Search Results (1,585)

Background/Objectives: Oral tongue squamous cell carcinoma (OTSCC) remains clinically challenging because conventional clinicopathological markers do not fully explain variability in recurrence and survival. This systematic review and functional meta-synthesis aimed to identify and critically appraise studies using preoperative magnetic resonance imaging (MRI)-based radiomics, artificial intelligence (AI), deep learning, or quantitative MRI-derived models to predict recurrence and prognostic outcomes in OTSCC. Methods: PubMed, Scopus, and Embase were searched from inception to March 2026. Eligible studies included prognostic model investigations in adults with OTSCC or primary tongue cancer without reported base-of-tongue/oropharyngeal involvement, undergoing preoperative MRI and surgery, with recurrence- or survival-related follow-up. The primary synthesis was a functional meta-synthesis; pooling was not performed because studies were not sufficiently comparable. Results: Seven retrospective studies were included, with a summed descriptive sample of 1287 participants. The evidence base was heterogeneous in MRI sequences, segmentation workflows, model architecture, validation strategy, and endpoint definition. Functional meta-synthesis identified four domains: direct recurrence-oriented modeling, broader prognostic stratification, reported incremental or complementary value over clinical frameworks, and translational maturity/technical implementation. Several studies reported associations between MRI-derived signatures and recurrence- or survival-related outcomes, but findings were interpreted narratively because of differences in primary endpoints, imaging features, model design, validation methods, and outcome definitions. Most studies were judged at high overall risk of bias, and certainty of evidence ranged from low to very low. Conclusions: MRI-based radiomics and AI show preliminary promise for prognostic stratification in OTSCC, particularly recurrence-related risk refinement, but current evidence remains limited by retrospective design, heterogeneity, sparse external validation, and low certainty. Full article

Background: Late-stage presentation of oral cancer remains a major challenge in low- and middle-income countries and contributes substantially to poor clinical outcomes. Data describing oral cancer presentation patterns in Indonesia remain limited. This study aimed to characterize the clinicopathological profile, stage distribution, treatment patterns, and exposure-related characteristics of oral cancer patients treated at a national referral center in Indonesia. Methods: A retrospective study was conducted using medical records of 404 patients with histopathologically confirmed oral malignancies treated between 2021 and 2025. Descriptive analyses were performed to summarize demographic, clinicopathological, staging, treatment-related, and exposure-related characteristics. Results: The mean age at diagnosis was 49.17 ± 14.11 years, with a relatively balanced sex distribution. The tongue was the most common primary tumor site (76.0%), and oral squamous cell carcinoma (OSCC) represented the predominant histopathological diagnosis (81.9%). Late-stage presentation (stage III–IV) was observed in 64.1% of all cases and increased to 70.7% among patients with available staging information, while 29.2% of patients had incomplete or undefined staging data. Surgical treatment, either alone or combined with adjuvant therapies, was the most frequently employed treatment modality. Notably, 21.5% of patients had no documented definitive oncologic treatment during the recorded treatment period. Smoking was reported by 35.4% of patients, alcohol consumption by 4.0%, and a family history of cancer by 24.8%. Conclusions: Advanced-stage oral cancer was highly prevalent in this referral-based cohort. The substantial burden of late-stage disease, together with incomplete staging information and the proportion of patients without documented definitive treatment, highlights challenges related to staging completeness, treatment documentation, and cancer care monitoring. These findings support efforts to strengthen early detection, referral coordination, and cancer care monitoring within the Indonesian healthcare system. Full article

Background/Objectives: Oral potentially malignant disorders (OPMDs) require accurate risk stratification to identify patients at the highest risk for severe oral epithelial dysplasia (OED) or oral squamous cell carcinoma (OSCC). We developed and internally validated the oral cancer numerical index (OCNI), a quantitative risk score derived from clinical features and deep learning-based brush cytology measurements. Methods: This retrospective model development and internal validation study was conducted using data from the multicenter Grand Opportunity study. Prospectively recruited subjects with OPMD with complete data were divided at the subject level into a training set (n = 384) and a holdout test set (n = 164) using a 70:30 diagnosis-stratified split. The primary endpoint was severe OED or OSCC versus benign diagnoses, and mild and moderate OED. Predictors included age, sex, tobacco history, lesion color, lesion size, multiple lesions, ulcerative morphology, and the percentages of differentiated squamous epithelial and small round cells derived from deep learning-based cytology. Prespecified rule-out and rule-in thresholds were selected in the training set to target 90% sensitivity and 90% specificity, respectively, and then applied to the holdout test set. Results: At the prespecified rule-out threshold (OCNI ≤ 37.6), sensitivity was 92% and negative predictive value was 97%. At the rule-in threshold (OCNI > 60.0), specificity was 89% and positive predictive value was 67%. Calibration was good in the holdout set (intercept, −0.07; slope, 1.13; Hosmer–Lemeshow p = 0.36), and OCNI increased significantly with worsening histopathologic severity. Conclusions: OCNI provided an objective, clinically interpretable estimate of risk for severe OED or OSCC, with strong rule-out and rule-in performance and good calibration. These findings support further external validation of OCNI as an adjunctive tool for oral lesion risk stratification. Full article

