Factors influencing delayed referral of oral cancer patients from family dentists to the core hospital.

Background/purpose: Most oral cancer (OC) cases are identified by family dentists in Japan. However, a significant number of patients with OC in Japan are referred to core hospitals at advanced stages. Therefore, identifying the factors that contribute to delayed referrals from family dentists to core hospitals is crucial for detecting OC in its earlier stages. The aim of this retrospective study was to identify the risk factors for referral delays from family dentists to core hospitals. Materials and methods: The study included 63 patients with OC who were referred by family dentists to the Yamagata University Hospital between 2010 and 2022. The clinical parameters related to referral delays were retrospectively investigated using letters of reference provided by the family dentists and patient charts. Backward multiple regression analysis was performed to identify the relationships between the length of referral delay and potential risk factors. Additionally, backward multivariate logistic regression analysis was performed to examine the independent association between referral delays of >4 weeks and several clinical parameters. Results: Multiple regression analysis revealed that misdiagnosis of malignant lesions by family dentists (P = 0.047) was significantly associated with longer referral delays. Additionally, misdiagnosis of malignant lesions by family dentists was also an independent risk factor for referral delays of >4 weeks (odds ratio, 10.387; P = 0.006). Conclusion: Misdiagnosis of malignant lesions by family dentists was a significant risk factor for referral delays from family dentists to core hospitals. Our results will motivate family dentists to improve their ability to diagnose OC.

Expression of PVRL4, a molecular target for cancer treatment, is transcriptionally regulated by FOS.

PVRL4 (or nectin­4) is a promising therapeutic target since its upregulated expression is found in a wide range of human cancer types. Enfortumab vedotin, an antibody­drug conjugate targeting PVRL4, is clinically used for the treatment of urothelial bladder cancer. In addition, rMV­SLAMblind, a genetically engineered oncolytic measles virus, can infect cancer cells and induce apoptosis through interaction with PVRL4. Although PVRL4 transcript levels are elevated in breast, lung and ovarian cancer, the mechanisms of its upregulation have not yet been uncovered. To clarify the regulatory mechanisms of elevated PVRL4 expression in breast cancer cells, Assay for Transposase­Accessible Chromatin­sequencing and chromatin immunoprecipitation­sequencing (ChIP­seq) data were used to search for its regulatory regions. Using breast cancer cells, an enhancer region was ultimately identified. Additional analyses, including ChIP and reporter assays, demonstrated that FOS interacted with the PVRL4 enhancer region, and that alterations of the FOS­binding motifs in the enhancer region decreased reporter activity. Consistent with these data, exogenous expression of FOS enhanced the reporter activity and PVRL4 expression in breast cancer cells. Furthermore, RNA­seq analysis using breast cancer cells treated with PVRL4 small interfering RNA revealed its possible involvement in the cytokine response and immune system. These data suggested that FOS was involved, at least partly, in the regulation of PVRL4 expression in breast cancer cells, and that elevated PVRL4 expression may regulate the response of cancer cells to cytokines and the immune system.