Peritumoral cuffing by T-cell tumor-infiltrating lymphocytes distinguishes HPV-related oropharyngeal squamous cell carcinoma from oral cavity squamous cell carcinoma

J Oral Pathol Med. 2017 Nov;46(10):972-978. doi: 10.1111/jop.12605. Epub 2017 Jul 14.

Abstract

Background: It is unclear why human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) has improved clinical behavior compared to HPV-negative HNSCC. We sought to better characterize the immune microenvironment of tongue cancers by examining the CD3 and CD8 TIL pattern in HPV-positive and HPV-negative tumors.

Methods: Histologic sections from 40 oral tongue and oropharyngeal cases were analyzed (n=21 HPV DNA-positive, n=19 HPV DNA-negative). CD3 and CD8 T-cell immunostaining were performed on whole-slide sections to quantify tumor-infiltrating lymphocyte (TIL) density and assess its morphology.

Results: A subset of cases (HPV-positive) displayed a unique TIL pattern consisting of circumferential peritumoral population T cells, which was absent in the HPV-negative cases. The presence of peritumoral cuffing was strongly predictive of improved recurrence-free survival compared to cases that lacked this morphologic pattern of immune infiltrate. Four HPV-positive cases lacked the pattern, including two cases with disease recurrence.

Conclusions: For the first time, we show an architectural pattern of immune infiltrate in HNSCC is seen exclusively in HPV-positive patients with improved recurrence-free survival and suggests an organized host immunological response contributes to disease control.

Keywords: tongue SCC; tumor-infiltrating lymphocytes.

MeSH terms

  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / virology*
  • Diagnosis, Differential
  • Female
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / pathology*
  • Head and Neck Neoplasms / virology*
  • Humans
  • Lymphocytes, Tumor-Infiltrating*
  • Male
  • Middle Aged
  • Oropharyngeal Neoplasms / immunology
  • Oropharyngeal Neoplasms / pathology*
  • Oropharyngeal Neoplasms / virology*
  • Papillomaviridae*
  • Papillomavirus Infections / complications*
  • Retrospective Studies
  • Squamous Cell Carcinoma of Head and Neck
  • T-Lymphocytes*
  • Tongue Neoplasms / immunology
  • Tongue Neoplasms / pathology*
  • Tongue Neoplasms / virology*