Immunohistochemical biomarkers and volumetric parameters for predicting radiotherapy-based outcomes in patients with p16-negative pharyngeal cancer.

Ji-An Liang,Kuo-Yang Yen,Shu-Fen Chiang,Shang-Wen Chen,Shih-Neng Yang,Tze-Yi Lin,Rui-Yun Chen,Te-Chun Hsieh,Ying-Chun Lin,Yao-Ching Wang,Ya-Huey Chen,Chia-Hung Kao

doi:10.18632/oncotarget.20374

Abstract

BackgroundThis study determined the prognostic effects of immunohistochemical biomarkers and volumetric parameters predicting radiotherapy-based treatment in patients with p16-negative squamous cell carcinoma of the oropharynx or hypopharynx.ResultsVEGF immunoreactivity > 2 and GLUT1 overexpression were prognostic factors for lower cause-specific survival. Moreover, both factors were associated with lower disease-free survival. The predictors of lower primary relapse-free survival were VEGF immunoreactivity > 2 and CT-based gross tumor volume > 16 mL.Materials and MethodsImmunohistochemical biomarkers in pretreatment biopsy specimens from 60 patients with p16-negative cancer were analyzed using tissue microarrays. Computed tomography (CT)-based and biological tumor volumes were retrieved through fluorodeoxyglucose positron emission tomography-CT. Correlations of cause-specific, disease-free, and primary relapse-free survival with volumetric parameters and the immunohistochemical biomarker score were investigated.ConclusionsFor patients with p16-negative pharyngeal cancer receiving radiotherapy, treatment outcomes can be stratified by VEGF and GLUT1 expression and CT-based gross tumor volume.

Highlights

Human papilloma virus (HPV) infection has become increasingly apparent as a major risk factor for head and neck cancer [1, 2]
For patients with p16-negative pharyngeal cancer receiving radiotherapy, treatment outcomes can be stratified by VEGF and GLUT1 expression and Computed tomography (CT)-based gross tumor volume
By combining the biological tumor volume determined using fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET-CT) and some immunohistochemical markers, our previous study showed an overexpression of certain endogenous markers associated with increased FDG uptake and treatment outcomes [21]

Summary

Introduction

Human papilloma virus (HPV) infection has become increasingly apparent as a major risk factor for head and neck cancer [1, 2]. HPV-positive tumors are clinically, pathologically, and etiologically distinct and are more responsive to treatment [3, 4]. Despite their occurrence in the same tissue, evidence suggests a biological distinction between HPV-positive and HPVnegative head and neck cancers [5]. Several studies have assessed the ability of various endogenous hypoxic, radioresistant, and proliferative biomarkers to predict treatment outcomes [9,10,11,12,13,14,15,16,17,18,19,20], few studies have analyzed HPVnegative cancer cohorts. This study determined the prognostic effects of immunohistochemical biomarkers and volumetric parameters predicting radiotherapy-based treatment in patients with p16-negative squamous cell carcinoma of the oropharynx or hypopharynx

Methods

Results

Conclusion