Different efforts have been made to find better and less invasive methods for the diagnosis and prediction of oral cancer, such as the study of saliva as a source of biomarkers. The aim of this study was to perform a scoping review about salivary molecules that have been assessed as possible biomarkers for the diagnosis of oral squamous cell carcinoma (OSCC). A search was conducted using EBSCO, PubMed (MEDLINE), Scopus, and Web of Science. The research question was as follows: which molecules present in saliva have utility to be used as biomarkers for the early detection of oral cancer? Sixty-two studies were included. Over 100 molecules were assessed. Most of the markers were oriented towards the early diagnosis of OSCC and were classified based on their ability for detecting OSCC and oral potentially malignant disorders (OPMDs), OSCC outcome prediction, and the prediction of the malignant transformation of OPMDs. TNF-α, IL-1β, IL-6 IL-8, LDH, and MMP-9 were the most studied, with almost all studies reporting high sensitivity and specificity values. TNF-α, IL-1β, IL-6 IL-8, LDH, and MMP-9 are the most promising salivary biomarkers. However, more studies with larger cohorts are needed before translating the use of these biomarkers to clinical settings.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is characterized by an immunosuppressive tumor microenvironment. Their plasma-derived exosomes deliver immunomodulatory molecules and cargo that correlate significantly with clinical parameters. This study aims to assess the exosomal profile as a potential tool for early detection of relapse and long-term outcomes in OSCC patients undergoing conventional therapy.
METHODS: 27 OSCC patients with a median 38-month follow-up were included in this study. The relationship between NTA-derived parameters and clinical pathological parameters was examined, and receiver operating characteristic (ROC) curves were utilized to evaluate the diagnostic efficacy of these values in detecting cancer relapse.
RESULTS: Plasmatic levels of exosomes prior to surgery showed a drastic reduction after surgical intervention (8.08E vs. 1.41 × 109 particles/mL, p = 0.006). Postsurgical concentrations of exosomes were higher in patients who experienced relapse compared to those who remained disease-free (2.97 × 109 vs. 1.11 × 109 particles/mL, p = 0.046). Additionally, patients who relapsed exhibited larger exosome sizes after surgery (141.47 vs. 132.31 nm, p = 0.03). Patients with lower concentrations of exosomes prior to surgery demonstrated better disease-free survival compared to those with higher levels (p = 0.012). ROC analysis revealed an area under the curve of 0.82 for presurgical exosome concentration in identifying relapse.
CONCLUSIONS: Presurgical exosomal plasmatic levels serve as independent predictors of early recurrence and survival in OSCC. All in all, our findings indicate that the detection of peripheral exosomes represents a novel tool for the clinical management of OSCC, with potential implications for prognosis assessment.

The gradual accumulation and inadequate renewal of senescent cells over time drive organismal aging. Senescent cells undergo altered gene expression and release inflammatory mediators collectively termed the senescence-associated secretory phenotype (SASP), which significantly contributes to a spectrum of age-related disorders, including cancer. In the context of carcinogenesis, the SASP produced by senescent cells has been implicated in the promotion of epithelial cancers, including oral squamous cell carcinoma (OSCC), the most common form of oral cancer. Senescent cells within the tumor microenvironment release factors that amplify the growth and invasiveness of neighboring cancer cells. Senotherapeutics, including senolytics and senomorphics, emerge as promising modalities to target senescent cells and their associated inflammatory factors, thereby opening novel avenues for augmenting the efficacy of cancer treatments. Here, we review the general aspects of cellular senescence, focusing on the relation between senescence-related inflammation with cancer development. We also analyze the available evidence linking cellular senescence with OSCC, highlighting possible clinical applications.

Head and neck cancer (HNC) is a major public health problem in India. This article presents the HNC burden in different regions of India. The published population-based cancer registries (PBCRs) data from the National Cancer Registry Programme, Bengaluru, and the Tata Memorial Centre, Mumbai, India, were utilised. The 37 PBCRs were divided into six regions including central, east, north, northeast, west and south. The age-standardised incidence rate of HNC was 25.9 (95% CI 25.7-26.1) and 8.0 (95% CI 7.9-8.1) per 100,000 population, respectively, in males and females. HNC accounted for about 26% of all cancer cases in males and 8% in females. The risk of developing HNC was 1 in 33 for males and 1 in 107 for females. The northeastern registries reported the highest incidence rate 31.7 per 100,000 population in males followed by northern (28.5), central (28.3), western (24.4), southern (23.9) and eastern (18.3). In females, the incidence was in the range of 6.2-10.1 per 100,000 population. For all PBCRs together, the HNC burden was two to three times higher in the age group 60+ as compared to 20-39 years. The HNC burden in India is higher than in the USA, UK, Australia, Africa and Brazil. The PBCRs from the south-east Asia region such as the Colombo district, Sri Lanka, as well as Siraha, Saptari, Dhanusha and Mohattari - Nepal have also reported a high burden of HNC. All regions reported mouth as a leading cancer site followed by tongue, larynx, hypopharynx and tonsil except the northeastern region registries where hypopharynx was the top leading cancer. The burden of other sites of HNC is low. Raising awareness of the disease and associated risk factors, providing early detection services, as well as easy access to diagnosis and treatment are required. The government should focus on building the infrastructure and capacity building to control this disease.

