BACKGROUND: Oral cancer (OC) is a common malignancy in clinical practice. Saliva testing is a convenient and noninvasive early diagnostic technique for OC. Several salivary cytokines have been identified as potential biomarkers for OC, including IL-8, IL-6, TNF-α, IL-1β, and IL-10. Nonetheless, the optimal cytokine for OC diagnosis remains inconclusive and highly contentious.
METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were comprehensively retrieved to collect all case-control studies on OC. A meta-analysis was performed to compare the levels of salivary IL-8, IL-6, IL-10, TNF-α, and IL-1β in OC patients and healthy controls. Network meta-analysis (NMA) was carried out to probe into the accuracy of these salivary cytokines in diagnosing OC.
RESULTS: This analysis included 40 studies, encompassing 1280 individuals with OC and 1254 healthy controls. Significantly higher levels of salivary IL-8, IL-6, TNF-α, IL-1β, and IL-10 were observed in patients with OC in comparison to healthy controls. The results of NMA showed that TNF-α had the highest diagnostic accuracy for OC, with a sensitivity of 79% and a specificity of 92%, followed by IL-6 (sensitivity: 75%, specificity: 86%) and IL-8 (sensitivity: 80%, specificity: 80%).
CONCLUSIONS: This study suggests that IL-8, IL-6, IL-10, TNF-α, and IL-1β may be potential diagnostic biomarkers for OC. Among them, TNF-α, IL-6, and IL-8 are highly accurate in the diagnosis of OC. Nevertheless, further studies that eliminate other confounding factors are warranted, and more standardized procedures and large-scale studies are needed to support the clinical use of saliva testing.

Prediction plays a ubiquitous role in cancer care. At every stage of the illness, the patient, the physician, and the family must make numerous decisions. Utilizing epidemiological, clinical, biological, lifestyle, and genetic factors, a cancer-specific risk assessment model calculates the likelihood of developing cancer. In India, oral cancer ranks as the fourth most common cancer, affecting nearly 3,000,00 individuals annually. Because it is in the premalignant stage, oral cancer is easily detectable in the oral cavity. Prompt identification of this lesion can result in better outcomes and a higher standard of living. Advanced statistical techniques have been used to develop prediction algorithms or risk scores that identify individuals with a high risk of developing oral cancer. With the aid of these risk assessment models, specific individuals can be screened to aid in the early detection of the disease, which may result in better outcomes and lifestyle modifications. Finding the best model among the current risk models for oral cancer may be aided by a thorough examination of all these models. Finding and assessing the risk model that primary care physicians can use and easily apply in clinical practice will be made easier with a succinct and straightforward comparison of the models. This review compares the current models to determine which has the best performance metrics, which could lead to a better understanding of the advantages and disadvantages of various risk prediction models of oral cancer.

OBJECTIVE: To compare the diagnostic accuracy of Contrast Enhanced Computed Tomography (CECT) compared to conventional imaging modalities and histopathological investigation in cervical lymph node metastasis in adults through a novel meta- analysis.
METHODS: The review protocol is registered under PROSPERO(CRD42021225704) and performed in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analysis - Diagnostic Test Accuracy (PRISMA- DTA) checklist. Databases like PubMed, Google Scholar, EBSCOhost were searched from 2000 to 2023 to identify the diagnostic potential of CECT in cervical lymph node metastasis of oral carcinoma. True-positive, false-positive, true-negative, false-negative, sensitivity, specificity values were extracted or calculated if not present for each study. Quality of selected studies was evaluated based on Quality assessment of diagnostic accuracy studies (QUADAS)- 2 tool. Meta-analysis was performed in Meta-Disc 1.4 software and Review Manager 5.3 using a bivariate model parameter for the pooled sensitivity and pooled specificity. Additional analysis was performed in terms of positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR) and summary receiver operating characteristics (SROC) with Area Under Curve (AUC) and p<0.05 as statistically significant.
RESULTS: Six studies were included for qualitative synthesis and as well as for meta-analysis. Two studies had high risk of bias while four studies had low risk of bias. 651 patients underwent CECT and were taken for meta-analysis. The meta-analysis revealed that CECT for diagnosing cervical lymph node metastasis had a pooled sensitivity of 71%, pooled specificity of 14% with 60% Area Under Curve (AUC). +LR of 0.84, -LR of 1.36 and DOR of 0.59.
CONCLUSIONS: CECT has an overall fair diagnostic ability and is a valid and reliable tool in diagnosing the target condition overcoming high reliance on master specialized capacity for their execution and understanding like other conventional imaging techniques. CECT can be concluded for secondary level of prevention for cervical node metastasis of oral carcinoma under early diagnosis and prompt treatment. However, further standardized accuracy studies are indicated to improve the overall diagnostic accuracy of CECT.

