Introduction

Oral cancer is a serious global health issue and one of the top ten malignancies worldwide [ 1 ]. Almost 90% of this type of cancer originates from squamous cells, which is classified as oral squamous cell carcinoma (OSCC) [ 1 - 2 ]. The incidence of oral cancer is about two to three times higher among men than among women [ 3 ]. A considerable prevalence of the disease has been reported in Melanesia (Papua New Guinea) and in South-central Asia, including India, Pakistan, Sri Lanka, India, Nepal, and Bangladesh [ 4 - 5 ]. It is quite concerning that more and more young adults under the age of 30 are suffering from OSCC, according to a recent study [ 6 ]. Oral cancers are now considered a global concern due to their high incidence and low five-year survival rates. In spite of better surgical procedures and novel therapies, the survival and recurrence rates for head and neck SCC have fairly improved globally over the past few decades [ 7 ]. An increasing trend has been reported for oral cavity and pharynx cancers in the United States, about 1% per year. On average, the mortality rate of cancers of the oral cavity and pharynx has increased by 0.4% every year. For men and women, human papillomavirus (HPV)-related oral cancers increased by about 2.8% and 1.3% per year, respectively, while smoking-related oral cancers decreased by about 0.8% per year [ 8 - 9 ]. In spite of the fact that the 5-year survival rate for OSCC is around 40%, the rate could be increased up to 80% if it is detected in the early stages [ 10 ]. According to worldwide data in 2020, the number of new cases and the mortality rate for lip and oral cavity cancer were 377,713 and 177,757, respectively [ 2 , 5 ].

Oral cancer is a malignant neoplasia that can manifest itself anywhere in the oral cavity, lips, sinuses, or pharynx. The most common sites for the presentation of oral cancer are the floor of the mouth, lower lip, and lateral border of the tongue [ 11 - 12 ]. It has been reported that OSCC frequently arises from a pre-existing oral lesion called precursor lesions [ 13 ]. Oral precancerous lesions, such as leukoplakia and erythroplakia as the most prevalent ones, are morphologically changed tissues with malignant transformation potential [ 14 - 15 ]. The clinical appearance of oral cancer varies greatly, and the presentation in oral cavity is linked to the primary tumor. Oral cancer most frequently presents itself as an ulcerated lesion in the oral cavity, pain, or numbness in the mouth or face, or an ill-fitted denture [ 16 ]. Dry mouth, mucositis, and dysphagia are the most conspicuous symptoms of oral cancer, which appear during and after cancer treatment [ 17 ]. Hyposalivation is the most commonly known symptom in oral cancer, where a reduction in salivary gland flow causes fungal infection, altered taste, and swallowing problems [ 18 - 19 ].

The need to preserve both functional and aesthetic aspects make the management of oral cancer difficult as related to life quality, throughout the tumor resection and other treatment modalities. In addition, the tumor and its treatment can affect a variety of functions, including sight, hearing, speaking, respiration, taste, jaw movement, and mastication. Additionally, it is important to note that oral cancer is frequently detected in an advanced stage, making early diagnosis essential [ 20 ]. Therefore, screening oral cancer for early detection and finding the best biomarkers for diagnosis is a crucial concern.

Search Strategy

Initially, a search was conducted using the keywords “Oral Squamous Cell Carcinoma” and each of the related terms including “etiology, risk factors, treatment, diagnosis, and screening” in the title/abstract of the published findings. Then the search was narrowed down using the keyword combination “Oral Squamous Cell Carcinoma AND tumor biomarkers AND screening” to get the most relevant studies. The search was mainly through the PubMed/Google scholar/Scopus databases. For early screening, articles published in English up to 2023 were recommended. The abstracts were evaluated and the irrelevant, outdated findings and non-English studies were excluded. To make the search as comprehensive as possible, the authors incorporated all types of studies related to the subtopics. To provide additional information for the review articles, the original articles used as references were also investigated. Following the assessment of the abstracts, the full text of the selected articles was reviewed, if they met the inclusion and exclusion criteria.