Late detection of oral cancer (OC) cases in Saudi Arabia is concerning. It reduces survival rate and complicates treatment. The ISAC intervention was developed to bridge the gaps observed in dentists\' practice of OC examination and patient education. The ISAC stands for I, informing patients of OC screenings; S, screening for OC; A, advising high-risk patients to quit risk factors; and C, connecting patients to advanced services. This study tested the potential effect of the ISAC in influencing dentists\' cognitive and behavioral skills, to enhance early detection and prevention of OC. A quasi-experimental study was conducted among dental interns (DIs) at dental setting to test the effect on comprehensive oral cancer examination score (COCE), awareness, self-efficacy, descriptive-norms, and self-reported behavior. Data were collected through triangulation of methods pre and post the intervention at two-months. Multiple linear mixed effects regression models were utilized for data analysis. Between October 2020 and April 2021, 47 DIs participated in the study. The final model showed the significant effects of time (ISAC) on COCE (95% CI = 25.12-29.42, P < .001). DIs had a significant improvement in awareness, self-efficacy, descriptive norms, and self-reported behavior. The findings showed promising effects of the intervention toward the early detection and prevention of OC. Dentists, dental organizations, and policymakers in areas with a high risk of OC could benefit from the current intervention which contributes to capacity building and improved community health. A pragmatic study with a robust design is needed to test the effectiveness of the intervention on a wider scale.

UNASSIGNED: In this study, we investigated the expression of zinc alpha-2 glycoprotein in oral squamous cell carcinoma tissue samples. Additionally, ascertained its association to the oral cancer stage and subscale parameters (TNM).
UNASSIGNED: This observational study was conducted at Ziauddin University from January to December 2020. Using the Open-Epi software, the sample size of 120 oral squamous cell carcinomas was calculated at 95% confidence interval and a 5% margin of error. Ethical approval was taken from the Institutional Ethical Review Committee. Histologically diagnosed cases of oral squamous cell carcinoma were obtained from the Histopathology Department of Ziauddin University, Karachi. Study data was analyzed through SPSS version-20 and p-value ≤0.05 considered as significant. One-way ANOVA and Multiple linear regression were applied for analysis of data.
UNASSIGNED: In the study, none of the oral squamous cell carcinoma tissue samples from the later stages were stained for ZAG. However 71% (35/49) of the early stage OSCC samples showed positive IHC results for ZAG expression in the cytoplasm. One-way ANOVA indicates that high ZAG expression was significantly associated with smaller tumor size (p<0.001), lymph node involvement (p=0.002), early stages of OSCC (p<0.001) and less differentiated tumor (p=0.001). The site of the tumor was also significantly associated with ZAG staining (p<0.001).
UNASSIGNED: Zinc alpha-2 glycoprotein expressed in the early stages of oral cancer development so that effective treatment modalities can be planned as per the patient\'s status. This may also assist a clinician to achieve tumor-free surgical margins and monitor the post treatment outcomes.

Oral squamous cell carcinoma (OSCC) is characterized by poor survival, mostly due to local invasion, loco-regional recurrence, and metastasis. Given that the weakening of cell-to-cell adhesion is a feature associated with the migration and invasion of cancer cells, different studies have explored the prognostic utility of cell adhesion molecules such as E-cadherin (E-cad). This study aims to summarize current evidence in a meta-analysis, focusing on the prognostic role of E-cad in OSCC. To find studies meeting inclusion criteria, Scopus, Web of Science, EMBASE, Medline, and OpenGrey databases were systematically assessed and screened. The selection process led to 25 studies, which were considered eligible for inclusion in the meta-analysis, representing a sample of 2553 patients. E-cad overexpression was strongly associated with longer overall survival (OS) with Hazard Ratio (HR)  = 0.41 95% confidence interval (95% CI) (0.32-0.54); p < 0.001 and disease-free survival with HR 0.47 95% CI (0.37-0.61); p < 0.001. In terms of OS, patients with tongue cancer experienced better survivability when expressing E-cad with HR 0.28 95% CI (0.19-0.43); p < 0.001. Globally, our findings indicate the prognostic role of the immunohistochemical assessment of E-cad in OSCC and its expression might acquire a different role based on the oral cavity subsites.

