Epstein–Barr Virus, But Not Human Papillomavirus, Is Associated With Preinvasive and Invasive Ocular Surface Squamous Neoplasias in Zambian Patients
BackgroundThe etiopathogenesis of ocular surface squamous neoplasia (OSSN) is not fully understood. We assessed the frequency of oncogenic viruses in OSSN by immunohistochemistry (IHC) and polymerase chain reaction (PCR) for human papillomavirus (HPV), Epstein–Barr virus (EBV), Merkel cell polyomavi...
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.864066/full |
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| author | Peter Julius Stepfanie N. Siyumbwa Phyllis Moonga Fred Maate Trevor Kaile Gleb Haynatski Veenu Minhas Jazmine Snow Kerstin Peterson Patience Gihozo Sam Streeter Salan Kaur Annika Evans Daniela Gonzalez Kandali Samwel Guobin Kang John T. West Charles Wood Peter C. Angeletti |
| author_facet | Peter Julius Stepfanie N. Siyumbwa Phyllis Moonga Fred Maate Trevor Kaile Gleb Haynatski Veenu Minhas Jazmine Snow Kerstin Peterson Patience Gihozo Sam Streeter Salan Kaur Annika Evans Daniela Gonzalez Kandali Samwel Guobin Kang John T. West Charles Wood Peter C. Angeletti |
| author_sort | Peter Julius |
| collection | DOAJ |
| description | BackgroundThe etiopathogenesis of ocular surface squamous neoplasia (OSSN) is not fully understood. We assessed the frequency of oncogenic viruses in OSSN by immunohistochemistry (IHC) and polymerase chain reaction (PCR) for human papillomavirus (HPV), Epstein–Barr virus (EBV), Merkel cell polyomavirus (MCPyV), Kaposi sarcoma virus, and adenovirus. Cases from Zambia were prospectively enrolled using a cross-sectional study design between November 2017 and March 2020.MethodsDemographic and clinical data [age, sex, HIV status, antiretroviral therapy (ART) history, CD4 count, plasma viral load] and tumor biopsies were collected from 243 consenting patients. Tumor samples were bisected, and half was used for DNA isolation, while the other half was formalin fixed and paraffin embedded (FFPE) for histopathology analysis. The expressions of latent EBV nuclear antigen 1 (EBNA1), CDKN2A/p16INK4A (p16), and MCPyV large T-antigen (LT) were tested by IHC. Multiplex PCR was used to detect 16 HPV genotypes and four other DNA tumor viruses [Kaposi’s sarcoma-associated herpesvirus (KSHV), EBV, MCPyV, and adenovirus]. Relationships between HIV status, viral DNA and protein expression, and tumor grades were determined by statistical analysis.ResultsOSSN tumors from patients were 29.6% preinvasive and 70.4% invasive. Patients presented with unilateral tumors that were 70.4% late stage (T3/T4). OSSN patients were HIV positive (72.8%). IHC on 243 FFPE biopsies resulted in the detection of EBNA1 (EBV), p16 high-risk HPV (HR-HPV), and MCPyV LT expression in 89.0%, 4.9%, and 0.0%, respectively. EBNA1 was expressed in all grades of preinvasive [cornea–conjunctiva intraepithelial neoplasia (CIN)1, 100%; CIN2, 85.7%; CIN3, 95.8%; and carcinoma in situ (CIS), 83.8%] and in invasive (89.2%) OSSN. PCR on 178 samples detected EBV, HR-HPV, and MCPyV in 80.3%, 9.0%, and 13.5% of tumors, respectively. EBV was detected in all grades of preinvasive and invasive OSSN. EBV detection was associated with high HIV viral loads (p = 0.022). HR-HPV was detected in 0.0% CIN1, 0.0% CIN2, 5.6% CIN3, 13.0% CIS, and 7.0% invasive OSSN.ConclusionsOur findings of EBV DNA and EBNA1 protein in all the grades of preinvasive and especially invasive OSSN are consistent with a potential causal role for EBV in OSSN. A role of HPV in OSSN was not clearly established in this study. |
| first_indexed | 2024-04-14T01:16:47Z |
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| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-14T01:16:47Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-65506195b8694a58b517077a37570b462022-12-22T02:20:49ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-04-011210.3389/fonc.2022.864066864066Epstein–Barr Virus, But Not Human Papillomavirus, Is Associated With Preinvasive and Invasive Ocular Surface Squamous Neoplasias in Zambian PatientsPeter Julius0Stepfanie N. Siyumbwa1Phyllis Moonga2Fred Maate3Trevor Kaile4Gleb Haynatski5Veenu Minhas6Jazmine Snow7Kerstin Peterson8Patience Gihozo9Sam Streeter10Salan Kaur11Annika Evans12Daniela Gonzalez13Kandali Samwel14Guobin Kang15John T. West16Charles Wood17Peter C. Angeletti18Department of Pathology and Microbiology, School of Medicine, Lusaka, ZambiaDepartment of Pathology and Microbiology, School of Medicine, Lusaka, ZambiaUniversity Teaching Hospital, Eye Hospital, Lusaka, ZambiaDepartment of Pathology and Microbiology, School of Medicine, Lusaka, ZambiaDepartment of Pathology and Microbiology, School of Medicine, Lusaka, ZambiaDepartment of Biostatistics, University of Nebraska Medical Center, Omaha, NE, United StatesDepartment of Biostatistics, University of Nebraska Medical Center, Omaha, NE, United StatesNebraska Center for Virology and the School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, United StatesNebraska Center for Virology and the School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, United StatesNebraska Center for Virology and the School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, United StatesNebraska Center for Virology and the