University of Oulu

Koivikko T, Rodrigues PC, Vehviläinen M, Hyvönen P, Sundquist E, Arffman RK, Al-Samadi A, Välimaa H, Salo T and Risteli M (2023) Detection of herpes simplex virus in oral tongue squamous cell carcinoma. Front. Pharmacol. 14:1182152. doi: 10.3389/fphar.2023.1182152

Detection of herpes simplex virus in oral tongue squamous cell carcinoma

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Author: Koivikko, Tiina1,2; Rodrigues, Priscila Campioni1,2; Vehviläinen, Mari3;
Organizations: 1Research Unit of Population Health, Faculty of Medicine, University of Oulu, Oulu, Finland
2Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
3Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland
4Department of Health and Social Management, University of Eastern Finland, Kuopio, Finland
5Finnish Student Health Service, Helsinki, Finland
6Research Unit of Biomedicine, Faculty of Medicine, University of Oulu, Oulu, Finland
7Department of Virology, University of Helsinki, Helsinki, Finland
8HUSLAB, Department of Virology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
9HUSLAB, Department of Pathology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.2 MB)
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Language: English
Published: Frontiers Media, 2023
Publish Date: 2023-07-04


Introduction: Oral tongue squamous cell carcinoma (OTSCC) is the most common cancer of the oral cavity. Contradictory results have been observed on the involvement of herpes simplex virus 1 (HSV-1) in oral squamous cell carcinomas. Here, we aimed to study the predominance of HSV-1 or HSV-2 in oral HSV infections and to investigate the presence of HSV-1 in OTSCC and its effect on carcinoma cell viability and invasion.

Methods: The distribution of HSV types one and two in diagnostic samples taken from suspected oral HSV infections was determined from the Helsinki University Hospital Laboratory database. We then analysed 67 OTSCC samples for HSV-1 infection using immunohistochemical staining. We further tested the effects of HSV-1 using six concentrations (0.00001–1.0 multiplicity of infection [MOI]) on viability and two concentrations (0.001 and 0.1 MOI) on invasion of highly invasive metastatic HSC-3 and less invasive primary SCC-25 OTSCC cell lines using MTT and Myogel-coated Transwell invasion assays.

Results: Altogether 321 oropharyngeal samples were diagnosed positive for HSV during the study period. HSV-1 was the predominant (97.8%) HSV type compared with HSV-2 (detected in 2.2% of samples). HSV-1 was also detected in 24% of the OTSCC samples and had no association with patient survival or recurrence. OTSCC cells were viable even after 6 days with low viral load (0.00001, 0.0001, 0.001 MOI) of HSV-1. In both cell lines, 0.001 MOI did not affect cell invasion. However, 0.1 MOI significantly reduced cell invasion in HSC-3 cells.

Discussion: HSV-1 infection is predominant compared with HSV-2 in the oral cavity. HSV-1 is detected in OTSCC samples without clinical significance, and OTSCC cell survival or invasion was not affected at low doses of HSV-1.

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Series: Frontiers in pharmacology
ISSN: 1663-9812
ISSN-E: 1663-9812
ISSN-L: 1663-9812
Volume: 14
Article number: 1182152
DOI: 10.3389/fphar.2023.1182152
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: The work was supported by research grants from the Sigrid Juselius Foundation, Cancer Foundation of Finland, Medical Research Center Oulu, and research funds from the Medical Faculty of the University of Oulu and Helsinki and Oulu University Hospital, and Helsinki University Central Hospital special state support for research.
Copyright information: © 2023 Koivikko, Rodrigues, Vehviläinen, Hyvönen, Sundquist, Arffman, Al-Samadi, Välimaa, Salo and Risteli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.