Comparing serum protein levels can aid in differentiating HPV-negative and -positive oropharyngeal squamous cell carcinoma patients.

Amy Dickinson,Caj Haglund,Stina Syrjänen,Sakari Joenväärä,Reija Randén-Brady,Petri Mattila,Jaana Hagström,Mayank Saraswat,Antti Mäkitie,Suvi Silén,Timo Carpén,Robert Silén,Tiialotta Tohmola,Randall J Kimple

doi:10.1371/journal.pone.0233974

Abstract

BackgroundThe surrogate immunohistochemical marker, p16INK4a, is used in clinical practice to determine the high-risk human papillomavirus (HPV) status of oropharyngeal squamous cell carcinomas (OPSCC). With a specificity of 83%, this will misclassify some patients compared with direct HPV testing. Patients who are p16INK4a-positive but HPV DNA-negative, or RNA-negative, may be unsuitable for treatment de-escalation aimed at reducing treatment-related side effects. We aimed to identify cost-effective serum markers to improve decision making for patients at risk of misclassification by p16INK4a alone.MethodsSerum proteins from pre-treatment samples of 36 patients with OPSCC were identified and quantified using label-free mass spectrometry-based proteomics. HPV-status was determined using p16INK4a/HPV DNA and E6/E7 mRNA. Serum protein expressions were compared between groups of patients according to HPV status, using the unpaired t-test with a Benjamini-Hochberg correction. ROC curves (AUC) were calculated with SPSS (v25).ResultsOf 174 serum proteins identified, complement component C7 (C7), apolipoprotein F (ApoF) and galectin-3-Binding Protein (LGALS3BP) significantly differed between HPV-positive and -negative tumors (AUC ranging from 0.84–0.87). ApoF levels were more than twice as high in the E6/E7 mRNA HPV-positive group than HPV-negative.ConclusionsSerum C7, ApoF and LGALS3BP levels discriminate between HPV-positive and HPV-negative OPSCC. Further studies are needed to validate these host immunity-related proteins as markers for HPV-associated OPSCC.

Highlights

Human papilloma virus (HPV) is an established aetiological factor for oropharyngeal squamous cell carcinoma (OPSCC), with nearly 90% of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCC) being caused by the high-risk genotype HPV16 [1]
Human papilloma virus (HPV) is an established aetiological factor for oropharyngeal squamous cell carcinoma (OPSCC), with nearly 90% of HPV-positive OPSCCs being caused by the high-risk genotype HPV16 [1]
HPV prevalence in OPSCC is globally variable [1,2,3,4,5], and it relates to the methods used for HPV detection as recently shown in a comprehensive assessment suggesting that only 25% of all OPSCCs are HPV positive worldwide [6]

Summary

Introduction

Human papilloma virus (HPV) is an established aetiological factor for oropharyngeal squamous cell carcinoma (OPSCC), with nearly 90% of HPV-positive OPSCCs being caused by the high-risk genotype HPV16 [1]. HPV-positive OPSCCs have a different pattern of histopathological features and clinical behavior compared with HPV-negative OPSCCs [7, 8]. They tend to occur in younger patients, and HPV-positive tumors are more likely to present with nodal metastases, they generally have a favorable prognosis compared with alcohol- and smokingrelated, non-HPV OPSCCs [9,10,11]. The surrogate immunohistochemical marker, p16INK4a, is used in clinical practice to determine the high-risk human papillomavirus (HPV) status of oropharyngeal squamous cell carcinomas (OPSCC). We aimed to identify cost-effective serum markers to improve decision making for patients at risk of misclassification by p16INK4a alone

Objectives

Methods

Conclusion