HLA class I and II expression in oropharyngeal squamous cell carcinoma in relation to tumor HPV status and clinical outcome

PLoS One. 2013 Oct 10;8(10):e77025. doi: 10.1371/journal.pone.0077025. eCollection 2013.

Abstract

HPV-DNA positive (HPVDNA+) oropharyngeal squamous cell carcinoma (OSCC) has better clinical outcome than HPV-DNA negative (HPVDNA-) OSCC. Current treatment may be unnecessarily extensive for most HPV+ OSCC, but before de-escalation, additional markers are needed together with HPV status to better predict treatment response. Here the influence of HLA class I/HLA class II expression was explored. Pre-treatment biopsies, from 439/484 OSCC patients diagnosed 2000-2009 and treated curatively, were analyzed for HLA I and II expression, p16(INK4a) and HPV DNA. Absent/weak as compared to high HLA class I intensity correlated to a very favorable disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) in HPVDNA+ OSCC, both in univariate and multivariate analysis, while HLA class II had no impact. Notably, HPVDNA+ OSCC with absent/weak HLA class I responded equally well when treated with induction-chemo-radiotherapy (CRT) or radiotherapy (RT) alone. In patients with HPVDNA- OSCC, high HLA class I/class II expression correlated in general to a better clinical outcome. p16(INK4a) overexpression correlated to a better clinical outcome in HPVDNA+ OSCC. Absence of HLA class I intensity in HPVDNA+ OSCC suggests a very high survival independent of treatment and could possibly be used clinically to select patients for randomized trials de-escalating therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / therapy
  • Carcinoma, Squamous Cell / virology*
  • Cohort Studies
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • DNA, Viral / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HLA Antigens / metabolism*
  • Histocompatibility Antigens Class I / metabolism
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Male
  • Middle Aged
  • Oropharyngeal Neoplasms / diagnosis*
  • Oropharyngeal Neoplasms / metabolism
  • Oropharyngeal Neoplasms / therapy
  • Oropharyngeal Neoplasms / virology*
  • Papillomaviridae / genetics
  • Papillomaviridae / physiology*
  • Prognosis
  • Survival Analysis
  • Treatment Outcome

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • HLA Antigens
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II

Grants and funding

This work was supported by The Swedish Cancer Society; The Swedish Medical Research Council; The Stockholm Cancer Society; Henning and Ida Perssons Foundation; Karolinska Institutet; the Stockholm County Council; the King Gustaf V Jubilee Fund and Laryngfonden. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.