Background and objectives: Sentinel lymph node biopsy (SLNB) has become the standard approach for cervical staging in patients with early-stage oral cavity squamous cell carcinoma (OCSCC). Although it demonstrates diagnostic accuracy exceeding 90% in referral centres, the occurrence of false-negative (FN) results undermines oncological safety and adversely impacts patient prognosis. This scoping review aims to synthesise and evaluate the scientific evidence regarding the risk factors and technical errors that underpin FN incidence. Methods: A systematic search was conducted across MEDLINE (PubMed), Scopus and Web of Science for studies published between 2000 and 2025, adhering to PRISMA-ScR guidelines. Primary clinical and observational studies specifically addressing the variables and aetiology of diagnostic failure in SLNB for early-stage OCSCC (cT1-T2 N0) were included. Results: Twenty-seven studies were included in the final qualitative synthesis. Four critical domains characterising FN risk were elucidated, facilitating risk-stratified selection and surveillance strategies: (1) Clinical and tumour factors: Depth of invasion >4–5 mm, T3–T4 tumour size, and prior cervical anatomical disruption. (2) Surgical factors: Insufficient sentinel lymph node (SLN) harvest (≤2 SLNs), lack of exhaustive lymphatic basin exploration, the initial learning curve, and the exclusive use of non-isotopic tracers. (3) Anatomical factors: Floor of the mouth tumours and the radioactive shine-through effect. (4) Histopathological protocol: Suboptimal ultrastaging, insufficient frozen section biopsy, and limitations in rapid molecular techniques. Overall, studies using standardised protocols report a false-negative rate between 5% and 15%. Conclusions: FN events in SLNB are multifactorial and predictable phenomena, arising from cumulative vulnerabilities along the diagnostic continuum. The technique achieves an optimal diagnostic yield in cT1–T2 N0 cases without prior cervical treatment when applied under optimal conditions. However, methodological heterogeneity in the literature limits the interpretation of the results and partially constrains their clinical application. Full article

Background/Objectives: In Taiwan, more than 50% of patients with oral cancer seek medical help at a late stage. Reliable non-invasive biomarkers for pathological staging and disease monitoring are still lacking. This study aimed to identify a specific biomarker associated with late-stage oral cancer and to develop a non-invasive strategy for early pathological diagnosis and disease monitoring with improved patient acceptability. Methods: A total of 116 participants were enrolled, including 31 patients with early-stage oral cancer, 49 with late-stage oral cancer, and 36 healthy controls. Saliva samples were collected for proteomic analysis, and the findings were validated using ELISA and tissue immunohistochemistry. The identified biomarker was validated, and its tumor-promoting role was confirmed using malignant phenotype assays, including colony formation, soft agar, migration, and invasion assays. Results: Our results demonstrate that CD5L expression could not be distinguished between early- and late-stage groups using tissue immunohistochemistry. In contrast, salivary CD5L levels differentiated early-stage from late-stage patients noninvasively. Functional studies demonstrated that CD5L suppression markedly attenuated malignant phenotypes (colony formation, anchorage-independent growth, migration, invasion), suggesting its involvement in tumor aggressiveness and metastatic potential. Conclusions: These findings provide new insights into the pathological role of salivary CD5L in oral cancer progression and support its potential as a non-invasive biomarker for disease stratification. Full article

