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Viral Load, Integration and Methylation of E2BS3 and 4 in Human Papilloma Virus (HPV) 16-Positive Vaginal and Vulvar Carcinomas
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.ORCID iD: 0000-0001-9992-266X
Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.ORCID iD: 0000-0003-2317-5738
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Oncology, Örebro University Hospital, Örebro, Sweden.ORCID iD: 0000-0002-5063-631X
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.ORCID iD: 0000-0001-6881-237X
2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 11, article id e112839Article in journal (Refereed) Published
Abstract [en]

Objective: To investigate if viral load, integration and methylation of E2BS3 and 4 represent different ways of tumor transformation in vaginal and vulvar carcinoma and to elucidate its clinical impact.

Methods: Fifty-seven samples, positive for HPV16, were selected for the study. Detection of viral load was made with realtime-PCR using copy numbers of E6 and integration was calculated from comparing E2 to E6-copies. Methylation of E2BS3 and 4 was analysed using bisulphite treatment of tumor DNA, followed by PCR and pyrosequencing.

Results: Vaginal tumors were found to have a higher viral load (p=0.024) compared to vulvar tumors but a high copy number (> median value, 15 000) as well as high methylation (> 50%) was significantly (p=0.010 and p=0.045) associated with a worse cancer-specific survival rate in vulvar carcinoma, but not in vaginal carcinoma. Four groups could be defined for the complete series using a Cluster Two step analysis; (1) tumors holding episomal viral DNA, viral load below 150 000 copies not highly methylated (n=25, 46.3%); (2) tumors harboring episomal viral DNA and being highly methylated (>50%; n=6, 11.1%); (3) tumors with viral DNA fully integrated (n=11, 20.4%), and (4) tumors harboring episomal viral DNA and being medium-or unmethylated (< 50%) and having a high viral load (> total mean value 150 000; n=12, 22.2%). The completely integrated tumors were found to be distinct group, whilst some overlap between the groups with high methylation and high viral load was observed.

Conclusion: HPV16-related integration, methylation in E2BS3 and 4 and viral load may represent different viral characteristics driving vaginal and vulvar carcinogenesis. HPV16-related parameters were found to be of clinical importance in the vulvar series only.

Place, publisher, year, edition, pages
Public Library Science , 2014. Vol. 9, no 11, article id e112839
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:oru:diva-42542DOI: 10.1371/journal.pone.0112839ISI: 000347709300111Scopus ID: 2-s2.0-84911948854OAI: oai:DiVA.org:oru-42542DiVA, id: diva2:787080
Note

Funding Agency:

Örebro County Council Research Committee OLL-324811 OLL-259341

Available from: 2015-02-09 Created: 2015-02-09 Last updated: 2018-06-15Bibliographically approved
In thesis
1. Characterization of HPV-induced vaginal and vulvar carcinoma
Open this publication in new window or tab >>Characterization of HPV-induced vaginal and vulvar carcinoma
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Örebro: Örebro university, 2014. p. 83
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 112
Keywords
vaginal carcinoma, vulvar carcinoma, HPV, integration, methylation, genotyping
National Category
Obstetrics, Gynecology and Reproductive Medicine Cancer and Oncology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-38173 (URN)978-91-7529-052-2 (ISBN)
Public defence
2014-12-19, Universitetssjukhuset, Wilandersalen, Södra Grev Rosengatan, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2014-10-27 Created: 2014-10-27 Last updated: 2017-10-17Bibliographically approved

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Lillsunde-Larsson, GabriellaHelenius, GiselaSorbe, BengtKarlsson, Mats G.

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Lillsunde-Larsson, GabriellaHelenius, GiselaSorbe, BengtKarlsson, Mats G.
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School of Health and Medical Sciences, Örebro University, SwedenÖrebro University HospitalSchool of Medicine, Örebro University, Sweden
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