Background: The surveillance methods oral squamous cell carcinoma (OSCC) patients may be chosen by considering the risk for recurrence, and it is important to establish appropriate methods during the period in which latent/dormant cancer cells become more apparent. To investigate the appropriate surveillance of patients with OSCC based on the individual risk for recurrence and/or metastasis, we performed a retrospective cohort study after the complete surgical resection of OSCC as the primary treatment. Methods: The study was performed in 324 patients with OSCC who had been primarily treated with surgery from 2007 to 2020 at our hospital. We investigated the period, timing, and methods (visual examination, palpation and imaging using FDG-PET/CT or CECT) for surveillance in each case that comprised postsurgical treatment. Results: Regarding the time to occurrence of postsurgical events, we found that half of cases of local recurrence, cervical lymph node metastasis, and distant metastasis occurred within 200 days, and 75% of all of these events occurred within 400 days. However, the mean time for second primary cancer was 1589 days. The postsurgical events were detected earlier by imaging examinations than they were by visual examination and palpation. Conclusions: For the surveillance of patients with OSCC after primary surgery, it is desirable to perform FDG-PET/CT within 3–6 months and at 1 year after surgery and to consider CECT as an option in between FDG-PET/CT, while continuing history and physical examinations for about 5 years based on individual risk assessment.

TSC-22 (TGF-β stimulated clone-22) has been reported to induce differentiation, growth inhibition, and apoptosis in various cells. TSC-22 is a member of a family in which many proteins are produced from four different family genes. TSC-22 (corresponding to TSC22D1-2) is composed of 144 amino acids translated from a short variant mRNA of the TSC22D1 gene. In this study, we attempted to determine the intracellular localizations of the TSC22D1 family proteins (TSC22D1-1, TSC-22 (TSC22D1-2), and TSC22(86) (TSC22D1-3)) and identify the binding proteins for TSC22D1 family proteins by mass spectrometry. We determined that TSC22D1-1 was mostly localized in the nucleus, TSC-22 (TSC22D1-2) was localized in the cytoplasm, mainly in the mitochondria and translocated from the cytoplasm to the nucleus after DNA damage, and TSC22(86) (TSC22D1-3) was localized in both the cytoplasm and nucleus. We identified multiple candidates of binding proteins for TSC22D1 family proteins in in vitro pull-down assays and in vivo binding assays. Histone H1 bound to TSC-22 (TSC22D1-2) or TSC22(86) (TSC22D1-3) in the nucleus. Guanine nucleotide-binding protein-like 3 (GNL3), which is also known as nucleostemin, bound to TSC-22 (TSC22D1-2) in the nucleus. Further investigation of the interaction of the candidate binding proteins with TSC22D1 family proteins would clarify the biological roles of TSC22D1 family proteins in several cell systems.

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases, including oral cancer. Cancer cells usually escape from the immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα, in the tumor microenvironment of oral squamous cell carcinoma (OSCC), performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating to seven immune-related factors and several clinicopathological statuses. However, the immune checkpoint-related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that the keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference in tumor immunity in the originating epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC, might be different in the originating epithelium, keratinized or non-keratinized.

The involvement of oral bacteria in the pathogenesis of distant organs, such as the heart, lungs, brain, liver, and intestine, has been shown. We analyzed the distribution of bacterial species in the resected aortic valve by 16S rRNA metagenomic analysis and directly compared their gene sequences with those in the oral cavity. Thirty-two patients with aortic stenosis or aortic regurgitation who underwent aortic valve replacement were enrolled in this study. Antibody titer against periodontal pathogenic bacteria in the patient’s serum was analyzed. The genetic background and distribution of bacterial species on subgingival plaque, the dorsal surface of the tongue, and the resected aortic valve were analyzed. Patients with aortic valve disease were shown to have more severe periodontal disease by the detection of antibodies against Socransky’s red-complex bacteria of periodontitis. Bacterial DNA was detected in the aortic valves of 12 out of 32 patients. The genomic sequences of the V3-V4 region of the 16S rRNA in some bacteria isolated from the aortic valves of six patients who underwent metagenomic analysis were identical to those found in the oral cavity. The findings indicate that bacteria detected in the aortic valve may be introduced through oral dysbiosis, a condition characterized by an imbalance in the oral microbiota that increases the risk of periodontal disease and dental caries. Oral dysbiosis and the resulting potential bacteremia are associated with the pathogenesis of aortic valve diseases.

Background: Dental professionals were thought to have the most significant risk of coronavirus infection during the pandemic. Since the first Coronavirus Disease 2019 (COVID-19) patient was detected in Japan in January 2020, Japan has faced several waves of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections. However, no cluster of SARS-CoV-2 infections associated with dental procedures has been reported in Japan. In this study, we aimed to investigate the actual status of SARS-CoV-2 infection during the pandemic through antibody testing for dental professionals. We further investigated saliva and oral management-related aerosol to estimate the risk of virus transmission during dental procedures. Methods: SARS-CoV-2 antibody titer in the blood of dental professionals and their families was determined during the pre-vaccinated period of the SARS-CoV-2 wave to see the history of infection in Japan. Viral loads in saliva and in the aerosol generated during the oral management of COVID-19 patients were detected by RT-qPCR. Results: The antibody testing of dental healthcare providers during the early phases of the pandemic in Japan revealed low antibody positivity, which supported the low incidence of infection clusters among dental clinics. The aerosol generated during dental procedures may contain trace levels of SARS-CoV-2, indicating the risk of transmission through dental procedures is limited. Therefore, SARS-CoV-2 did not spread through dental clinics. Conclusions: Very few SARS-CoV-2 infections were observed in dental professionals who took appropriate infection control measures in the early period of the pandemic. Performing dental procedures using standard precautions seems to be sufficient to prevent SARS-CoV-2 infections.

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases including oral cancer. Cancer cells usually escape from immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα in the tumor microenvironment of oral squamous cell carcinoma (OSCC), and performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating seven immune-related factors and several clinicopathological statuses. However, the immune-checkpoint related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference of the tumor immunity in the originating-epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC might be different in the originating-epithelium, keratinized or non-keratinized.