Background: Oral squamous cell carcinoma (OSCC) remains a major public health challenge, particularly in South Asian populations where environmental exposures such as tobacco and areca nut consumption contribute significantly to disease burden. Although genomic studies have improved understanding of oral cancer biology, population-specific genomic data from high-risk Indian populations remain limited. This study aimed to characterize the genomic landscape of OSCC using whole-exome sequencing (WES) of fresh biopsy specimens obtained from patients residing along the southwest coast of Karnataka, India. Methods: Paired tumor and adjacent normal tissues from ten OSCC samples (total n = 20 samples) were subjected to WES to identify somatic and germline-associated variants. Matched tumor–normal comparative analysis, variant annotation, and population frequency assessment using established genomic databases, including gnomAD, were performed to characterize the mutational profile. The findings were further compared with a previously analyzed regional cohort comprising 66 OSCC patients to evaluate recurrence patterns and population relevance. Results: The analysis identified a broad background of recurrent germline-associated variants alongside a comparatively limited number of tumor-specific somatic mutations, consistent with the expected predominance of constitutional genetic variation relative to acquired coding alterations in tumor samples. Recurrent variants were observed in genes associated with DNA repair, immune signaling, inflammatory responses, and pharmacogenomic pathways, including XRCC1, ITPKB, ABCB1, and OPRM1, whereas somatic alterations were primarily detected in established cancer-associated genes such as TP53, CDKN2A, and TERT. Conclusions: Several recurrent variants demonstrated high frequencies in South Asian populations, suggesting that they may represent recurrent population-associated variants of potential biological or pharmacogenomic relevance that require validation in larger cohorts. KEGG pathway enrichment analysis identified pathways related to cancer, chemical carcinogenesis, metabolic regulation, and xenobiotic response. Overall, these findings provide preliminary insights into the population-specific genomic characteristics of OSCC in this regional cohort and highlight the need for larger validation studies to determine the biological significance and reproducibility of these findings. Full article

Background: The oral squamous cell carcinoma (OSCC) is a very aggressive cancer that is the product of tumor cell interactions with the microenvironment. The tumor microenvironment (TME) has a severe impact on OSCC progression, metastasis, and resistance to treatment by altering gene expression via various cellular and molecular signal transductions. Aim: This review systematizes the information on gene regulation in the OSCC TME (cellular components, signaling pathways that regulate tumor progression and resistance). Methods: We used PRISMA guidelines to search PubMed, Scopus, Web of Science, and Google Scholar (up to April 2025) with OSCC studies addressing the subject of gene regulation and tumor microenvironment. The quality of human or experimental models was evaluated using the Newcastle–Ottawa Scale and the qualitative synthesis was performed because of heterogeneity. Results: The significant regulatory functions of tumor-associated macrophages, cancer-associated fibroblasts, immune cells, and non-coding RNAs were found, especially in the pathways like JAK/STAT, EGFR, Wnt/ -β catenin, and PI3K/AKT/mTOR. Conclusions: The conceptualization of gene regulatory networks in the OSCC TME identifies the emerging biomarkers and targets of therapy. Merging multimodal omics and single-cell studies can further contribute to the precision strategies to enhance the outcomes of OSCC. Full article

Salivary aldehyde dehydrogenases (ALDHs), particularly ALDH3A1, are increasingly recognized as potential contributors to oral defense against aldehyde-associated stress at the oral–environment interface. Unlike freely secreted salivary enzymes, measurable salivary ALDH activity primarily reflects intracellular and vesicle-associated enzymes derived from salivary gland epithelial cells, oral mucosal cells, immune cells, and exfoliated cellular components. Within the oral exposome, ALDHs expressed in oral epithelial and salivary gland tissues participate in the detoxification of reactive aldehydes, while salivary ALDH activity may serve as an indicator of local aldehyde-detoxification capacity and tissue redox status. Beyond aldehyde metabolism, emerging evidence suggests that ALDH-associated pathways are linked to redox regulation, epithelial stress adaptation, inflammatory signaling, and tissue repair through NAD(P)⁺-dependent processes and stress-responsive networks such as Nrf2 and SIRT1. This review provides a saliva-focused synthesis of ALDH biology, emphasizing isoform-specific functions and the potential importance of ALDH3A1 in oral epithelial defense. Altered salivary ALDH activity has been reported in association with oral conditions including periodontitis, oral lichen planus, radiation-induced salivary dysfunction, and oral squamous cell carcinoma (OSCC). Genetic factors, particularly ALDH2 polymorphisms, together with environmental exposures and microbial dysbiosis, may further influence aldehyde burden and oral disease susceptibility. Although current evidence supports the biological relevance of salivary ALDHs, their utility as clinical biomarkers or therapeutic targets remains investigational and requires further mechanistic and clinical validation. Full article