OBJECTIVE: To summarize and compare the existing evidence on diagnostic accuracy of artificial intelligence (AI) models in detecting early oral squamous cell carcinoma (OSCC).
METHODS: Review was performed in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analysis - Diagnostic Test Accuracy (PRISMA- DTA) checklist and the review protocol is registered under PROSPERO(CRD42023456355). PubMed, Google Scholar, EBSCOhost were searched from January 2000 to November 2023 to identify the diagnostic potential of AI based tools and models. True-positive, false-positive, true-negative, false-negative, sensitivity, specificity values were extracted or calculated if not present for each study. Quality of selected studies was evaluated based on QUADAS (Quality assessment of diagnostic accuracy studies)- 2 tool. Meta-analysis was performed in Meta-Disc 1.4 software and Review Manager 5.3 RevMan using a bivariate model parameter for the sensitivity and specificity and summary points, summary receiver operating curve (SROC), diagnostic odds ratio (DOR) confidence region, and area under curve (AUC) were calculated.
RESULTS: Fourteen studies were included for qualitative synthesis and for meta-analysis. Included studies had presence of low to moderate risk of bias. Pooled sensitivity and specificity of 0.43 (CI 0.18- 0.71) and 0.50 (CI 0.20- 0.80) was observed with a pooled positive likelihood ratio of (PLR) 0.86 (0.43 - 1.71) and negative likelihood ratio (NLR) of 1.04 (0.42 - 1.68) was observed with DOR of 0.78 (0.12 - 5.18) and overall accuracy (AUC) being 0.45 respectively.
CONCLUSIONS: AI based tools has poor to moderate overall diagnostic accuracy. However, to validate our study findings further more standardized diagnostic accuracy studies should be conducted with proper reporting through QUADAS-2 tool. Thus, we can conclude AI based based tool for secondary level of prevention for early OSCC under early diagnosis and prompt treatment.

Oral cancer is a disease with high mortality and rising incidence worldwide. Although fragmentary literature on the anti-oral cancer effects of plant products has been published, a comprehensive analysis is lacking. In this work, a critical and comprehensive evaluation of oral cancer preventative or therapeutic effects of dietary plants was conducted. An exhaustive analysis of available data supports that numerous dietary plants exert anticancer effects, including suppression of cell proliferation, viability, autophagy, angiogenesis, invasion, and metastasis while promoting cell cycle arrest and apoptosis. Plant extracts and products target several cellular mechanisms, such as the reversal of epithelial-to-mesenchymal transition and the promotion of oxidative stress and mitochondrial membrane dysfunction by modulation of various signaling pathways. These agents were also found to regulate cellular growth signaling pathways by action on extracellular signal-regulated kinase and mitogen-activated protein kinase, inflammation via modulation of cyclooxygenase (COX)-1, COX-2, and nuclear factor-κB p65, and metastasis through influence of cadherins and matrix metalloproteinases. In vivo studies support these findings and demonstrate a decrease in tumor burden, incidence, and hyperplastic and dysplastic changes. Clinical studies also showed decreased oral cancer risk. However, high-quality studies should be conducted to establish the clinical efficacy of these plants. Overall, our study supports the use of dietary plants, especially garlic, green tea, longan, peppermint, purple carrot, saffron, tomato, and turmeric, for oral cancer prevention and intervention. However, further research is required before clinical application of this strategy.

OBJECTIVE: This study aimed to provide a comprehensive assessment of the measurement and prevalence of betel-quid (BQ) abuse, dependence, and BQ use disorder (BUD), as well as to evaluate the impact of BQ addiction on oral malignant diseases.
METHODS: We used the PRISMA guidelines to perform a systematic review and meta-analysis. We searched for relevant publications up to April 2024 in PubMed, Web of Science, and Embase. The articles were evaluated for BQ addiction and its relationship with oral potentially malignant disorders (OPMD) and oral cancer.
RESULTS: The prevalence of BQ abuse, dependence, and BUD in South, Southeast, and East Asia varied between 0.8%-46.3%, 0.4%-43.5%, and 4.7%-39.2%, respectively. Among BQ chewers, the corresponding proportions of these disorders ranged from 40.5%-99.6%, 20.9%-99.6%, and 55.2%-99.3%. The pooled risks of OPMD associated with BQ abuse, dependence, and BUD were 16.3, 18.7, and 9.6-35.5, respectively. The risk of oral cancer for mild, moderate, and severe BUD was 8.5, 8.2, and 42.3, respectively.
CONCLUSIONS: BUD mediates the link between BQ use and an increased risk of oral malignant disorders. Addressing and treating BQ addiction is an important component of comprehensive OPMD and oral cancer preventive and intervention programs that go beyond simple cessation efforts.

