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

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

Anders Näsman  1 , Emilia Andersson, Linda Marklund, Nikolaos Tertipis, Lalle Hammarstedt-Nordenvall, Per Attner, Tommy Nyberg, Giuseppe V Masucci, Eva Munck-Wikland, Torbjörn Ramqvist, Tina Dalianis
Affiliations

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

Anders Näsman et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: Co-author Torbjörn Ramqvist is a PLOS ONE editor. This has not altered the authors' adherence to all the PLOS ONE policies on sharing data and materials as detailed online in the guideline for authors.

Figures

Figure 1
Figure 1. Kaplan-Meier curves for disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) in patients with HPV positive oropharyngeal squamous cell carcinoma (OSCC) with known HLA class I expression.
(A) DFS stratified for HCA-2 intensity, (B) DSS stratified for HCA-2 intensity, (C) OS stratified for HCA-2 intensity, (D) DFS stratified for HC-10 intensity, (E) DSS stratified for HC-10 intensity, and (F) OS stratified for HC-10 intensity. HPVDNA+ OSCC with absent HLA class I intensity had a significant better clinical outcome than tumors with strong HLA class I intensity, while weak intensity staining presented an intermediate survival (HCA-2: DFS p<0.001; DSS p=0.060; OS p=0.022; HC-10: DFS p=0.003, DSS p=0.021 and OS p=0.009, with the log-rank test). Notably, the difference observed in the HCA-2 DSS analysis did not reach significance, although the trend was similar.
Figure 2
Figure 2. Survival presented with Kaplan-Meier curves, and analyzed using the logrank test, for disease-specific survival (DSS) in patients with HPV-positive oropharyngeal squamous cell carcinoma (HPVDNA+ OSCC) with known HLA class I intensity and different treatment regimes.
(A) DSS in HPVDNA+ OSCC with absent HCA-2 intensity stratified for radiotherapy (RT) and induction chemotherapy-RT, (B) DSS in HPVDNA+ OSCC with weak HCA-2 intensity stratified for radiotherapy (RT) and induction chemotherapy-RT, (C) DSS in HPVDNA+ OSCC with strong HCA-2 intensity stratified for radiotherapy (RT) and induction chemotherapy-RT, (D) DSS in HPVDNA+ OSCC with absent HC-10 intensity stratified for radiotherapy (RT) and induction chemotherapy-RT, (E) DSS in HPVDNA+ OSCC with weak HC-10 intensity stratified for radiotherapy (RT) and induction chemotherapy-RT, (F) DSS in HPVDNA+ OSCC with strong HC-10 intensity stratified for radiotherapy (RT) and induction chemotherapy-RT.
Figure 3
Figure 3. Survival presented with Kaplan-Meier curves, and analyzed using the logrank test, for disease-free survival (DFS), in patients with HPV-positive (HPVDNA+) and p16INK4a positive/negative oropharyngeal squamous cell carcinoma (OSCC).
(A) DFS in HPVDNA+ p16INK4a positive OSCC stratified for HCA-2 intensity (p=0.016), (B) DFS in HPVDNA+ p16INK4a negative OSCC stratified for HCA-2 intensity (p=0.072), (C) DFS in HPVDNA+ p16INK4a positive OSCC stratified for HC-10 intensity (p=0.024), (D) DFS in HPVDNA+ p16INK4a negative OSCC stratified for HC-10 intensity (p=0.083).
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