Characterization of High-Risk HPV/EBV Co-Presence in Pre-Malignant Cervical Lesions and Squamous Cell Carcinomas
High-risk human papillomaviruses (HR-HPVs) are the etiological agents of cervical cancer. However, a low proportion of HR-HPV-infected women finally develop this cancer, which suggests the involvement of additional cofactors. Epstein–Barr virus (EBV) has been detected in cervical squamous cell carci...
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| Format: | Article |
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MDPI AG
2022-04-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/10/5/888 |
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| author | Rancés Blanco Diego Carrillo-Beltrán Juan P. Muñoz Julio C. Osorio Julio C. Tapia Verónica A. Burzio Iván Gallegos Gloria M. Calaf Paola Chabay Francisco Aguayo |
| author_facet | Rancés Blanco Diego Carrillo-Beltrán Juan P. Muñoz Julio C. Osorio Julio C. Tapia Verónica A. Burzio Iván Gallegos Gloria M. Calaf Paola Chabay Francisco Aguayo |
| author_sort | Rancés Blanco |
| collection | DOAJ |
| description | High-risk human papillomaviruses (HR-HPVs) are the etiological agents of cervical cancer. However, a low proportion of HR-HPV-infected women finally develop this cancer, which suggests the involvement of additional cofactors. Epstein–Barr virus (EBV) has been detected in cervical squamous cell carcinomas (SCCs) as well as in low- (LSIL) and high-grade (HSIL) squamous intraepithelial lesions, although its role is unknown. In this study, we characterized HR-HPV/EBV co-presence and viral gene expression in LSIL (<i>n</i> = 22), HSIL (<i>n</i> = 52), and SCC (<i>n</i> = 19) from Chilean women. Additionally, phenotypic changes were evaluated in cervical cancer cells ectopically expressing BamHI-A Rightward Frame 1 (BARF1). BARF1 is a lytic gene also expressed in EBV-positive epithelial tumors during the EBV latency program. HPV was detected in 6/22 (27.3%) LSIL, 38/52 (73.1%) HSIL, and 15/19 (78.9%) SCC cases (<i>p</i> < 0.001). On the other hand, EBV was detected in 16/22 (72.7%) LSIL, 27/52 (51.9%) HSIL, and 13/19 (68.4%) SCC cases (<i>p</i> = 0.177). HR-HPV/EBV co-presence was detected in 3/22 (13.6%) LSIL, 17/52 (32.7%) HSIL, and 11/19 (57.9%) SCC cases (<i>p</i> = 0.020). Additionally, BARF1 transcripts were detected in 37/55 (67.3%) of EBV positive cases and in 19/30 (63.3%) of HR-HPV/EBV positive cases. Increased proliferation, migration, and epithelial-mesenchymal transition (EMT) was observed in cervical cancer cells expressing BARF1. Thus, both EBV and BARF1 transcripts are detected in low- and high-grade cervical lesions as well as in cervical carcinomas. In addition, BARF1 can modulate the tumor behavior in cervical cancer cells, suggesting a role in increasing tumor aggressiveness. |
| first_indexed | 2024-03-10T03:22:53Z |
| format | Article |
| id | doaj.art-31f22cd2424e4bdaaad3f2b99ad34618 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T03:22:53Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-31f22cd2424e4bdaaad3f2b99ad346182023-11-23T12:14:31ZengMDPI AGMicroorganisms2076-26072022-04-0110588810.3390/microorganisms10050888Characterization of High-Risk HPV/EBV Co-Presence in Pre-Malignant Cervical Lesions and Squamous Cell CarcinomasRancés Blanco0Diego Carrillo-Beltrán1Juan P. Muñoz2Julio C. Osorio3Julio C. Tapia4Verónica A. Burzio5Iván Gallegos6Gloria M. Calaf7Paola Chabay8Francisco Aguayo9Laboratorio de Oncovirología, Programa de Virología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380000, ChileLaboratorio de Oncovirología, Programa de Virología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380000, ChileInstituto de Alta Investigación, Universidad de Tarapaca, Arica 1000000, ChilePopulation Registry of Cali, Department of Pathology, Universidad del Valle, Cali 760042, ColombiaLaboratorio de Transformación Celular, Programa Biología Celular y