Background/Objectives: Behçet’s disease is a chronic relapsing multisystem inflammatory disorder characterized by recurrent mucocutaneous ulceration, vasculitis, and exaggerated inflammatory responses to minor trauma. These features may adversely affect wound healing after major head and neck oncologic reconstruction. This case report describes repeated wound breakdown after oral cavity reconstruction in a patient with Behçet’s disease and advanced floor-of-mouth squamous cell carcinoma. Methods: A 51-year-old woman with Behçet’s disease and T4N2bM0 squamous cell carcinoma involving the floor of the mouth and tongue underwent tumor resection followed by reconstruction of the oral cavity defect using a right anterolateral thigh perforator free flap. Subsequent surgical procedures included debridement of necrotic tissue, negative-pressure wound therapy, split-thickness skin grafting of the thigh donor site, and salvage tumor resection with pectoralis major myocutaneous flap reconstruction after tumor recurrence. Results: After the initial anterolateral thigh free flap reconstruction, flap perfusion was satisfactory in the immediate postoperative period; however, delayed marginal necrosis developed from the distal tongue-side flap margin, whereas the floor-of-mouth portion remained relatively stable. The right thigh donor site also developed progressive suture-line necrosis and wound dehiscence, requiring operative debridement, negative-pressure wound therapy, and split-thickness skin grafting. Although skin grafting achieved eventual donor-site coverage, partial graft necrosis and delayed secondary healing occurred. Persistent fistula and wound instability delayed postoperative radiotherapy, and recurrent floor-of-mouth squamous cell carcinoma subsequently developed approximately 6 months after the initial surgery. After salvage resection and pectoralis major myocutaneous flap reconstruction, the flap appeared viable at inset, but marginal ecchymosis, partial necrosis, and wound dehiscence again developed, requiring additional debridement, quilting sutures, and negative-pressure wound therapy. The wound gradually stabilized with staged wound management. Conclusions: This case illustrates a multifactorial pattern of repeated marginal wound breakdown after technically successful flap reconstruction in a patient with Behçet’s disease. Behçet-related pathergy-like inflammation, vasculitis, and microcirculatory dysfunction may represent possible contributing mechanisms, but they were not directly proven in this patient. In oral cavity reconstruction, such wound instability may delay adjuvant therapy and adversely affect oncologic outcomes. Careful perioperative planning, close multidisciplinary coordination, meticulous tension-free closure, early recognition of wound compromise, and readiness for staged wound management are essential in patients with Behçet’s disease undergoing major head and neck oncologic reconstruction. Full article

Background/Objectives: Intraoperative fluorescence imaging (FI) with tumor-targeted tracers offers a promising approach to improve surgical precision in cancer surgery. cRGD-ZW800-1, an integrin-targeted fluorescent tracer, has previously demonstrated safety, tumor specificity, and utility in detecting inadequate margins in oral cancer. During this study, we observed variability in background fluorescence between different subsites of the oral cavity. Therefore, this study aimed to systematically evaluate intraoperative in vivo and ex vivo mucosal contrast ratios across various oral cavity subsites using FI with cRGD-ZW800-1. Methods: Thirty-one patients with oral squamous cell carcinoma underwent intraoperative FI following intravenous injection of cRGD-ZW800-1 at least 18 h preoperatively. In vivo imaging was performed using the Quest Spectrum platform. In addition, ex vivo FI of the resected specimen was performed using the Pearl Trilogy Small Animal Imaging System. As these ex vivo images were obtained under uniform and controlled acquisition conditions, they allow for direct comparison with the intraoperative fluorescence signals. Fluorescence intensities and tumor-to-background ratios (TBRs) were assessed per oral subsite using manually drawn regions of interest (ROIs) on the tumor and adjacent healthy mucosa using Quest’s Spectrum Software, version 4.8.2, (in vivo images) and the Pearl’s integrated software ImageStudio version 6.2 (ex vivo images). A TBR ≥ 1.5 was considered sufficient. Results: Under uniform imaging settings, all samples exhibited adequate contrast (TBR ≥ 2.3), allowing clear tumor visualization and precise evaluation of mucosal margins on final histopathology. Notably, intraoperative in vivo contrast in the posterior located maxillary alveolar process was comparatively lower, which was attributable to suboptimal imaging conditions and subsite-specific background fluorescence. Conclusions: Our findings indicate that, although contrast varies across different oral subsites, all specimens exhibited sufficient ex vivo mucosal contrast to allow reliable tumor delineation. As in vivo imaging may be affected by subsite-specific background fluorescence and inherent limitations of intraoperative imaging geometry, fluorescence signals should be interpreted in conjunction with standard visual and tactile assessment. Due to anatomical constraints, different oral subsites may appear within the same field of view, which can influence perceived signal intensity. Therefore, intraoperative ex vivo fluorescence evaluation is recommended for signal interpretation. Full article