Results

As a result, 105 articles were chosen out of 132 for writing the main manuscript. There were 27 articles excluded, of which 4 articles were not written in English, 16 articles were irrelevant, and 7 articles were outdated. The remaining articles contained all required findings, especially tumor biomarkers used to screen for OSCC. A statistical analysis was not possible due to the variety of methods, populations, and study designs.

Literature Review

This literature review intends to discuss the etiology, risk factors, screening strategies, and treatment options for OSCC, focusing on the tumor biomarkers available for early diagnosis.

Etiology and risk factors for OSCC

Cigarette smoking habit and high alcohol intake are two major contributors to oral cancer. Snuff smoke is carcinogenic, and it can cause oral cavity and pancreatic cancer. Compared with non-smokers, smokers have a three times higher risk of developing oral cancer [ 21 ]. A smoky environment is also risky. There is an 87% greater risk of oral cancer among never-smokers who have been exposed to cigarette smoke than those never-smokers who have not been exposed [ 22 ]. The carcinogenic substances within cigarettes damage DNA, interfere with DNA repair mechanisms, and weaken the immune components in the oral cavity, which may lead to tumorigenesis [ 23 - 24 ]. For instance, cigarette smoking could promote OSCC development by activating receptor-interacting protein 2 / nuclear factor κB (RIP2/NF-κB) signaling pathway and upregulating caspase-12 as a result, a factor which is involved in weakening the mucosal immunity [ 25 ]. The activation of Wnt/ mitogen-activated protein kinases (MAPK) pathways and an increase in reactive oxygen species (ROS) levels afterwards may be the cause of cancerous alterations in the epithelial cells following cigarette smoking [ 26 ]. ROS could damage DNA, therefore, evaluating the levels of DNA damage-associated proteins such as H2A histone family member X (H2AX), checkpoint kinase 2 (CHK2), and P53 in smokers might be used to estimate the risk of developing cancer [ 27 - 28 ]. Nevertheless, recent studies using the IHC method revealed a similar immunoexpression of these proteins in OSCC samples of smokers and non-smokers [ 29 ]. As a result of smoking, mucin1 (MUC1) may be overexpressed in the oral epithelial cells and localized from the superficial to basal cell layer of the oral epithelium, leading to an increased risk of developing oral epithelial dysplasia (OED) and OSCC afterwards [ 30 ]. Several events have been associated with cigarette smoke condensate (CSC)-induced tumor progression in a recent study, including miR-30a downregulation and overexpression of binding immunoglobulin protein (BiP) as an endoplasmic reticulum (ER) stress regulator that enhances vascular endothelial growth factor (VEGF) production and secretion in OSCC cells both in vivo and in vitro [ 31 ].

Alcohol is another important risk factor for oral cancer [ 32 - 33 ]. Alcohol leads to the dissolving of lipids components of the epithelium, causing epithelial atrophy and interference in DNA synthesis and DNA repair mechanisms, and increased permeability of oral mucosa. It contains genotoxic and mutagenic effects, resulting in a reduction in salivary flow. Chronic alcohol intake is linked to a disturbance in innate and acquired immunity, rendering more susceptibility to infections and cancers [ 32 - 33 ]. Recent findings revealed a possible association between heavy alcohol consumption, Toll-like receptor (TLR-9 high) tumors with reduced intratumoral CD8⁺ cells, and lower survival rates in OSCC patients [ 34 ]. Following prolonged alcohol consumption, nuclear factor of activated T cells (NFAT) signaling may be activated, increasing cancer stemness and aerobic glycolysis [ 35 ]. Other cancer-predisposing factors, including chronic irritation, exposure to other carcinogens, poor oral hygiene, viral infections including HPV, malnutrition, and genetic factors, are also suggested [ 36 ]. Genetic variation in proto-oncogenes (Myc), tumor suppressor genes (APC, p53), genes controlling normal cellular processes (EIF3E, GSTM1), and oncogene (Ras) have been suggested to play a role in the etiology of oral cancer. Other contributing factors include DNA damage repair, segregation of chromosomes, loss of heterozygosity, telomere stabilities, defects in notch signaling pathways, and regulations of cell-cycle checkpoints [ 36 - 39 ]. Lower serum vitamin D levels have been associated with an increased risk of OSCC, a lower chance of survival, and more negative chemotherapy side effects in these patients, according to a recent systematic analysis [ 40 ].

