High mobility group box 1 (HMGB1) is an extremely conserved DNA-binding protein that stabilizes nucleosomes and facilitates gene transcription in mammalian cells. When released extracellularly, HMGB1 becomes an alarmin that can mediate systemic diseases. High mobility group box 1 signals via two main receptors: receptor for advanced glycation end-products (RAGE) and toll-like receptor-4 (TLR4). We hypothesized that HMGB1 expression is increased in patients with oral lichen planus (OLP) relative to healthy controls. Therefore, HMGB1 and its receptors were mapped in tissue biopsies from 25 patients with OLP and from 20 healthy controls by immunostaining and ImageJ analysis. High mobility group box 1 was induced in oral keratinocytes in all patients with OLP. The band-like cell infiltrate in patients with OLP revealed very strong staining for RAGE. Likewise, TLR4 was overexpressed throughout OLP mucosa which co-localized with HMGB1. In conclusion, we suggest that OLP could partly be an HMGB1-mediated condition by creating a proinflammatory loop cycle via RAGE- and TLR4-signalling axes, which may contribute to the chronicity of this disease.

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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