Association of the Human Bocavirus With Tonsil Squamous Cell Carcinomas
Background: The human bocavirus (HBoV) is known to persist latently in the infected host cells and seems to replicate its DNA via the DNA damage response system, which is frequently defect in tumors and correlates with microsatellite instability (MSI). Because HBoV is able to persist in the infected...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-10-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2018.02450/full |
| _version_ | 1818041175932665856 |
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| author | Merle Höpken Merle Höpken Isabel Förster Steffen Maune Michael Brockmann Oliver Schildgen Verena Schildgen |
| author_facet | Merle Höpken Merle Höpken Isabel Förster Steffen Maune Michael Brockmann Oliver Schildgen Verena Schildgen |
| author_sort | Merle Höpken |
| collection | DOAJ |
| description | Background: The human bocavirus (HBoV) is known to persist latently in the infected host cells and seems to replicate its DNA via the DNA damage response system, which is frequently defect in tumors and correlates with microsatellite instability (MSI). Because HBoV is able to persist in the infected tissues, induces pro-fibrotic and pro- cancerogenic cytokines in vivo and in vitro, and is detected in colorectal and lung tumors, the virus may be involved in cancerogenesis at least as a cofactor. Recently it was shown that the adenotonsillar tissue is an important site of HBoV1 persistence and replication. Considering the background that approximately 60% of oropharyngeal cancers were thought to be attributable to a HPV infection, a co-participation of HBoV in terms of a chronic virus infection might play a role in the cancerogenesis of tonsil tumors.Methods: Formalin-fixed, paraffin-embedded tonsil tumor samples were screened for HBoV and HPV DNA. Positive tissue sections were afterward subjected to fluorescence in situ hybridization (FISH) analysis to identify HBoV and HPV infected cells. By use of an in vitro cell culture model with primary tonsil fibroblasts, keratinocytes, and lymphocytes infected by HBoV we tried to find the target cells of virus replication. MSI testing was based on a previously published protocol using a de-multiplexed PCR followed by fluorescent detection of PCR products in a capillary sequencing device.Results: In total 62 of 103 (60, 19%) of the tonsil squamous cell carcinomas tested positive for HBoV DNA and 66 of 103 (66%) samples were identified as HPV positive. The FISH analysis revealed both double infection of HPV and HBoV in the same cells as well as single infections of both viruses within the tumor tissue. Twenty-two of 62 HBoV positive tumors tested HPV negative, 40 of 62 tissue sections were HBoV and HPV positive. We analyzed 21 out of the 62 HBoV positive tumors for MSI. Of those four tonsils displayed MSI in at least 1 of 10 microsatellite markers.Conclusion: Our findings support the hypothesis that human bocavirus infections as a cofactor may have an impact on tumor development in tonsils, although it still remains possible that HBoV solely displays a tumor tropism. |
| first_indexed | 2024-12-10T08:26:15Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-10T08:26:15Z |
| publishDate | 2018-10-01 |
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| series | Frontiers in Microbiology |
| spelling | doaj.art-c9db9f5a8cc6476488ffa95aff71372f2022-12-22T01:56:13ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-10-01910.3389/fmicb.2018.02450410715Association of the Human Bocavirus With Tonsil Squamous Cell CarcinomasMerle Höpken0Merle Höpken1Isabel Förster2Steffen Maune3Michael Brockmann4Oliver Schildgen5Verena Schildgen6Klinik für Hals-, Nasen- und Ohrenheilkunde, Kliniken der Stadt Köln, Klinikum der Privaten Universität Witten/Herdecke mit Sitz in Köln, Cologne, GermanyInstitut für Pathologie, Kliniken der Stadt Köln, Klinikum der Privaten Universität Witten/Herdecke mit Sitz in Köln, Cologne, GermanyInstitut für Pathologie, Kliniken der Stadt Köln, Klinikum der Privaten Universität