Treatment strategies for OSCC

Treatment of oral cancers needs a delicate and careful approach to preserve adjacent tissues and organs, which is crucial to the patient’s quality of life. Generally, oral cancer can be cured, especially in those with smaller tumors and early stages, coupled with this, a reverse correlation between tumor size and the survival rate has been reported [ 41 ]. Treatment of oral cancers comprises four different modalities: surgery, radiation therapy, chemotherapy, and immunotherapy (including the use of monoclonal antibodies and immune checkpoint inhibitors) [ 42 ]. Depending on the stage and extension of the tumor, possible side effects, and the patient's overall health, one or a mixture of these will be applied. However, surgery is the first option in most cases, a well-accepted treatment for most oral cancers. Following tumor resection, the rehabilitation and reconstruction of affected surrounding tissues are essential to maintain the aesthetics and quality of life. Surgery is the tumor’s excision with some healthy surrounding tissue, called a safe margin (SM). The extension of the SM varies, depending on the anatomic location and tumor invasion. The most common surgical procedures implemented in oral cancer include glossectomy, mandibulectomy, maxillectomy, and neck dissection [ 43 - 44 ].

Screening for OSCC

Early diagnosis is a critical element in reducing the mortality rate of oral cancers. According to the tumor node and metastasis (TNM) classification, tumor size plays a crucial role in the mortality and morbidity rate. Unfortunately, in most countries, many patients with oral cancer are diagnosed with advanced disease (stages III/IV) with multiple metastases. As a result, the five-year survival rate for stage I oral cancer is over 80%, compared with roughly 20% for advanced stages. Consequently, oral screening is regarded as the best strategy to reduce patients’ mortality and morbidity rates, especially among high-risk individuals [ 45 - 46 ]. In the case of oral cancer, screening deals with symptomatic patients with none-healing suspicious lesions, a normal population identifying early changes in oral epithelium and oral abnormality associated with dysplastic features [ 47 ]. Different screening strategies for OSCC have been illustrated in Figure 1.

Figure 1. Steps in oral squamous cell carcinoma (OSCC) screening, from a routine visual examination to a sophisticated molecular detection

Diagnostic value of biopsy for OSCC

For many years, routine oral examination has been the primary means of detecting and diagnosing oral malignancies. Biopsy and histopathological analysis, as the gold standards for OSCC diagnosis, will further be prescribed for suspicious findings in clinical examinations. Although histopathology provides a definitive diagnosis for oral cancers, it is a sensitive technique that requires several days of processing for clinicians to obtain results. Based on the pathological findings, severe dysplasia extending beyond the epithelium and invasion of the underlying lamina propria is regarded as carcinoma. Although dysplasia in histopathology is regarded as an elevated risk of malignant transformation, it is a snapshot of the current situation, which will not predict future malignant transformation [ 48 ]. Based on this, premalignant lesions and those confirmed with dysplastic changes must be observed clinically and require multiple biopsies to detect any changes over time.

A perfect specimen must have sufficient size that includes both the suspected lesion and normal surrounding tissue. A biopsy sample must include tissues with the greatest dysplastic signs and represent the significant changes in epithelium. As a case in point, those areas with a sign of induration, ulcer, and reddish demonstration are the potential sites to collect the biopsy. Other factors should be considered to improve histopathological diagnosis, including access to vital clinical information and surgical findings for the pathologist [ 49 ]. Finally, a knowledgeable and expert oral pathologist plays a mandatory role in the biopsy’s outcome. Overall, histopathology observes changes at the cellular level, while further detection of molecular changes requires extra specific tools.

