Impact of human papillomavirus on the tumor microenvironment in oropharyngeal squamous cell carcinoma

Int J Cancer. 2022 Feb 1;150(3):521-531. doi: 10.1002/ijc.33849. Epub 2021 Nov 3.

Abstract

Increasing evidence has elucidated the clinicopathological significance of tumor microenvironment (TME) cells. However, TME differences associated with human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC) have not been well characterized. In our study, we comprehensively determined the TME infiltration patterns in 315 OPSCC patients, and systematically correlated the TME phenotypes with genomic characteristics and clinical features of OPSCCs. In this way, we observed the enrichment of high endothelial cells and adaptive immune cells in HPV-positive (HPV+) OPSCCs, in contrast to the enrichment of fibroblasts and capillary endothelial cells in HPV- negative (HPV-) OPSCCs. By focusing on immune checkpoint genes, we constructed a coexpression network using genes that were differentially expressed between HPV+ and HPV- OPSCCs. Functional analysis of the network indicated that HPV+ OPSCCs had elevated immune activities by promoting adaptive immune response and suppressing activities related to extracellular matrix organization. Subsequently, clinical analysis showed that identified TME-relevant genes were closely associated with the prognosis and therapy response in OPSCC. Importantly, results from the TME analysis were further validated using an independent OPSCC cohort.

Keywords: RNA-seq; human papillomavirus; oropharyngeal cancer; tumor microenvironment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Communication
  • Female
  • Humans
  • Immune Checkpoint Proteins / genetics
  • Male
  • Middle Aged
  • Oropharyngeal Neoplasms / mortality
  • Oropharyngeal Neoplasms / pathology
  • Oropharyngeal Neoplasms / virology*
  • Papillomaviridae / isolation & purification*
  • Prognosis
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Squamous Cell Carcinoma of Head and Neck / virology*
  • Tumor Microenvironment / physiology*

Substances

  • Immune Checkpoint Proteins