The Use of HPV16-E5, EGFR, and pEGFR as Prognostic Biomarkers for Oropharyngeal Cancer Patients
Por:
Taberna, M, Torres, M, Alejo, M, Mena, M, Tous, S, Marquez, S, Pavon, MA, Leon, X, Garcia, J, Guix, M, Hijano, R, Bonfill, T, Aguila, A, Lozano, A, Mesia, R, Alemany, L, Bravo, IG
Publicada:
11 dic 2018
Resumen:
Background: Anti-epidermal-growth-factor-receptor (EGFR) therapies in combination with radiotherapy are being studied on de-escalation clinical trials for HPV-related oropharyngeal cancer (OPC) patients. The HPV16-E5 oncoprotein increases recycling of activated EGFR to the cell surface, enhancing factor signal transduction. Our aim was to evaluate viral HPV16-E5 oncogene expression as well as EGFR and phosphorylated-EGFR (pEGFR), protein levels as biomarkers for clinical outcome in a retrospective cohort of OPC patients.
Methods: Formalin-fixed-paraffin-embedded OPCs were collected from 1990 to 2013. OPC samples containing HPV-DNA were subject to viral E6* I mRNA detection and p16(INK4a) immunohistochemistry (IHC). HPV16-positive cases were evaluated for HPV16-E5 (RT-PCR) and EGFR/pEGFR (IHC). A stratified and matched random sample of HPV-negative samples was used as control and evaluated for EGFR/pEGFR. Overall survival (OS) and disease free survival (DFS) estimates were assessed for locally advanced OPC patients (stage III, IVa, b 7th edition).
Results: Among 788 OPC patient samples, 53 were double positive for HPV16-DNA/p(16INK4a). HPV16-E5 expression was found in 41 of 53 samples (77.4%). EGFR expression was observed in 37.7 vs 70.8% of HPV16-positive vs HPV-negative samples, respectively; (adjusted OR = 0.15) 5% 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; (adjusted OR = 1.58 [95% CI = 0.48-5.17]). Within HPV16-positive cases, no association between HPV16-E5/EGFR nor pEGFR was observed. With a median follow-up of 39.36 months (min = 0.03 - max = 272.07), the combination of HPV status and EGFR or pEGFR expression were predictors of better OS (p < 0.001, for both) and DFS (p < 0.001 for EGFR and p = 0.003 for pEGFR).
Conclusions: HPV16-E5 is highly expressed on HPV16-positive OPCs. Interestingly, HPV16-positive cases expressed significantly more pEGFR while HPV-negative cases expressed more EGFR. The combinations of HPV status and EGFR or pEGFR may be useful biomarkers for evaluating prognosis outcome in OPC patients.
Filiaciones:
Taberna, M:
Catalan Inst Oncol ICO, Dept Med Oncol, IDIBELL, ONCOBELL, Barcelona, Spain
Catalan Inst Oncol ICO, Canc Epidemiol Res Program, IDIBELL, Barcelona, Spain
Univ Barcelona, Dept Med, Barcelona, Spain
Torres, M:
Catalan Inst Oncol ID BELL, Canc Epidemiol Res Program, Infect & Canc Lab, Barcelona, Spain
Alejo, M:
Hosp Gen LHospitalet, Dept Pathol, Barcelona, Spain
Mena, M:
Catalan Inst Oncol ICO, Canc Epidemiol Res Program, IDIBELL, Barcelona, Spain
Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
Tous, S:
Catalan Inst Oncol ICO, Canc Epidemiol Res Program, IDIBELL, Barcelona, Spain
Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
Marquez, S:
Catalan Inst Oncol ICO, Canc Epidemiol Res Program, IDIBELL, Barcelona, Spain
Pavon, MA:
Catalan Inst Oncol ID BELL, Canc Epidemiol Res Program, Infect & Canc Lab, Barcelona, Spain
Leon, X:
Hosp Santa Creu & Sant Pau, Otorhinolaryngol Dept, Barcelona, Spain
CIBER BBN, Madrid, Spain
Garcia, J:
Catalan Inst Oncol ICO, Dept Med Oncol, IDIBELL, ONCOBELL, Barcelona, Spain
Guix, M:
Hosp del Mar, IMIM, Canc Res Program, Barcelona, Spain
Hosp del Mar, Dept Med Oncol, Barcelona, Spain
Hijano, R:
Hosp del Mar, Dept Otorhinolaryngol, Barcelona, Spain
Bonfill, T:
Hosp Univ Parc Tauli, Dept Med Oncol, Barcelona, Spain
Aguila, A:
Hosp Univ Parc Tauli, Dept Otorhinoleryngol, Barcelona, Spain
Lozano, A:
Catalan Inst Oncol ICO, Dept Radiat Oncol, Barcelona, Spain
Mesia, R:
Catalan Inst Oncol ICO, Dept Med Oncol, IDIBELL, ONCOBELL, Barcelona, Spain
Univ Barcelona, Dept Med, Barcelona, Spain
Catalan Inst Oncol ICO, Dept Med Oncol, Barcelona, Spain
Alemany, L:
Catalan Inst Oncol ICO, Canc Epidemiol Res Program, IDIBELL, Barcelona, Spain
Inst Salud Carlos III, CIBERESP, Madrid, Spain
Bravo, IG:
CNRS IRD Uni Montp, French Natl Ctr Sci Res, CNRS, Lab MIVEGEC, Montpellier, France
Gold, Green Published
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