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Background: We recently described the tumor immune microenvironment (TIME) in oral squamous cell carcinomas (OSCC) from Sudan by assessing the core of the lesions. However, the invasive tumor front (ITF) is the most active part of OSCC lesions; thus, TIME should also be characterized at the ITF in this patient cohort. Objectives: We aimed to evaluate patterns of immune cell infiltration at the ITF in a cohort of OSCC patients from Sudan previously investigated at the tumor center and their association with clinicopathological parameters. Methods: This study was performed on a prospective cohort of 22 OSCC patients attending Khartoum Dental Teaching Hospital with a median follow‐up of 48 months. Inflammatory infiltrate densities of CD4‐, CD8‐, FoxP3‐, CD20‐, CD66b‐, M1 (CD80/CD68)‐, M2 (CD163/CD68)‐, and PD‐L1‐positive cells were assessed at the ITF by immunohistochemistry, followed by digital quantitative analysis at the stromal and epithelial compartments separately. Histopathological parameters such as the worst pattern of invasion, differentiation, and tumor budding (TB) were also assessed. Correlations between clinicopathological parameters and survival analysis were investigated using SPSS. Results: All inflammatory cell subsets investigated were found to be higher in the stromal compartment as compared to the epithelial one, except for the PD‐L1+ subset. Stromal infiltration with the CD8+ cell subset was associated with low TB. Kaplan–Meier analyses identified higher epithelial and stromal CD4+ cell subsets. The presence of PD‐L1 was found to be associated with unfavorable overall survival. Further, Cox's regression analysis using an age‐ and tumor‐stage‐adjusted model identified epithelial PD‐L1 expression at the ITF as the only independent prognosticator. Conclusions: Epithelial PD‐L1 expression at the ITF was found to be an independent prognostic biomarker for OSCC in a cohort of Sudanese patients. [ABSTRACT FROM AUTHOR]

Background: Microbial dysbiosis and microbiome-induced inflammation have emerged as important factors in oral squamous cell carcinoma (OSCC) tumorigenesis during the last two decades. However, the "rare biosphere" of the oral microbiome, including fungi, has been sparsely investigated. This study aimed to characterize the salivary mycobiome in a prospective Sudanese cohort of OSCC patients and to explore patterns of diversities associated with overall survival (OS). Materials and Methods: Unstimulated saliva samples (n = 72) were collected from patients diagnosed with OSCC (n = 59) and from non-OSCC control volunteers (n = 13). DNA was extracted using a combined enzymatic–mechanical extraction protocol. The salivary mycobiome was assessed using a next-generation sequencing (NGS)-based methodology by amplifying the ITS2 region. The impact of the abundance of different fungal genera on the survival of OSCC patients was analyzed using Kaplan–Meier and Cox regression survival analyses (SPPS). Results: Sixteen genera were identified exclusively in the saliva of OSCC patients. Candida , Malassezia , Saccharomyces , Aspergillus , and Cyberlindnera were the most relatively abundant fungal genera in both groups and showed higher abundance in OSCC patients. Kaplan–Meier survival analysis showed higher salivary carriage of the Candida genus significantly associated with poor OS of OSCC patients (Breslow test: p = 0.043). In contrast, the higher salivary carriage of Malassezia showed a significant association with favorable OS in OSCC patients (Breslow test: p = 0.039). The Cox proportional hazards multiple regression model was applied to adjust the salivary carriage of both Candida and Malassezia according to age (p = 0.029) and identified the genus Malassezia as an independent predictor of OS (hazard ratio = 0.383, 95% CI = 0.16–0.93, p = 0.03). Conclusion: The fungal compositional patterns in saliva from OSCC patients were different from those of individuals without OSCC. The fungal genus Malassezia was identified as a putative prognostic biomarker and therapeutic target for OSCC. [ABSTRACT FROM AUTHOR]