Witten/Herdecke mit Sitz in Köln, Cologne, GermanyKlinik für Hals-, Nasen- und Ohrenheilkunde, Kliniken der Stadt Köln, Klinikum der Privaten Universität Witten/Herdecke mit Sitz in Köln, Cologne, GermanyInstitut für Pathologie, Kliniken der Stadt Köln, Klinikum der Privaten Universität Witten/Herdecke mit Sitz in Köln, Cologne, GermanyInstitut für Pathologie, Kliniken der Stadt Köln, Klinikum der Privaten Universität Witten/Herdecke mit Sitz in Köln, Cologne, GermanyInstitut für Pathologie, Kliniken der Stadt Köln, Klinikum der Privaten Universität Witten/Herdecke mit Sitz in Köln, Cologne, GermanyBackground: The human bocavirus (HBoV) is known to persist latently in the infected host cells and seems to replicate its DNA via the DNA damage response system, which is frequently defect in tumors and correlates with microsatellite instability (MSI). Because HBoV is able to persist in the infected tissues, induces pro-fibrotic and pro- cancerogenic cytokines in vivo and in vitro, and is detected in colorectal and lung tumors, the virus may be involved in cancerogenesis at least as a cofactor. Recently it was shown that the adenotonsillar tissue is an important site of HBoV1 persistence and replication. Considering the background that approximately 60% of oropharyngeal cancers were thought to be attributable to a HPV infection, a co-participation of HBoV in terms of a chronic virus infection might play a role in the cancerogenesis of tonsil tumors.Methods: Formalin-fixed, paraffin-embedded tonsil tumor samples were screened for HBoV and HPV DNA. Positive tissue sections were afterward subjected to fluorescence in situ hybridization (FISH) analysis to identify HBoV and HPV infected cells. By use of an in vitro cell culture model with primary tonsil fibroblasts, keratinocytes, and lymphocytes infected by HBoV we tried to find the target cells of virus replication. MSI testing was based on a previously published protocol using a de-multiplexed PCR followed by fluorescent detection of PCR products in a capillary sequencing device.Results: In total 62 of 103 (60, 19%) of the tonsil squamous cell carcinomas tested positive for HBoV DNA and 66 of 103 (66%) samples were identified as HPV positive. The FISH analysis revealed both double infection of HPV and HBoV in the same cells as well as single infections of both viruses within the tumor tissue. Twenty-two of 62 HBoV positive tumors tested HPV negative, 40 of 62 tissue sections were HBoV and HPV positive. We analyzed 21 out of the 62 HBoV positive tumors for MSI. Of those four tonsils displayed MSI in at least 1 of 10 microsatellite markers.Conclusion: Our findings support the hypothesis that human bocavirus infections as a cofactor may have an impact on tumor development in tonsils, although it still remains possible that HBoV solely displays a tumor tropism.https://www.frontiersin.org/article/10.3389/fmicb.2018.02450/fullhuman bocavirustonsil squamous cell carcinomaoncogenesispersistenceprimary cell culture |
| spellingShingle | Merle Höpken Merle Höpken Isabel Förster Steffen Maune Michael Brockmann Oliver Schildgen Verena Schildgen Association of the Human Bocavirus With Tonsil Squamous Cell Carcinomas Frontiers in Microbiology human bocavirus tonsil squamous cell carcinoma oncogenesis persistence primary cell culture |
| title | Association of the Human Bocavirus With Tonsil Squamous Cell Carcinomas |
| title_full | Association of the Human Bocavirus With Tonsil Squamous Cell Carcinomas |
| title_fullStr | Association of the Human Bocavirus With Tonsil Squamous Cell Carcinomas |
| title_full_unstemmed | Association of the Human Bocavirus With Tonsil Squamous Cell Carcinomas |
| title_short | Association of the Human Bocavirus With Tonsil Squamous Cell Carcinomas |
| title_sort | association of the human bocavirus with tonsil squamous cell carcinomas |
| topic | human bocavirus tonsil squamous cell carcinoma oncogenesis persistence primary cell culture |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2018.02450/full |
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