Clinical evaluation of tumour‐infiltrating lymphocytes as a prognostic factor in patients with human papillomavirus‐associated oropharyngeal squamous cell carcinoma. Issue 1 (10th June 2019) - Ruangritchankul, Komkrit
Abstract : Clinical evaluation of tumour‐infiltrating lymphocytes as a prognostic factor in patients with human papillomavirus‐associated oropharyngeal squamous cell carcinoma Aims: The majority of patients with human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma (OpSCC) have favourable survival outcomes, but a significant minority of individuals will die of their disease. There are currently no definitive criteria with which to identify HPV‐associated OpSCC patients with poor outcomes. Recent reports suggest that quantitative evaluation of T‐cell subpopulations in OpSCC may be of prognostic value, but the methods used have limited utility in a clinical diagnostic setting. We therefore sought to determine the clinical prognostic utility of tumour‐infiltrating lymphocyte (TIL) evaluation in patients with HPV‐associated OpSCC within the context of a diagnostic histopathology setting. Methods and results: Representative diagnostic haematoxylin and eosin (H&E)‐stained slides from 232 consecutive HPV‐associated OpSCC patients were classified as containing a high (TILHi ; diffuse, lymphocytes in >80% of tumour and stroma), moderate (TILMod ; patchy, present in 20–80% of tumour and stroma) or low (TILLo ; sparse or absent, present in <20% of tumour and stroma) TILs. Interobserver reliability was assessed, and TIL category was then correlated with overall survival (OS) and disease‐free survival (DFS). Univariate and multivariate analyses showed statistically significant differences in OS and DFS estimates when TILHi and TILMod patients were compared with TILLo patients ( P < 0.0001 for TILHi versus TILLo ; P < 0.0001 for TILMod versus TILLo ). Statistical significance was retained when TILHi and TILMod patients were grouped into a single category (TILHi ) and compared with TILLo patients ( P < 0.0001). Conclusion: We demonstrate the prognostic utility of TILs in patients with HPV‐associated OpSCC in clinical practice. A binary system classifying HPV‐associated OpSCC into TILHi and TILLo on the basis of routine H&E staining stratifies patients into those with potentially favourable and unfavourable survival outcomes, respectively.