Despite improved prognosis for many HPV-positive head and neck squamous cell carcinomas (HNSCCs), some cases are still marked by recurrence and metastasis. Our study aimed to identify novel biomarkers for patient stratification. Classical HPV markers: HPV-DNA, p16 and HPV mRNA expression were studied in HNSCC (n = 67) and controls (n = 58) by qPCR. Subsequently, ELISA tests were used for HPV16 L1 antibody and HPV16 E7 oncoprotein detection in serum at diagnosis and follow-up. All markers were correlated to relapse-free survival (RFS) and overall survival (OS). HPV-DNA was found in HNSCCs (29.85%), HPV16-DNA in 95% of cases, HPV16 E7 mRNA was revealed in 93.75%. p16 was overexpressed in 75% of HPV-positive HNSCC compared to negative samples and controls (p < 0.001). Classical markers correlated with improved OS (p < 0.05). Serological studies showed similar proportions of HPV16 L1 antibodies in all HNSCCs (p > 0.05). Serum E7 oncoprotein was present in 30% HPV-positive patients at diagnosis (p > 0.05) and correlated to HNSCC HPV16 E7 mRNA (p < 0.01), whereas it was associated to worse RFS and OS, especially for oropharyngeal squamous cell carcinoma (OPSCC) (p < 0.01). Detection of circulating HPV16 E7 oncoprotein at diagnosis may be useful for stratifying and monitoring HPV-positive HNSCC patients for worse prognosis, providing clinicians a tool for selecting patients for treatment de-escalation.

Serum HPV16 E7 oncoprotein is a recurrence marker of Oropharyngeal Squamous Cell Carcinomas

Oton-Gonzalez, Lucia
Primo
Writing – Original Draft Preparation
;
Rotondo, John Charles
Secondo
Investigation
;
Lanzillotti, Carmen
Writing – Review & Editing
;
Mazzoni, Elisa
Software
;
Bononi, Ilaria
Data Curation
;
Iaquinta, Maria Rosa
Investigation
;
Cerritelli, Luca
Resources
;
Malagutti, Nicola
Resources
;
Ciorba, Andrea
Resources
;
Bianchini, Chiara
Resources
;
Pelucchi, Stefano
Supervision
;
Tognon, Mauro
Penultimo
Funding Acquisition
;
Martini, Fernanda
Ultimo
Project Administration
2021

Abstract

Despite improved prognosis for many HPV-positive head and neck squamous cell carcinomas (HNSCCs), some cases are still marked by recurrence and metastasis. Our study aimed to identify novel biomarkers for patient stratification. Classical HPV markers: HPV-DNA, p16 and HPV mRNA expression were studied in HNSCC (n = 67) and controls (n = 58) by qPCR. Subsequently, ELISA tests were used for HPV16 L1 antibody and HPV16 E7 oncoprotein detection in serum at diagnosis and follow-up. All markers were correlated to relapse-free survival (RFS) and overall survival (OS). HPV-DNA was found in HNSCCs (29.85%), HPV16-DNA in 95% of cases, HPV16 E7 mRNA was revealed in 93.75%. p16 was overexpressed in 75% of HPV-positive HNSCC compared to negative samples and controls (p < 0.001). Classical markers correlated with improved OS (p < 0.05). Serological studies showed similar proportions of HPV16 L1 antibodies in all HNSCCs (p > 0.05). Serum E7 oncoprotein was present in 30% HPV-positive patients at diagnosis (p > 0.05) and correlated to HNSCC HPV16 E7 mRNA (p < 0.01), whereas it was associated to worse RFS and OS, especially for oropharyngeal squamous cell carcinoma (OPSCC) (p < 0.01). Detection of circulating HPV16 E7 oncoprotein at diagnosis may be useful for stratifying and monitoring HPV-positive HNSCC patients for worse prognosis, providing clinicians a tool for selecting patients for treatment de-escalation.
Oton-Gonzalez, Lucia; Rotondo, John Charles; Lanzillotti, Carmen; Mazzoni, Elisa; Bononi, Ilaria; Iaquinta, Maria Rosa; Cerritelli, Luca; Malagutti, Nicola; Ciorba, Andrea; Bianchini, Chiara; Pelucchi, Stefano; Tognon, Mauro; Martini, Fernanda
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11392/2460572
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