BACKGROUND: Oral cancer screening strategies help reduce associated mortality and could be performed by a trained frontline health worker (FHW). The present review aims to assess the diagnostic accuracy of commonly used screening modalities for oral cancer performed by FHW in apparently healthy individuals.
METHODS: Electronic databases PubMed, Scopus, Embase, Cochrane Library, and Google Scholar, were searched. The review included studies conducted where apparently healthy adult individuals were screened by the FHW for cancer or PMD of the lip and oral cavity by any of the four commonly used techniques - Conventional Oral Examination (COE), toluidine blue staining (TBS), Oral Cytology (OC), and Chemiluminescent Illumination (CLI).
RESULTS: A total of 2,413 potentially relevant articles were retrieved from the search, among which five studies for COE were included in the review. Four out of those five studies were done before the year 2000. None of the studies fitted the inclusion criteria for TBS, OC, and CLI. Pooled sensitivity of oral screening by COE performed by an FHW (n=5) was 88.8% (95% CI: 71.6-96.1), whereas pooled specificity was 91.9% (95% CI: 78.3-97.3). On subgroup analysis, the pooled sensitivity and specificity of studies where the prevalence of disease was <50% (n=4) was 84.5% (95% CI: 62.6 - 94.7) and 94.1% (95% CI: 82.2 - 98.2), respectively.
CONCLUSIONS: COE by trained FHW had high pooled sensitivity and specificity for screening of oral cancer and PMDs. The screening techniques TBS, OC, and CLI, were not studied for mass screening by trained FHW. COE by trained FHW could be utilized for oral screening in limited-resource settings. However, the FHW should be sufficiently trained to get the desired benefits of early detection.
BACKGROUND: Department of Health Research, Ministry of Health & Family Welfare, Government of India.

OBJECTIVE: Nicotine is an ingredient of tobacco, and exposure to nicotine increases the risks of various cancers, including oral cancer. Previous studies have focused on the addictive properties of nicotine, but its carcinogenic mechanism has rarely been studied. We aimed to explore the key genes in the process through which nicotine promotes the occurrence and development of oral cancer via data mining and experimental verification.
METHODS: This study involved three parts. First, key genes related to nicotine-related oral cancer were screened through data mining; second, the expression and clinical significance of a key gene in oral cancer tissues were verified by bioinformatics. Finally, the expression and clinical significance of the key gene in oral cancer were histologically investigated, and the effects of its expression on cell proliferation, invasion, and drug resistance were cytologically assessed.
RESULTS: SERPINE1 was identified as the key gene, which was upregulated in nicotine-treated oral cells and may be an independent prognostic factor for oral cancer. SERPINE1 was enriched in various pathways, such as the tumor necrosis factor and apelin pathways, and was related to the infiltration of macrophages, CD4+T cells, and CD8+T cells. Overexpression of SERPINE1 was associated with N staging and may be involved in hypoxia, angiogenesis, and metastasis. Knockdown of SERPINE1 in oral cancer cells resulted in weakened cell proliferation and invasion ability and increased sensitivity to bleomycin and docetaxel.
CONCLUSIONS: This study revealed SERPINE1 as a key gene for nicotine-related oral cancer, indicating that SERPINE1 may be a novel prognostic indicator and therapeutic target for oral carcinoma.

Human epidermal growth factor receptor 2/neu (HER2/neu) is known to serve as a prognostic and predictive biomarker in several cancers such as breast, gastric and ovarian cancers. In head and neck squamous cell carcinoma, HER2/neu expression is seen but in a fluctuated manner. Hence, its role as a prognostic factor in oral squamous cell carcinoma (OSCC) needs evaluation. To determine the HER 2/neu overexpression in OSCC patients and its association with clinical and pathological parameters. 74 patients of OSCC treated between 2016 and 2018 were included in the study. Immunohistochemistry was done on tissue samples from these patients and HER2/neu expression was measured. Both biopsy and resected specimens were considered for the study. Out of 74 patients, 47.3% (35) were operated and 52.7% (39) were not operated due to loss to follow-up. No significant association was found (p = 0.636, OR = 0.68, CI = 0.14-3.34) between lymphovascular invasion (LVI) and HER2/neu expression. Similar results were seen for perineural invasion (PNI) (p = 0.490, OR = 0.53, CI = 0.88-3.24), depth of invasion (p = 0.21), grade of tumor (p = 0.214), clinical-stage (p = 0.511) and pathological stage (p = 0.091). No significant association existed between HER2/neu expression and LVI, PNI, clinical-stage, the grade of tumor and the pathological stage of oral squamous cell carcinoma.