To investigate the diagnostic and therapeutic potential of nanoparticle (NP)-based immunosensors in the field of oral cancer. PubMed, Embase, Scopus, Web of Science, and Google Scholar databases were explored for NP applications in oral cancer. Data extraction in terms and quality assessment of all the articles were done. Out of 147, 17 articles were included in this review. A majority of the studies showed improved sensitivity and specificity for saliva analysis using an enzyme-linked immunosorbent assay based on gold NPs, improving early identification. Additionally, novel therapeutic approaches, utilising NP-based immunosensors, demonstrated targeted drug delivery, coupled chemo-photothermal therapy, and gene silencing. Imaging methods have made it possible to distinguish between malignant and healthy states, such as surface-enhanced Raman scattering and optical coherence tomography. The reviews\' findings highlight the transformational potential of NP-based immunosensors in addressing the difficulties associated with diagnosing and treating oral cancer. However, for an accurate interpretation and application of NP-based solutions in clinical practise, it is essential to be thoroughly aware of the intricacies involved, and the synthesised data in this review support the continued investigation and improvement of NP-based therapies in the ongoing effort to improve the management of oral cancer.

More than 50% of oral cancer (OC) patients are diagnosed with advanced-stage disease associated with poor prognosis and quality of life, supporting an urgent need to improve early OC detection. The identification of effective molecular markers by minimally invasive approaches has emerged as a promising strategy for OC screening. This systematic review summarizes and evaluates the performance of the DNA methylation markers identified in non- or minimally invasive samples for OC detection. PubMed\'s MEDLINE, Scopus, Embase, and Cochrane Library databases were systematically searched for studies that evaluated DNA methylation markers in non-invasive and/or minimally invasive samples (oral rinse/saliva, oral brush, and blood) from OC patients. Two investigators independently extracted data on study population characteristics, candidate methylation markers, testing samples, DNA methylation assay, and performance diagnostic outcomes. Methodological study quality was assessed with the Quality Assessment for Studies of Diagnostic Accuracy-2 tool. Thirty-one studies met the inclusion criteria for this systematic review. DNA methylation markers were evaluated in oral rinse/saliva (n = 17), oral brush (n = 9), and blood (n = 7) samples. Methylation-specific PCR (MSP) and quantitative-MSP were the most common DNA methylation assays. Regarding diagnostic performance values for salivary, oral brush, and blood DNA methylation markers, sensitivity and specificity ranged between 3.4-100% and 21-100%, 9-100% and 26.8-100%, 22-70% and 45.45-100%, respectively. Different gene methylation panels showed good diagnostic performance for OC detection. This systematic review discloses the promising value of testing DNA methylation markers in non-invasive (saliva or oral rinse) or minimally invasive (oral brush or blood) samples as a novel strategy for OC detection. However, further validation in large, multicenter, and prospective study cohorts must be carried out to confirm the clinical value of specific DNA methylation markers in this setting.

Recently, microRNAs (miR) were identified to have potential links with oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) oncogenesis, specifically miR-21. Since HPV is a major risk factor for the development of these diseases, we aimed to search the literature regarding miR-21 expression in both HPV-positive and HPV-negative OSCC/OPSCC. The search was performed in the PubMed (MEDLINE), Scopus, Web of Science, and Cochrane electronic databases. The research question was as follows: Is there a difference in the tissue expression of miR-21 between patients with HPV-positive and those with HPV-negative OSCC/OPSCC? After conducting a meticulous search strategy, four studies were included, and they had a pooled sample size of 621 subjects with OSCC and/or OPSCC. Three studies did not find any significant difference in miR-21 expression between HPV-positive and HPV-negative OSCC/OPSCC. The findings of this systematic review showed that there are no differences in miR-21 expression between HPV-positive and HPV-negative OSCC/OPSCC. Nevertheless, it is worth noting that there are still insufficient studies regarding this important subject, because understanding how HPV influences miR-21 expression and its downstream effects can provide insights into the molecular mechanisms underlying OSCC/OPSCC development and progression.

We aimed to qualitatively and quantitatively analyze, through a systematic review and meta-analysis, the current evidence on the differential expression of the hallmarks of cancer in oral lichen planus (OLP) samples, in order to know the earliest molecular mechanisms that could be involved in the malignant transformation of this oral potentially malignant disorder. We searched MEDLINE/PubMed, Embase, Web of Science, and Scopus for studies published before November 2023. We evaluated the methodological quality of studies and carried out meta-analyses to fulfill our objectives. Inclusion criteria were met by 110 primary-level studies, with 7065 OLP samples, in which the expression of 104 biomarkers were analyzed through immunohistochemistry. Most OLP samples showed sustained cell proliferation signaling (65.48%, 95%CI = 51.87-78.02), anti-apoptotic pathways (55.93%, 95%CI = 35.99-75.0), genome instability (48.44%, 95%CI = 13.54-84.19), and tumor-promoting inflammation events (83.10%, 95%CI = 73.93-90.74). Concurrently, OLP samples also harbored tumor growth suppressor mechanisms (64.00%, 95%CI = 53.27-74.12). In conclusion, current evidence indicates that molecular mechanisms promoting hyperproliferative signaling, an antiapoptotic state with genomic instability, and an escape of epithelial cells from immune destruction, are developed in LP-affected oral mucosa. It is plausible that these events are due to the actions exerted by the chronic inflammatory infiltrate. Malignant transformation appears to be prevented by tumor suppressor genes, which showed consistent upregulation in OLP samples.