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The incidence of human papilloma virus–mediated oropharyngeal squamous cell carcinoma (OPSCC) has increased over the past 40 years, particularly among young individuals with a favorable prognosis; however, current therapy often leads to unfortunate side effects, such as dysphagia. Despite the emphasis on dysphagia in previous studies, there is an important research gap in understanding the correlation between neuronal changes and patient-reported and functional outcomes in patients with OPSCC. To address this issue, we examined pathologic tissue samples from patients with OPSCC using multiplex immunofluorescence staining and machine learning to correlate tumor-associated neuronal changes with prospectively collected patient-reported and functional outcomes. We found that tumor enrichment of adrenergic (TH+) and CGRP+ sensory–afferent nerves correlated with poorer swallowing outcomes. Functional electromyography recordings showed correlations between growing (GAP43+) and immature cholinergic (ChAT+DCX+) nerves and denervation patterns in survivors of OPSCC. A murine model of radiation-induced dysphagia further confirmed that immature cholinergic and CGRP+ nerves were correlated with impaired swallowing. Preclinical interventional studies also supported the independent contributions of CGRP+ and cholinergic (ChAT+) nerves to dysphagia in treated mouse models of OPSCC. Our results suggest that CGRP+ and ChAT+ neuronal signaling play distinct roles in tumor- and radiation-induced dysphagia in OPSCC and offer a comprehensive dataset on the neural landscape of OPSCC. These insights may guide early interventions for swallow preservation and the repurposing of neurology-related drugs, such as CGRP blockers, in clinical oncology and survivorship. Editor's summary: Patients with human papilloma virus (HPV)–mediated oropharyngeal squamous cell carcinoma (OPSCC) often have a good prognosis; however, standard of care treatment often leads to poor side effects such as dysphagia. To better understand this link, Islam et al. evaluated patient sample neural landscapes and correlated these with patient outcomes. They saw that tumor enrichment of adrenergic and CGRP+ nerves correlated with worse swallowing outcomes. They further evaluated this mechanism in a mouse model and suggest that CGRP blockers may help preserve swallow function in patients; however, this will require further study. —Dorothy Hallberg [ABSTRACT FROM AUTHOR]

The sirtuins (SIRTs) are a family of highly conserved histone deacetylases (HDACs) consisting of seven members (SIRT1-SIRT7). Over the past few decades, SIRT1 has been the most extensively studied and garnered tremendous attention in the scientific community due to its emerging role in cancer biology. However, its biological role in the regulation of oral cancer is not yet fully understood. Owing to contradictory findings regarding the role of SIRT1 in oral cancer, debate about it continues. The present study discusses the biological roles and potential therapeutic implications of SIRT1 in precancerous oral lesions and oral cancer. [ABSTRACT FROM AUTHOR]

Background/aim: Cyclooxygenase is an enzyme that transforms arachidonic acid to prostaglandins. Cyclooxygenase-2 (COX-2) is an isoform of cyclooxygenase. There exist many reports on the expression levels of COX-2 in cancer tissues, and prognosis of cancer patients has been reported to be related to COX-2 up-regulation. In the present study we assessed the suppressive effect of AHCC ® on the expression of COX-2 in QRsP-11cells., Materials and Methods: QR-32 is a clone which was derived from murine fibrosarcoma BMT-11 cells by treatment with quercetin. These clone cells regress spontaneously after injection into C57BL/6 mice. QRsP-11 is a clone derived from QR-32, showing very aggressive tumorigenicity. AHCC ® is a standardized extract of cultured Lentinula edodes mycelia and has been reported to exert suppressive effects on various tumor-associated proteins including HSP27. The protein levels of COX-2 in QR-32 and QRsP-11 cells were compared by using western blotting. Furthermore, the expression levels of COX-2 were assessed in QRsP-11 cells after AHCC ® -treatment., Results: Western blot analysis showed a significant up-regulation of COX-2 in QRsP-11 cells compared to QR-32 cells. In vitro AHCC ® -treatment increased COX-2 expression levels in QRsP-11 cells contrary to expectations., Conclusion: When using AHCC ® in cancer treatment, it might be important to decrease COX-2 expression by means of non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin. Further studies are required to clarify the mechanism of up-regulation of COX-2 through AHCC ® -treatment., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)