Visual examination

Among several screening methods, visual examination is a fundamental method to discover clinical changes in oral epithelium, including ulceration, tooth mobility, and changes in the surface texture. Reports indicated that visual examination is the most readily available method to detect precancerous lesions, especially in individuals at high risk of oral cancers, together with heavy drinkers and smokers [ 50 ].

Although the visual examination is a cheap and accessible oral examination method, it does not provide strong sensitivity and specificity for diagnosing oral lesions. Therefore, other complementary methods have been introduced to help clinicians detect early changes and define the lesions' nature [ 51 - 52 ]. Currently available techniques are Toluidine blue staining, micro-brush cytology, biomarkers, and optical techniques [ 46 ]. Below, some of the most common methods will be covered.

Vital staining

Implementation of toluidine blue (TB) staining before a biopsy is a valuable and inexpensive way to highlight suspected malignant areas. Malignant cells have elevated nuclear activity with higher DNA content. TB binds to abnormal cells' nucleus component with higher intensity because of their high affinity for nucleic acid [ 53 ]. Therefore, it is considered a non-invasive method that highlights the lesion, assisting the clinicians in collecting an accurate biopsy [ 54 ]. It has been reported that TB as a simple and accessible method is recommended to screen the high-risk population, detecting malignant and premalignant lesions more potent than the conventional oral examination (96.7% and 40% sensitivity, respectively). The presence of blue dye with no further confirmation of carcinoma (false positive) occurs in 8-10% of cases, while the false-negative result is usually rare [ 55 ]. One of the advantages of the vital staining screening methodology is that this method requires no dentist/ specialist and it can be performed at the primary dental care level by any experienced oral healthcare provider.

Optical systems

In the past few years, new technology was introduced in which suspicious tissues are exposed to an external light source, exciting certain amino acids, metabolic products, and structural proteins inside the tissue, creating visible and quantifiable light. Needless to say, in oral epithelium abnormalities, the emission rate is interpreted as changes in cellular morphology. Changes in the intensity of color by an exogenous source distinguish normal from abnormal tissues [ 56 - 57 ]. One of the recently introduced optical systems is fluorescent visualization, a non-invasive and repeatable method. In this system, the normal and the precancerous mucosa are visualized differently [ 58 ]. The high false-positive result rate is reported to be one of the disadvantages of optical systems [ 59 ]. There have also been arguments made in the literature about the utility of optical systems, detecting oral lesions superior to the oral examination. A more comprehensive cohort study is required to validate these assertions.

Oral brush biopsy

Cytology brush was first introduced in 1963, but it was not accepted among clinicians because of its low sensitivity and specificity to detect dysplastic and malignant lesions [ 60 ]. Advancements in this technology have provided an excellent opportunity to employ this approach as a conventional screening program. Implementation of the cytology brush in oral lesion detection was followed by its successful application in cervical cancer [ 61 ]. Patients are more receptive to this approach, because the oral cytology brush (OCB) is a safe and minimally invasive procedure to collect oral mucosa cells. Therefore, it is regarded as a promising approach for screening and early diagnosis of oral premalignant lesions [ 60 ].

Several reasons have been reported for poor sensitivity and false negative results from OCB. To exemplify, obtaining samples from a superficial rather than a full-thickness layer, the presence of blood/debris, and other obscuring factors were mentioned [ 60 , 62 - 63 ]. Combining liquid base cytology (LBC) with conventional OCB has provided greater diagnostic accuracy to detect abnormal tissues [ 64 ]. In this method, mucosal cells are harvested by a plastic device and then kept in a preservative medium until transferred to the laboratory [ 65 ]. Although several studies supported using oral cytology combined with LBC, a longitudinal cohort study with a large sample size must be conducted to validate the efficacy and accuracy of this method [ 64 , 66 ].

Tumor biomarkers

The development of immunological techniques has led scientists to look for changes at the cellular and molecular levels in cancers. Detection of abnormal gene/protein expression in biological specimens has opened various windows to the world of tumor biomarkers for cancer screening. As an instance, prostate-specific antigen (PS-A) for prostate cancer, cancer antigen 125 (CA-125) for ovarian cancer, and carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9) for gastrointestinal cancers have long been used in cancer screening [ 67 ].