Oral squamous cell carcinoma (OSCC) represents a major global health burden, characterized by poor prognosis and limited improvement in survival over recent decades. Increasing evidence indicates that oral carcinogenesis is not solely driven by host genetic alterations but is significantly influenced by the oral microbiome through complex bidirectional interactions. This narrative review synthesizes current knowledge on the crosstalk between oral microbial communities and host genomic instability, with a specific focus on mutation-driven mechanisms. We discuss how microbial dysbiosis contributes to DNA damage, mutational signatures, epigenetic reprogramming, and immune modulation, thereby facilitating malignant transformation. Unlike previous reviews that address microbiome–cancer associations broadly, this work explicitly maps the mechanistic chain from microbial genotoxins through specific DNA repair pathway disruption to mutation accumulation in OSCC, and devotes substantial attention to the underexplored reverse direction—how host immune gene polymorphisms, DNA repair defects, and metabolic reprogramming shape the microbial niche. A comparative analysis with recent high-impact reviews is included. Finally, we outline emerging research directions, including multi-omics integration, single-cell and spatial transcriptomics, microbiome-targeted therapeutics, and artificial intelligence-assisted precision oncology approaches. Full article

Oral squamous cell carcinoma (OSCC) is characterized by consistently high mortality rates (≤60%) despite therapeutic advances. This is attributable to diagnostic delays arising from the asymptomatic early stages and time-consuming protocols. Hence, the establishment of reliable biomarkers for the routine assessment of the oral mucosa is imperative. MicroRNAs (miRNAs), key epigenetic regulators of gene expression, represent ideal candidates given their characteristic dysregulation across different pathologies. Here, we aimed to identify novel OSCC-specific miRNAs for the saliva-based detection of OSCC from the presymptomatic stage of early invasion. Through a multistep bioinformatic workflow, four miRNAs (miR-20b-5p, miR-484, miR-185-5p and miR-181d-5p) were identified as disease-specific since they simultaneously regulated >65% of a panel encompassing the 15 primarily overexpressed oncogenes in OSCC and a stage-specific panel including the six upregulated genes that genetically define the malignant stages of sequential oral carcinogenesis. The salivary expression of the identified miRNAs was studied in 31 OSCC patients and 31 healthy controls, using quantitative real-time PCR, followed by statistical analysis and an evaluation of the diagnostic accuracy. All studied miRNAs were significantly downregulated in the saliva of OSCC patients compared to controls (miR-484, p < 0.001; miR-181d-5p, p < 0.001; miR-185, p = 0.008; miR-20b, p = 0.026) and exhibited combinatory diagnostic performance of 95.4% (p < 0.001) for OSCC detection. Their expression remained uninfluenced by lifestyle and clinicopathological parameters, including smoking/alcohol, tumor site, grade and disease stage. The proposed 4-miRNA panel exhibits high diagnostic performance for the early, saliva-based detection of OSCC, irrespective of histopathological and lifestyle confounders, highlighting its potential as a robust non-invasive screening tool. Full article

