Almangush, Alhadi, Salo, Tuula, Brennan, Peter A., Coletta, Ricardo D.
• Format: Article
• Language: English
• Subjects: Cancer; Carcinoma, Squamous Cell - pathology; Head and Neck Neoplasms - pathology; histopathological features; Humans; Lymphocytes; Lymphocytes, Tumor-Infiltrating; Medical prognosis; Mouth Neoplasms - pathology; Multivariate analysis; Neoplasm Grading; Neoplasm Staging; Oral cancer; Oral carcinoma; Oral squamous cell carcinoma; Prognosis; Regression analysis; Retrospective Studies; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - pathology; Stroma; tumor budding; Tumors; tumor‐stroma ratio; WHO grading system; World Health Organization
• ISSN: 0904-2512; 1600-0714
• DOI: 10.1111/jop.13359

Background While the relevance of the World Health Organization histopathological grading system as a prognostic tool for oral squamous cell carcinoma has received many critics, other histopathological features such as tumor‐stroma ratio, tumor‐infiltrating lymphocytes, and tumor budding are displaying promising results. Here, we evaluated the prognostic impact of the incorporation of tumor‐stroma ratio, tumor‐infiltrating lymphocytes, and tumor budding into World Health Organization histopathological grading for patients with oral squamous cell carcinoma. Methods A total of 95 patients with early‐stage oral squamous cell carcinoma were enrolled in the study, and World Health Organization tumor grading, tumor‐stroma ratio, tumor‐infiltrating lymphocytes, and tumor budding were evaluated in surgical slides stained with hematoxylin and eosin. Survival analyses for cancer‐specific survival and disease‐free survival were performed using Cox regression models, and receiver operating characteristic curves were applied for assessment of the performance of the combinations. Results Tumor‐stroma ratio (stroma‐rich) was significantly and independently associated with both shortened cancer‐specific survival and poor disease‐free survival, individually and in combination with World Health Organization histopathological grading. The combination of tumor‐stroma ratio with World Health Organization grading did not improve the discriminatory ability compared to tumor‐stroma ratio alone. Although low tumor‐infiltrating lymphocytes were associated with shortened cancer‐specific survival, the association did not withstand multivariate analysis. However, in combination with World Health Organization grading, low tumor‐infiltrating lymphocytes were independently associated with poor cancer‐specific survival. The combination of tumor‐infiltrating lymphocytes and World Health Organization histopathological grading displayed a better discrimination of poor cancer‐specific survival than tumor‐infiltrating lymphocytes alone, but not at a significant level. Conclusion Our findings support tumor‐stroma ratio as a potential prognostic marker for patients with oral squamous cell carcinoma, and the incorporation of tumor‐infiltrating lymphocytes into the World Health Organization grading system improves the prognostic ability of the tumor grading alone.