Biomarkers are generally categorized at the level of metabolomics, proteomics, and genomics. Oral cancer molecular biology and oncology research focus on key biological markers or molecules that can contribute to risk assessment, cancer formation, recurrence prediction, screening, invasion/metastasis, prognosis, and monitoring cancer therapy response [ 68 ].

Salivary/Serum (Plasma)/ Tissue biomarkers

Saliva has been indicated as an alternative medium for screening oral cancer since it is non-invasive, inexpensive, and easily accessible to collect [ 69 ]. Saliva contains several chemokine/cytokine and exfoliated cells, which allows not only for genetic changes to be assessed but is also a powerful search tool for protein biomarkers in individuals with a high risk of developing oral cancer [ 62 ]. In recent years, saliva has been subjected to proteomics technology to find new biomarkers for oral cancers [ 70 ]. It appears that salivary biomarkers such as mRNA and miRNA estimated through the polymerase chain reaction (PCR) have a good screening potential for early detection of OSCC, but further research will be required in order to confirm these findings [ 71 ]. According to a recent systematic and meta-analysis review, salivary mRNA biomarkers including dual specificity 1 protein (DUSP-1) and calcium-binding protein S100P demonstrated the highest specificity and sensitivity for early detection of OSCC (91%) [ 72 ]. Recent advancements in the identification of salivary biomarkers for OSCC using transcriptomic, proteomic, and metabolomics strategies have been mentioned in Tables 1-3 respectively. Using gas chromatography mass spectrometry (GC/MS) for metabolomics analysis, it was discovered that glucose, cysteine+cysteine, nonanoicic acid, and galactose might all be used as possible biomarkers for OSCC screening [ 73 ].

Tables 4 and 5 provide an overview of recent advancements in identifying serum (plasma) and tissue biomarkers for OSCC. Additionally, biomarkers can be utilized to identify therapeutic targets and monitor the effectiveness of treatment. In this regard, Monteiro et al. [ 74 ] have demonstrated that the overexpression of a mammalian target of rapamycin (mTOR) protein can be considered a potential therapeutic target in individuals diagnosed with OSCC. Yang et al. [ 75 ] have also shown that growth differentiation factor 15 (GDF15) expression might be implemented as a prognostic and predictive marker for patients undergoing induction treatment with cisplatin, docetaxel, and 5fluorouracil (TPF). Some biomarkers detect germline mutations that are effective in predicting individuals at high risk of cancer development. These biomarkers are involved in the cell cycle, apoptosis, and cancer risks, such as polymorphism in p53/p73, murine double minute 2 (MDM2), cyclin D1 (CCND1), and heavy Ras (H-Ras) [ 76 ]. Another implication of biomarkers in oral cancer is to detect probable recurrence in patients who have had adjuvant treatment.

Sulzyc-Bielicka et al. [ 77 ] showed that patients with increased thymidylate synthase (TS) expression are at a higher risk of early recurrence of oral cancer in the post-treatment interval. Regarding the use of biomarkers to detect invasion, metastasis, and monitor therapeutic response in patients with metastatic carcinoma, Huang et al. [ 78 ] identified miRNA-459-5p and G-protein-coupled receptor kinase-interacting protein 1 (GIT1) as potential biomarkers for the invasion and metastatic phenotypes in OSCC, and their expression levels are inversely correlated.

Conclusion

Oral cancer is a major public health concern, currently ranked among the top ten global challenges. Therefore, the availability of powerful screening tools for early detection is a core question. The biomarkers could target different parts of the body, especially the saliva and the oral cavity. Considering the value of biomarkers for early diagnosis, prognosis, and recurrent potential in post-treatment, the development, and discovery of new biomarkers is still a work in progress. It is expected that advancements in new high-throughput technologies such as proteomics and collection and evaluation of the big RNA-seq data introduction of new and reliable bio-markers for OSCC will become a reality in the not-too-distant future.