Background: Reliable assessment of cervical lymph node metastases remains a key challenge in the management of oral squamous cell carcinoma (OSCC). While elective ipsilateral neck dissection (ND) is widely accepted, the benefit of contralateral ND and the influence of tumor site on metastatic risk remain incompletely defined. This study aimed to evaluate patterns of lymphatic metastases, the diagnostic accuracy of preoperative staging, and the therapeutic relevance of ipsilateral and contralateral ND. Methods: A retrospective single-center cohort study was conducted including 287 patients with histologically confirmed OSCC treated between 2013 and 2019. Patterns of lymph node metastases were analyzed with respect to tumor localization and clinicopathological factors. Multivariate binary logistic regression was performed to identify predictors of cervical lymph node metastases. The diagnostic accuracy of preoperative staging was evaluated using histopathological findings as the reference standard. Results: Tumor localization and histopathological grading significantly influenced the occurrence of lymph node metastases. OSCC of the maxilla demonstrated a significantly lower observed rate of cervical and occult metastases compared with other tumor sites. Occult metastases were detected in 16.9% of primary tumor cases, with only two contralateral occult metastases observed. The calculated number needed to treat (NNT) was 6 for ipsilateral elective ND and 74 for contralateral elective ND. Preoperative staging showed limited diagnostic accuracy, with a negative predictive value of 0.83 and a positive predictive value of 0.65. Conclusions: Elective ipsilateral ND remains an essential component in the surgical management of OSCC due to the considerable rate of occult metastases and the limited reliability of preoperative staging. In contrast, the benefit of contralateral elective ND appears limited in patients without midline-crossing tumors. Maxillary OSCC and well-differentiated tumors demonstrated a significantly lower metastatic risk, supporting a more individualized risk-adapted approach to neck dissection in selected cases. Full article

Head and neck squamous cell carcinoma (HNSCC) remains an immunosuppressive and metabolically dysregulated malignancy, contributing to tumor progression and resistance to conventional therapies. Natural compounds offer a unique multi-target opportunity to address these challenges, with berry-derived phytochemicals emerging as particularly promising candidates. Preclinical evidence demonstrates that these compounds modulate dendritic cell activation, macrophage polarization, regulatory T cell function, and cytokine signaling, restoring immune balance while simultaneously regulating tumor metabolism and reducing chronic inflammation. Beyond these immunometabolic effects, berry-derived compounds influence glucocorticoid signaling at the endocrine–immune interface, alleviating additional immunosuppressive pressures within the tumor microenvironment. Early clinical studies support the feasibility of standardized berry-derived formulations as adjunctive agents. In patients with oral premalignant lesions and HNSCC, black-raspberry-based interventions including topical gels and oral troches, have demonstrated favorable safety profiles, measurable tissue uptake of bioactive phytochemicals, modulation of proliferation and inflammation-associated biomarkers (e.g., Ki-67, COX-2, and NF-κB), and partial histologic regression in a subset of lesions. Collectively, these pleiotropic actions highlight chemopreventive potential and provide a mechanistic rationale for combinatorial strategies with immune checkpoint inhibitors targeting PD-1/PD-L1 and CTLA-4. Opportunities for both local and systemic delivery may further enhance therapeutic efficacy. Integrating these natural compounds into precision chemoprevention and immunotherapy paradigms could inform rational drug discovery, biomarker-driven patient stratification, and combination therapy design. This review highlights the convergent immunologic, metabolic, and endocrine-targeted mechanisms of berry-derived phytochemicals in HNSCC and emphasizes their translational potential as integrative modulators of antitumor immunity. Full article

Oral squamous cell carcinoma (OSCC) shows substantial immune and clinical heterogeneity that is not fully captured by conventional clinicopathologic risk factors. This systematic review synthesized primary studies evaluating immune biomarker signatures in OSCC identified through spatial transcriptomics, single-cell transcriptomics, and artificial intelligence (AI)-enabled pathology. PubMed/MEDLINE, Scopus, and Embase were searched without language or date restrictions. Eligible studies included original human OSCC investigations reporting immune-relevant biomarker outputs derived from spatial/single-cell transcriptomics or AI-enabled pathology. Nine studies met the inclusion criteria. Six used spatial and/or single-cell transcriptomic approaches, and three used AI-enabled pathology applied to histopathological whole-slide images. Functional meta-synthesis identified four interconnected domains: AI-derived tissue immune infiltration for prognostic stratification; T-cell states and tertiary lymphoid structure-associated antitumor immunity; spatial and metabolic immunosuppressive niches; and stromal–myeloid programs linked to T-cell exhaustion and resistance. Quantitative synthesis was considered but not performed because no group of studies was sufficiently comparable in biomarker construct, comparator, outcome, and effect measure. Clinical confidence remains limited by heterogeneity and prospective validation gaps. These findings suggest that emerging OSCC immune biomarkers may integrate tissue architecture, cellular states, and stromal–immune interactions; however, the current evidence remains exploratory and requires standardized, prospective validation before clinical translation can be considered. Full article