Characterization of High-Risk HPV/EBV Co-Presence in Pre-Malignant Cervical Lesions and Squamous Cell Carcinomas

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

doi:10.3390/microorganisms10050888

Characterization of High-Risk HPV/EBV Co-Presence in Pre-Malignant Cervical Lesions and Squamous Cell Carcinomas

Título traducido de la contribución: Caracterización de la coexistencia de VPH/VEB de alto riesgo en lesiones cervicales premalignas y carcinomas de células escamosas

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

Instituto de Alta Investigación

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

10 Citas (Scopus)

Resumen

Los virus del papiloma humano de alto riesgo (VPH-AR) son los agentes etiológicos del cáncer de cuello uterino. Sin embargo, una baja proporción de mujeres infectadas con VPH-AR finalmente desarrollan este cáncer, lo que sugiere la participación de cofactores adicionales. El virus de Epstein-Barr (VEB) se ha detectado en carcinomas de células escamosas (CCE) de cuello uterino, así como en lesiones intraepiteliales escamosas de grado bajo (LSIL) y alto (HSIL), aunque se desconoce su papel. En este estudio, caracterizamos la copresencia de VPH-AR/VEB y la expresión génica viral en LSIL (n = 22), HSIL (n = 52) y CCE (n = 19) de mujeres chilenas. Además, se evaluaron los cambios fenotípicos en células de cáncer de cuello uterino que expresan ectópicamente BamHI-A Rightward Frame 1 (BARF1). BARF1 es un gen lítico que también se expresa en tumores epiteliales positivos para VEB durante el programa de latencia del VEB. Se detectó VPH en 6/22 (27,3%) casos de LSIL, 38/52 (73,1%) de HSIL y 15/19 (78,9%) de CCE (p < 0,001). Por otro lado, se detectó VEB en 16/22 (72,7%) casos de LSIL, 27/52 (51,9%) de HSIL y 13/19 (68,4%) de CCE (p = 0,177). Se detectó la coexistencia de VPH-AR y VEB en 3/22 (13,6%) casos de LSIL, 17/52 (32,7%) de HSIL y 11/19 (57,9%) de CCE (p = 0,020). Además, se detectaron transcritos de BARF1 en 37/55 (67,3%) de los casos positivos para VEB y en 19/30 (63,3%) de los casos positivos para VPH-AR/VEB. Se observó un aumento de la proliferación, la migración y la transición epitelio-mesenquimal (TEM) en las células de cáncer de cuello uterino que expresan BARF1. Por lo tanto, tanto los transcritos de VEB como los de BARF1 se detectan en lesiones cervicales de bajo y alto grado, así como en carcinomas cervicales. Además, BARF1 puede modular el comportamiento tumoral en las células de cáncer de cuello uterino, lo que sugiere un papel en el aumento de la agresividad tumoral.

Título traducido de la contribución	Caracterización de la coexistencia de VPH/VEB de alto riesgo en lesiones cervicales premalignas y carcinomas de células escamosas
Idioma original	Inglés
Número de artículo	888
Publicación	Microorganisms
Volumen	10
N.º	5
DOI	https://doi.org/10.3390/microorganisms10050888
Estado	Publicada - 23 abr. 2022

Palabras clave

Expresión del marco derecho 1 de BamHI-A
Cáncer de cuello uterino
Virus de Epstein-Barr
Virus del papiloma humano

ODS de las Naciones Unidas

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@article{2252ae89764340a9baf9275077a62370,

title = "Characterization of High-Risk HPV/EBV Co-Presence in Pre-Malignant Cervical Lesions and Squamous Cell Carcinomas",

abstract = "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 in-traepithelial lesions, although its role is unknown. In this study, we characterized HR-HPV/EBV co-presence and viral gene expression in LSIL (n = 22), HSIL (n = 52), and SCC (n = 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 (p < 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 (p = 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 (p = 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.",

keywords = "BamHI-A rightward frame 1 expression, Cervical cancer, Epstein–Barr virus, Human papillomavirus, Expresi{\'o}n del marco derecho 1 de BamHI-A, C{\'a}ncer de cuello uterino, Virus de Epstein-Barr, Virus del papiloma humano",

author = "Ranc{\'e}s Blanco and Diego Carrillo-Beltr{\'a}n and Mu{\~n}oz, \{Juan P.\} and Osorio, \{Julio C.\} and Tapia, \{Julio C.\} and Burzio, \{Ver{\'o}nica A.\} and Iv{\'a}n Gallegos and Calaf, \{Gloria M.\} and Paola Chabay and Francisco Aguayo",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = apr,

day = "23",

doi = "10.3390/microorganisms10050888",

language = "English",

volume = "10",

journal = "Microorganisms",

issn = "2076-2607",

number = "5",

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TY - JOUR

T1 - Characterization of High-Risk HPV/EBV Co-Presence in Pre-Malignant Cervical Lesions and Squamous Cell Carcinomas

AU - Blanco, Rancés

AU - Carrillo-Beltrán, Diego

AU - Muñoz, Juan P.

AU - Osorio, Julio C.

AU - Tapia, Julio C.

AU - Burzio, Verónica A.

AU - Gallegos, Iván

AU - Calaf, Gloria M.

AU - Chabay, Paola

AU - Aguayo, Francisco

PY - 2022/4/23

Y1 - 2022/4/23

N2 - 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 in-traepithelial lesions, although its role is unknown. In this study, we characterized HR-HPV/EBV co-presence and viral gene expression in LSIL (n = 22), HSIL (n = 52), and SCC (n = 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 (p < 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 (p = 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 (p = 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.

AB - 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 in-traepithelial lesions, although its role is unknown. In this study, we characterized HR-HPV/EBV co-presence and viral gene expression in LSIL (n = 22), HSIL (n = 52), and SCC (n = 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 (p < 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 (p = 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 (p = 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.

KW - BamHI-A rightward frame 1 expression

KW - Cervical cancer

KW - Epstein–Barr virus

KW - Human papillomavirus

KW - Expresión del marco derecho 1 de BamHI-A

KW - Cáncer de cuello uterino

KW - Virus de Epstein-Barr

KW - Virus del papiloma humano

UR - https://www.scopus.com/pages/publications/85128833013

U2 - 10.3390/microorganisms10050888

DO - 10.3390/microorganisms10050888

M3 - Article

AN - SCOPUS:85128833013

SN - 2076-2607

VL - 10

JO - Microorganisms

JF - Microorganisms

IS - 5

M1 - 888

ER -

Characterization of High-Risk HPV/EBV Co-Presence in Pre-Malignant Cervical Lesions and Squamous Cell Carcinomas

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ODS de las Naciones Unidas

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