Serum HPV16 E7 Oncoprotein Is a Recurrence Marker of Oropharyngeal Squamous Cell Carcinomas
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 studie...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/13/3370 |
| _version_ | 1797528101853331456 |
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| author | Lucia Oton-Gonzalez John Charles Rotondo Carmen Lanzillotti Elisa Mazzoni Ilaria Bononi Maria Rosa Iaquinta Luca Cerritelli Nicola Malagutti Andrea Ciorba Chiara Bianchini Stefano Pelucchi Mauro Tognon Fernanda Martini |
| author_facet | Lucia Oton-Gonzalez John Charles Rotondo Carmen Lanzillotti Elisa Mazzoni Ilaria Bononi Maria Rosa Iaquinta Luca Cerritelli Nicola Malagutti Andrea Ciorba Chiara Bianchini Stefano Pelucchi Mauro Tognon Fernanda Martini |
| author_sort | Lucia Oton-Gonzalez |
| collection | DOAJ |
| description | 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 (<i>n</i> = 67) and controls (<i>n</i> = 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 (<i>p</i> < 0.001). Classical markers correlated with improved OS (<i>p</i> < 0.05). Serological studies showed similar proportions of HPV16 L1 antibodies in all HNSCCs (<i>p</i> > 0.05). Serum E7 oncoprotein was present in 30% HPV-positive patients at diagnosis (<i>p</i> > 0.05) and correlated to HNSCC HPV16 E7 mRNA (<i>p</i> < 0.01), whereas it was associated to worse RFS and OS, especially for oropharyngeal squamous cell carcinoma (OPSCC) (<i>p</i> < 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. |
| first_indexed | 2024-03-10T09:53:20Z |
| format | Article |
| id | doaj.art-f198ee5805cf4776a3df32f212fd226e |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T09:53:20Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f198ee5805cf4776a3df32f212fd226e2023-11-22T02:36:48ZengMDPI AGCancers2072-66942021-07-011313337010.3390/cancers13133370Serum HPV16 E7 Oncoprotein Is a Recurrence Marker of Oropharyngeal Squamous Cell CarcinomasLucia Oton-Gonzalez0John Charles Rotondo1Carmen Lanzillotti2Elisa Mazzoni3Ilaria Bononi4Maria Rosa Iaquinta5Luca Cerritelli6Nicola Malagutti7Andrea Ciorba8Chiara Bianchini9Stefano Pelucchi10Mauro Tognon11Fernanda Martini12Department of Medical Sciences, University of Ferrara, 44121 Ferrara, ItalyDepartment of Medical Sciences, University of Ferrara, 44121 Ferrara, ItalyDepartment of Medical Sciences, University of Ferrara, 44121 Ferrara, ItalyDepartment of Medical Sciences, University of Ferrara, 44121 Ferrara, ItalyDepartment of Translational Medicine and for Romagna, University of Ferrara, 44121 Ferrara, ItalyDepartment of Medical Sciences, University of Ferrara, 44121 Ferrara, ItalyENT Unit, Department of Neuroscience and Rehabilitation, University Hospital of Ferrara, 44121 Ferrara, ItalyENT Unit, Department of Neuroscience and Rehabilitation, University Hospital of Ferrara, 44121 Ferrara, ItalyENT Unit, Department of Neuroscience and Rehabilitation, University Hospital of Ferrara, 44121 Ferrara, ItalyENT Unit, Department of Neuroscience and Rehabilitation, University Hospital of Ferrara, 44121 Ferrara, ItalyENT Unit, Department of Neuroscience and Rehabilitation, University Hospital of Ferrara, 44121 Ferrara, ItalyDepartment of Medical Sciences, University of Ferrara, 44121 Ferrara, ItalyDepartment of Medical Sciences, University of Ferrara, 44121 Ferrara, ItalyDespite 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 (<i>n</i> = 67) and controls (<i>n</i> = 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 (<i>p</i> < 0.001). Classical markers correlated with improved OS (<i>p</i> < 0.05). Serological studies showed similar proportions of HPV16 L1 antibodies in all HNSCCs (<i>p</i> > 0.05). Serum E7 oncoprotein was present in 30% HPV-positive patients at diagnosis (<i>p</i> > 0.05) and correlated to HNSCC HPV16 E7 mRNA (<i>p</i> < 0.01), whereas it was associated to worse RFS and OS, especially for oropharyngeal squamous cell carcinoma (OPSCC) (<i>p</i> < 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.https://www.mdpi.com/2072-6694/13/13/3370human papillomavirusoropharyngeal squamous cell carcinomatreatment de-escalationpatient stratificationE7 oncoproteinHPV DNA |
| spellingShingle | Lucia Oton-Gonzalez John Charles Rotondo Carmen Lanzillotti Elisa Mazzoni Ilaria Bononi Maria Rosa Iaquinta Luca Cerritelli Nicola Malagutti Andrea Ciorba Chiara Bianchini Stefano Pelucchi Mauro Tognon Fernanda Martini Serum HPV16 E7 Oncoprotein Is a Recurrence Marker of Oropharyngeal Squamous Cell Carcinomas Cancers human papillomavirus oropharyngeal squamous cell carcinoma treatment de-escalation patient stratification E7 oncoprotein HPV DNA |
| title | Serum HPV16 E7 Oncoprotein Is a Recurrence Marker of Oropharyngeal Squamous Cell Carcinomas |
| title_full | Serum HPV16 E7 Oncoprotein Is a Recurrence Marker of Oropharyngeal Squamous Cell Carcinomas |
| title_fullStr | Serum HPV16 E7 Oncoprotein Is a Recurrence Marker of Oropharyngeal Squamous Cell Carcinomas |
| title_full_unstemmed | Serum HPV16 E7 Oncoprotein Is a Recurrence Marker of Oropharyngeal Squamous Cell Carcinomas |
| title_short | Serum HPV16 E7 Oncoprotein Is a Recurrence Marker of Oropharyngeal Squamous Cell Carcinomas |
| title_sort | serum hpv16 e7 oncoprotein is a recurrence marker of oropharyngeal squamous cell carcinomas |
| topic | human papillomavirus oropharyngeal squamous cell carcinoma treatment de-escalation patient stratification E7 oncoprotein HPV DNA |
| url | https://www.mdpi.com/2072-6694/13/13/3370 |
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