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

TY - JOUR

T1 - Clinical evaluation of tumour-infiltrating lymphocytes as a prognostic factor in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma

AU - Ruangritchankul, Komkrit

AU - Sandison, Ann

AU - Warburton, Fiona

AU - Guerrero-Urbano, Teresa

AU - Reis Ferreira, Miguel

AU - Lei, Mary

AU - Thavaraj, Selvam

N1 - This article is protected by copyright. All rights reserved.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - BACKGROUND: 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 to identify HPV-associated OpSCC patients with poor outcome. 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 sought therefore to determine the clinical prognostic utility of tumour-infiltrating lymphocyte (TIL) evaluation in HPV-associated OpSCC within the context of a diagnostic histopathology setting.METHODS: 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). Inter-observer reliability was assessed, and TILs category was then correlated with overall survival (OS) and disease-free survival (DFS).RESULTS: Univariate and multivariate analysis showed a statistically significant difference in overall and disease-free survival estimates when TILHi and TILMod groups were compared with TILLo patients (p<0.0001 TILHi vs TILLo , p<0.0001 TILMod vs TILLo ). Statistical significance was retained when TILHi and TILMod were grouped into a single category (TILHi ) and compared to TILLo (p<0.0001).CONCLUSION: We demonstrate the prognostic utility of TILs in HPV-associated OpSCC in clinical practice. A binary system classifying HPV-associated OpSCC into TILHi and TILLo on routine H&E staining stratifies patients into potentially favourable and unfavourable survival outcomes, respectively. This article is protected by copyright. All rights reserved.

AB - BACKGROUND: 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 to identify HPV-associated OpSCC patients with poor outcome. 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 sought therefore to determine the clinical prognostic utility of tumour-infiltrating lymphocyte (TIL) evaluation in HPV-associated OpSCC within the context of a diagnostic histopathology setting.METHODS: 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). Inter-observer reliability was assessed, and TILs category was then correlated with overall survival (OS) and disease-free survival (DFS).RESULTS: Univariate and multivariate analysis showed a statistically significant difference in overall and disease-free survival estimates when TILHi and TILMod groups were compared with TILLo patients (p<0.0001 TILHi vs TILLo , p<0.0001 TILMod vs TILLo ). Statistical significance was retained when TILHi and TILMod were grouped into a single category (TILHi ) and compared to TILLo (p<0.0001).CONCLUSION: We demonstrate the prognostic utility of TILs in HPV-associated OpSCC in clinical practice. A binary system classifying HPV-associated OpSCC into TILHi and TILLo on routine H&E staining stratifies patients into potentially favourable and unfavourable survival outcomes, respectively. This article is protected by copyright. All rights reserved.

KW - human papillomavirus

KW - oropharyngeal

KW - tumour-infiltrating lymphocytes

UR - http://www.scopus.com/inward/record.url?scp=85067344011&partnerID=8YFLogxK

U2 - 10.1111/his.13873

DO - 10.1111/his.13873

M3 - Article

C2 - 31144335

SN - 0309-0167

VL - 75

SP - 146

EP - 150

JO - Histopathology

JF - Histopathology

IS - 1

ER -