Dataset Information

The Use of HPV16-E5, EGFR, and pEGFR as Prognostic Biomarkers for Oropharyngeal Cancer Patients.

ABSTRACT: 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 p16INK4a 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/p16INK4a. 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.

SUBMITTER: Taberna M

PROVIDER: S-EPMC6297752 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The Use of HPV16-E5, EGFR, and pEGFR as Prognostic Biomarkers for Oropharyngeal Cancer Patients.

Taberna Miren M Torres Montserrat M Alejo María M Mena Marisa M Tous Sara S Marquez Sandra S Pavón Miquel A MA León Xavier X García Jacinto J Guix Marta M Hijano Rafael R Bonfill Teresa T Aguilà Antón A Lozano Alicia A Mesía Ricard R Alemany Laia L Bravo Ignacio G IG

Frontiers in oncology 20181211

<b>Background:</b> 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-<i>E5</i> oncogene expression as well as EGFR and phosphorylated-EGFR (pEGFR), protein levels as biomarkers for clinical outcome in ...[more]

PMID: 30619735

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Project description:Severe xerostomia is noted in the majority of patients irradiated for oropharyngeal cancer (OPC). Extracellular microRNAs (miRNAs) may serve as effective tools allowing prediction of radiation-related toxicity. The aim of this study was to create an efficient prognostic miRNA-based test for severe, patient-rated xerostomia 3 months after primary treatment. This prospective study enrolled OPC patients treated between 2016 and 2018 in three centers in Poland. The primary endpoint was severe (grade ≥3) xerostomia as assessed by the EORTC H&N-35 questionnaires. Initially, a group of 10 patients with severe xerostomia was randomly selected and matched with a comparative group of 10 patients without severe xerostomia. Samples were collected before RT, after receiving 20 Gy and within 24 hours after treatment completion. qPCR arrays (QIAGEN, Hilden, Germany) were used to quantify expression levels of 752 miRNAs in the serum at all timepoints. The resulting logistic-regression based model was validated in additional 60 patients: 30 with grade >3 xerostomia and 30 without. Of 152 eligible patients, we successfully recruited 111 patients. Severe xerostomia 3 months after treatment was reported by 63 patients (56.8%). Mean dose delivered to parotid glands was higher in both exploratory and validation cohort. The model based on miR-185-5p and miR-425-5p expression levels measured before the start of radiotherapy had AUC 0.96 (95% CI: 0.88-1.00). The model based on the same miRNAs remained robust when parameters were measured after 20 Gy (AUC 0.90 (95% CI: 0.75-1.00)). These results were confirmed in the validation group. In the validation group pre-radiotherapy model application yielded 73.3% sensitivity and 80.0% specificity. In the samples taken after 20 Gy, the same two miRNAs yielded 67.7% sensitivity and 72.4% specificity. The model including pretreatment miR-185-5p and miR-425-5p levels together with mean parotid dose, yielded 90.0% sensitivity and 80.0% specificity. In the validation cohort, this model yielded 80.6 % sensitivity and 55.2 % specificity. The model based on miRNA levels measured after 20 Gy and mean parotid dose had 80.0 % sensitivity and 100% specificity in the exploratory group. In the validation cohort its performance fell to 71.0 % sensitivity and 58.6 % specificity. Serum expression levels of miR-425-5p and miR-185-5p measured before the start of radiotherapy or during therapy (after 20 Gy) had a significant prognostic value for the occurrence of severe xerostomia 3 months after treatment completion. The variability explained by miRNAs appears to be, at least partially, independent from the one related to the dosimetric data.

Dataset Information

The Use of HPV16-E5, EGFR, and pEGFR as Prognostic Biomarkers for Oropharyngeal Cancer Patients.

Publications

The Use of HPV16-E5, EGFR, and pEGFR as Prognostic Biomarkers for Oropharyngeal Cancer Patients.

Similar Datasets

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