School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, United StatesNebraska Center for Virology and the School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, United StatesNebraska Center for Virology and the School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, United StatesNebraska Center for Virology and the School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, United StatesOcean Road Cancer Institute, Dar es Salaam, TanzaniaDepartment of Interdisciplinary Oncology, Louisiana State University Health Science Center, New Orleans, LA, United StatesDepartment of Interdisciplinary Oncology, Louisiana State University Health Science Center, New Orleans, LA, United StatesDepartment of Interdisciplinary Oncology, Louisiana State University Health Science Center, New Orleans, LA, United StatesNebraska Center for Virology and the School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, United StatesBackgroundThe etiopathogenesis of ocular surface squamous neoplasia (OSSN) is not fully understood. We assessed the frequency of oncogenic viruses in OSSN by immunohistochemistry (IHC) and polymerase chain reaction (PCR) for human papillomavirus (HPV), Epstein–Barr virus (EBV), Merkel cell polyomavirus (MCPyV), Kaposi sarcoma virus, and adenovirus. Cases from Zambia were prospectively enrolled using a cross-sectional study design between November 2017 and March 2020.MethodsDemographic and clinical data [age, sex, HIV status, antiretroviral therapy (ART) history, CD4 count, plasma viral load] and tumor biopsies were collected from 243 consenting patients. Tumor samples were bisected, and half was used for DNA isolation, while the other half was formalin fixed and paraffin embedded (FFPE) for histopathology analysis. The expressions of latent EBV nuclear antigen 1 (EBNA1), CDKN2A/p16INK4A (p16), and MCPyV large T-antigen (LT) were tested by IHC. Multiplex PCR was used to detect 16 HPV genotypes and four other DNA tumor viruses [Kaposi’s sarcoma-associated herpesvirus (KSHV), EBV, MCPyV, and adenovirus]. Relationships between HIV status, viral DNA and protein expression, and tumor grades were determined by statistical analysis.ResultsOSSN tumors from patients were 29.6% preinvasive and 70.4% invasive. Patients presented with unilateral tumors that were 70.4% late stage (T3/T4). OSSN patients were HIV positive (72.8%). IHC on 243 FFPE biopsies resulted in the detection of EBNA1 (EBV), p16 high-risk HPV (HR-HPV), and MCPyV LT expression in 89.0%, 4.9%, and 0.0%, respectively. EBNA1 was expressed in all grades of preinvasive [cornea–conjunctiva intraepithelial neoplasia (CIN)1, 100%; CIN2, 85.7%; CIN3, 95.8%; and carcinoma in situ (CIS), 83.8%] and in invasive (89.2%) OSSN. PCR on 178 samples detected EBV, HR-HPV, and MCPyV in 80.3%, 9.0%, and 13.5% of tumors, respectively. EBV was detected in all grades of preinvasive and invasive OSSN. EBV detection was associated with high HIV viral loads (p = 0.022). HR-HPV was detected in 0.0% CIN1, 0.0% CIN2, 5.6% CIN3, 13.0% CIS, and 7.0% invasive OSSN.ConclusionsOur findings of EBV DNA and EBNA1 protein in all the grades of preinvasive and especially invasive OSSN are consistent with a potential causal role for EBV in OSSN. A role of HPV in OSSN was not clearly established in this study.https://www.frontiersin.org/articles/10.3389/fonc.2022.864066/fullocular surface squamous neoplasiahuman papillomavirusEpstein–Barr virushuman immunodeficiency virusZambia |
| spellingShingle | Peter Julius Stepfanie N. Siyumbwa Phyllis Moonga Fred Maate Trevor Kaile Gleb Haynatski Veenu Minhas Jazmine Snow Kerstin Peterson Patience Gihozo Sam Streeter Salan Kaur Annika Evans Daniela Gonzalez Kandali Samwel Guobin Kang John T. West Charles Wood Peter C. Angeletti Epstein–Barr Virus, But Not Human Papillomavirus, Is Associated With Preinvasive and Invasive Ocular Surface Squamous Neoplasias in Zambian Patients Frontiers in Oncology ocular surface squamous neoplasia human papillomavirus Epstein–Barr virus human immunodeficiency virus Zambia |
| title | Epstein–Barr Virus, But Not Human Papillomavirus, Is Associated With Preinvasive and Invasive Ocular Surface Squamous Neoplasias in Zambian Patients |
| title_full | Epstein–Barr Virus, But Not Human Papillomavirus, Is Associated With Preinvasive and Invasive Ocular Surface Squamous Neoplasias in Zambian Patients |
| title_fullStr | Epstein–Barr Virus, But Not Human Papillomavirus, Is Associated With Preinvasive and Invasive Ocular Surface Squamous Neoplasias in Zambian Patients |
| title_full_unstemmed | Epstein–Barr Virus, But Not Human Papillomavirus, Is Associated With Preinvasive and Invasive Ocular Surface Squamous Neoplasias in Zambian Patients |
| title_short | Epstein–Barr Virus, But Not Human Papillomavirus, Is Associated With Preinvasive and Invasive Ocular Surface Squamous Neoplasias in Zambian Patients |
| title_sort | epstein barr virus but not human papillomavirus is associated with preinvasive and invasive ocular surface squamous neoplasias in zambian patients |
| topic | ocular surface squamous neoplasia human papillomavirus Epstein–Barr virus human immunodeficiency virus Zambia |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.864066/full |
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