Molecular, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380000, ChileFacultad de Ciencias de la Vida, Universidad Andrés Bello, Fundación Ciencia & Vida, Andes Biotechnologies SpA, Santiago 7780272, ChileServicio de Anatomía Patológica, Hospital Clínico de la Universidad de Chile, Santiago 8380000, ChileInstituto de Alta Investigación, Universidad de Tarapaca, Arica 1000000, ChileLaboratory of Molecular Biology, Pathology Division, Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP-CONICET-GCBA), Ricardo Gutiérrez Children’s Hospital, Buenos Aires C1425EFD, ArgentinaLaboratorio de Oncovirología, Programa de Virología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380000, ChileHigh-risk human papillomaviruses (HR-HPVs) are the etiological agents of cervical cancer. However, a low proportion of HR-HPV-infected women finally develop this cancer, which suggests the involvement of additional cofactors. Epstein–Barr virus (EBV) has been detected in cervical squamous cell carcinomas (SCCs) as well as in low- (LSIL) and high-grade (HSIL) squamous intraepithelial lesions, although its role is unknown. In this study, we characterized HR-HPV/EBV co-presence and viral gene expression in LSIL (<i>n</i> = 22), HSIL (<i>n</i> = 52), and SCC (<i>n</i> = 19) from Chilean women. Additionally, phenotypic changes were evaluated in cervical cancer cells ectopically expressing BamHI-A Rightward Frame 1 (BARF1). BARF1 is a lytic gene also expressed in EBV-positive epithelial tumors during the EBV latency program. HPV was detected in 6/22 (27.3%) LSIL, 38/52 (73.1%) HSIL, and 15/19 (78.9%) SCC cases (<i>p</i> < 0.001). On the other hand, EBV was detected in 16/22 (72.7%) LSIL, 27/52 (51.9%) HSIL, and 13/19 (68.4%) SCC cases (<i>p</i> = 0.177). HR-HPV/EBV co-presence was detected in 3/22 (13.6%) LSIL, 17/52 (32.7%) HSIL, and 11/19 (57.9%) SCC cases (<i>p</i> = 0.020). Additionally, BARF1 transcripts were detected in 37/55 (67.3%) of EBV positive cases and in 19/30 (63.3%) of HR-HPV/EBV positive cases. Increased proliferation, migration, and epithelial-mesenchymal transition (EMT) was observed in cervical cancer cells expressing BARF1. Thus, both EBV and BARF1 transcripts are detected in low- and high-grade cervical lesions as well as in cervical carcinomas. In addition, BARF1 can modulate the tumor behavior in cervical cancer cells, suggesting a role in increasing tumor aggressiveness.https://www.mdpi.com/2076-2607/10/5/888Epstein–Barr virushuman papillomavirusBamHI-A rightward frame 1 expressioncervical cancer |
| spellingShingle | Rancés Blanco Diego Carrillo-Beltrán Juan P. Muñoz Julio C. Osorio Julio C. Tapia Verónica A. Burzio Iván Gallegos Gloria M. Calaf Paola Chabay Francisco Aguayo Characterization of High-Risk HPV/EBV Co-Presence in Pre-Malignant Cervical Lesions and Squamous Cell Carcinomas Microorganisms Epstein–Barr virus human papillomavirus BamHI-A rightward frame 1 expression cervical cancer |
| title | Characterization of High-Risk HPV/EBV Co-Presence in Pre-Malignant Cervical Lesions and Squamous Cell Carcinomas |
| title_full | Characterization of High-Risk HPV/EBV Co-Presence in Pre-Malignant Cervical Lesions and Squamous Cell Carcinomas |
| title_fullStr | Characterization of High-Risk HPV/EBV Co-Presence in Pre-Malignant Cervical Lesions and Squamous Cell Carcinomas |
| title_full_unstemmed | Characterization of High-Risk HPV/EBV Co-Presence in Pre-Malignant Cervical Lesions and Squamous Cell Carcinomas |
| title_short | Characterization of High-Risk HPV/EBV Co-Presence in Pre-Malignant Cervical Lesions and Squamous Cell Carcinomas |
| title_sort | characterization of high risk hpv ebv co presence in pre malignant cervical lesions and squamous cell carcinomas |
| topic | Epstein–Barr virus human papillomavirus BamHI-A rightward frame 1 expression cervical cancer |
| url | https://www.mdpi.com/2076-2607/10/5/888 |
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