Clinical evaluation of tumour-infiltrating lymphocytes as a prognostic factor in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma.

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 (TIL _Hi ; diffuse, lymphocytes in >80% of tumour and stroma), moderate (TIL _Mod ; patchy, present in 20-80% of tumour and stroma) or low (TIL _Lo ; 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 TIL _Hi and TIL _Mod patients were compared with TIL _Lo patients (P < 0.0001 for TIL _Hi versus TIL _Lo ; P < 0.0001 for TIL _Mod versus TIL _Lo ). Statistical significance was retained when TIL _Hi and TIL _Mod patients were grouped into a single category (TIL _Hi ) and compared with TIL _Lo 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 TIL _Hi and TIL _Lo on the basis of routine H&E staining stratifies patients into those with potentially favourable and unfavourable survival outcomes, respectively.
(© 2019 John Wiley & Sons Ltd.)