HPV-related oropharyngeal cancer (OPC) patients have favorable prognosis, but around 20% fail to treatment. The HPV16-E5 oncoprotein increases recycling of activated epidermal growth factor receptor (EGFR) to the cell surface, enhancing factor signal transduction. Our aim was to evaluate viral HPV16-E5 oncogene expression as well as EGFR and its activated form, phosphorylated EGFR (pEGFR), protein levels as biomarkers for clinical outcome in a retrospective cohort of OPC patients.
Formalin-fixed-paraffin-embedded OPC were collected from pathology archives. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and p16INK4a immunohistochemistry (IHC). HPV16-positive cases were evaluated for HPV16-E5 (RT-PCR) and EGFR/pEGFR (IHC). A stratified random sample of HPV-negative samples was evaluated for EGFR/pEGFR. Overall survival (OS) and disease-free survival (DFS) estimates were assessed.
Among the 788 OPC patient samples from a retrospective cohort, 54 where double positive for HPV16-DNA and p16INK4a. HPV16-E5 expression was found in 41 samples (77.4%). Expression of EGFR was observed in 37.7% vs 70.8% HPV16-positive and HPV-negative samples, respectively; (adjusted Odds Ratio (OR) 0.15[95%Confident Interval (CI):0.04-0.56]). Expression of pEGFR followed an inverse pattern with 39.6% and 24.9% detection in HPV16-positive and HPV-negative samples, respectively; (adjusted OR 1.58[0.48-5.17]). Within HPV16-positive cases, no association between HPV16-E5 and EGFR or pEGFR was observed. The combination of HPV status and EGFR or pEGFR expression were predictors of OS and DFS.
HPV16-E5 is highly expressed on HPV16-positive OPCs. Interestingly, HPV16-positive cases expressed more pEGFR while HPV-negative cases expressed significantly more EGFR. The combinations of HPV status and EGFR or pEGFR expression are useful biomarkers for prognosis outcome in OPC patients.
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Legal entity responsible for the study
Institut Català d'Oncologia.
This work was supported by a grants from “Ayudas Merck Serono Investigación_Salud 2000” , Instituto de Salud Carlos III-ISCIII (Spanish Government) cofunded by FEDER funds / European Regional Development Fund (ERDF) - a way to build Europe (References: PI1102096, PI1401918, PI1500500, PI1501205, RD12/0036/0056, CIBERESP, CIBERONC), Agència de Gestió d’Ajuts Universitaris i de Recerca (2014SGR756; 2014SGR1077), Beca de recerca clínica 2016 de l'Acadèmia de Ciències Mèdiques de Catalunya i Balears, Beca PERIS-2016-2020 Pla Estratègic de Recerca en Investigacions Sanitàries (SLT002/16/00404), Asociación Española Contra el Cáncer (personal grant to LA), Rio Hortega-SEOM (ISCIII-Spanish Society of Medical Oncology) (personal grant to MT).
All authors have declared no conflicts of interest.