Koivikko Tiina, Rodrigues Priscila Campioni, Vehviläinen Mari, Hyvönen Petra, Sundquist Elias, Arffman Riikka K, Al-Samadi Ahmed, Välimaa Hanna, Salo Tuula, Risteli Maija
Research Unit of Population Health, Faculty of Medicine, University of Oulu, Oulu, Finland.
Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland.
Front Pharmacol. 2023 May 10;14:1182152. doi: 10.3389/fphar.2023.1182152. eCollection 2023.
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. 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. 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. 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.
口腔舌鳞状细胞癌(OTSCC)是口腔中最常见的癌症。关于单纯疱疹病毒1型(HSV-1)与口腔鳞状细胞癌的关系,已观察到相互矛盾的结果。在此,我们旨在研究HSV-1或HSV-2在口腔HSV感染中的优势,并调查OTSCC中HSV-1的存在及其对癌细胞活力和侵袭的影响。从赫尔辛基大学医院实验室数据库中确定了取自疑似口腔HSV感染的诊断样本中HSV-1和HSV-2的分布情况。然后,我们使用免疫组织化学染色分析了67份OTSCC样本中的HSV-1感染情况。我们进一步使用六种浓度(0.00001 - 1.0感染复数[MOI])测试了HSV-1对高侵袭性转移性HSC-3和低侵袭性原发性SCC-25 OTSCC细胞系活力的影响,以及两种浓度(0.001和0.1 MOI)对其侵袭的影响,采用MTT和Myogel包被的Transwell侵袭试验。在研究期间,共321份口咽样本被诊断为HSV阳性。与HSV-2(在2.2%的样本中检测到)相比,HSV-1是主要的HSV类型(97.8%)。在24%的OTSCC样本中也检测到了HSV-1,且其与患者生存或复发无关。即使在HSV-1病毒载量较低(0.00001、0.0001、0.001 MOI)的情况下,OTSCC细胞在6天后仍具有活力。在两种细胞系中,0.001 MOI均未影响细胞侵袭。然而,0.1 MOI显著降低了HSC-3细胞的侵袭能力。在口腔中,与HSV-2相比,HSV-1感染更为常见。在OTSCC样本中检测到HSV-1,但无临床意义,低剂量的HSV-1不影响OTSCC细胞的存活或侵袭。