A Novel Digital Score for Abundance of Tumour Infiltrating Lymphocytes Predicts Disease Free Survival in Oral Squamous Cell Carcinoma

Sci Rep. 2019 Sep 16;9(1):13341. doi: 10.1038/s41598-019-49710-z.


Oral squamous cell carcinoma (OSCC) is the most common type of head and neck (H&N) cancers with an increasing worldwide incidence and a worsening prognosis. The abundance of tumour infiltrating lymphocytes (TILs) has been shown to be a key prognostic indicator in a range of cancers with emerging evidence of its role in OSCC progression and treatment response. However, the current methods of TIL analysis are subjective and open to variability in interpretation. An automated method for quantification of TIL abundance has the potential to facilitate better stratification and prognostication of oral cancer patients. We propose a novel method for objective quantification of TIL abundance in OSCC histology images. The proposed TIL abundance (TILAb) score is calculated by first segmenting the whole slide images (WSIs) into underlying tissue types (tumour, lymphocytes, etc.) and then quantifying the co-localization of lymphocytes and tumour areas in a novel fashion. We investigate the prognostic significance of TILAb score on digitized WSIs of Hematoxylin and Eosin (H&E) stained slides of OSCC patients. Our deep learning based tissue segmentation achieves high accuracy of 96.31%, which paves the way for reliable downstream analysis. We show that the TILAb score is a strong prognostic indicator (p = 0.0006) of disease free survival (DFS) on our OSCC test cohort. The automated TILAb score has a significantly higher prognostic value than the manual TIL score (p = 0.0024). In summary, the proposed TILAb score is a digital biomarker which is based on more accurate classification of tumour and lymphocytic regions, is motivated by the biological definition of TILs as tumour infiltrating lymphocytes, with the added advantages of objective and reproducible quantification.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / mortality*
  • Carcinoma, Squamous Cell / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating / cytology
  • Lymphocytes, Tumor-Infiltrating / pathology*
  • Male
  • Middle Aged
  • Mouth Neoplasms / diagnosis
  • Mouth Neoplasms / mortality*
  • Mouth Neoplasms / pathology
  • Squamous Cell Carcinoma of Head and Neck / diagnosis
  • Squamous Cell Carcinoma of Head and Neck / mortality*
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Survival Analysis


  • Biomarkers, Tumor