HLA Class I and II Expression in Oropharyngeal Squamous Cell Carcinoma in Relation to Tumor HPV Status and Clinical Outcome

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, p16INK4a 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. p16INK4a 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.

CD56-positive lymphocyte infiltration in relation to human papillomavirus association and prognostic significance in oropharyngeal squamous cell carcinoma

“…This is supported by recent data showing that loss of high intensity staining of HLA class I, but not HLA class II, correlates to a very favorable prognosis in HPV-DNA positive OSCC, while in HPV-DNA negative OSCC a better clinical outcome correlated with high HLA class I/class II expression. 10,11 While viruses causing persistent infection (e.g., herpesviruses) have evolved mechanisms to evade NK cell responses, 48,49 carcinogenesis is an evolutionary dead end for HPV. This might explain lacking mechanisms to avoid NK cell mediated killing here.…”

“…9 Loss of high intensity staining of HLA class I, but not HLA class II, correlated to a very favorable prognosis in HPV-DNA positive OSCC, while in HPV-DNA negative OSCC a better clinical outcome correlated with high HLA class I/class II expression. 10,11 Natural Killer (NK) cells are part of the innate immune system. They can kill viral infected or tumor cells without normal cell surface HLA expression that have escaped recognition by cytotoxic T cells.…”

HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance

“…37 This conclusion is further supported by the observation in head and neck cancers, where HLA class II antigen expression is related to human papillomavirus infection of the lesions. 40 Altered constitutive and IFNg inducible HLA class II antigen expression in cancer cells…”

Incidence of human papillomavirus positive tonsillar and base of tongue carcinoma: A stabilisation of an epidemic of viral induced carcinoma?

“…Blank controls were treated likewise to exclude cross-contamination between samples. Presence of HPV DNA was analysed by a multiplex bead-based assay for 27 HPV types (HPV 30, 67 and 69 and the 24 types) and beta-globulin on a Mag Pix instrument as described previously [28,29].…”