Acknowledgment

This research did not receive any specific grant from funding agencies in the public, commercial, or notforpro fit sectors.

Conflicts of Interest:

The authors declare that they have no conflict of interest.

References

1. Rivera C. Essentials of oral cancer. Int J Clin Ex Patho. 2015; 8: 11884.
2. Kim YJ, Kim JH. Increasing incidence and improving survival of oral tongue squamous cell carcinoma. Sci Rep. 2020; 10: 1-11.
3. Di Spirito F, Amato A, Romano A, Dipalma G, Xhajanka E, Baroni A, et al. Analysis of risk factors of oral cancer and periodontitis from a sex-and gender-related perspective: gender dentistry. Appl Sci. 2022; 12: 9135.
4. Sarode G, Maniyar N, Sarode SC, Jafer M, Patil S, Awan Kh. Epidemiologic aspects of oral cancer. Dis Mon. 2020; 66: 100988.
5. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Can J Clin. 2021; 71: 209-249.
6. Alramadhan SA, Fitzpatrick SG, Cohen DM, Bhattacharyya I, Islam MN. Incidence of oral squamous cell carcinoma in patients aged 30 years and under: a single institution retrospective analysis. Saudi J Oral Dent Res. 2022; 7: 351-358.
7. Capote-Moreno A, Brabyn P, Muñoz-Guerra M, Sastre-Pérez J, Escorial-Hernandez V, Rodríguez-Campo F, et al. Oral squamous cell carcinoma: epidemiological study and risk factor assessment based on a 39-year series. Int J Oral Maxillofac Surg. 2020; 49: 1525-1534.
8. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA A Can J Clin. 2022; 72: 7-33.
9. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA A Can J Clin. 2023; 73: 17-48.
10. Abati S, Bramati C, Bondi S, Lissoni A, Trimarchi M. Oral cancer and precancer: a narrative review on the relevance of early diagnosis. Int J Environ Res Public Health. 2020; 17: 9160.
11. Dhanuthai K, Rojanawatsirivej S, Thosaporn W, Kintarak S, Subarnbhesaj A, Darling M, et al. Oral cancer: A multicenter study. Med Oral Oral Cir Bucal. 2018; 23: e23.
12. Howard A, Agrawal N, Gooi Z. Lip and Oral Cavity Squamous Cell Carcinoma. Hematol Oncol Clin. 2021; 35: 895-911.
13. McCord C, Kiss A, Magalhaes MA, Leong IT, Jorden T, Bradley G. Oral Squamous Cell Carcinoma Associated with Precursor LesionsOral Cancer Associated with Precursor Lesions. Cancer Prev Res. 2021; 14: 873-884.
14. Phookan J, Saikia K. A clinicopathological study of the pre-malignant conditions of oral cavity. Indian J Otolaryngol Head Neck Surg. 1998; 50: 246-249.
15. Yardimci G, Kutlubay Z, Engin B, Tuzun Y. Precancerous lesions of oral mucosa. World J Clin Case (WJCC).. 2014; 2: 866.
16. Wong T, Wiesenfeld D. Oral Cancer. Australian Dent J. 2018; 63: S91-S9.
17. Mercadante S, Aielli F, Adile C, Ferrera P, Valle A, Fusco F, et al. Prevalence of oral mucositis, dry mouth, and dysphagia in advanced cancer patients. Support Care Cancer. 2015; 23: 3249-3255.
18. Hanchanale S, Adkinson L, Daniel S, Fleming M, Oxberry SG. Systematic literature review: xerostomia in advanced cancer patients. Support Care Cancer. 2015; 23: 881-888.
19. Plemons JM, Al-Hashimi I, Marek CL. Managing xerostomia and salivary gland hypofunction: executive summary of a report from the American Dental Association Council on Scientific Affairs. J Am Dent Assoc. 2014; 145: 867-873.
20. Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nat Rew Dis Primers. 2020; 6: 1-22.
21. Edirisinghe ST, Weerasekera M, De Silva DK, Liyanage I, Niluka M, Madushika K, et al. The risk of oral cancer among different categories of exposure to tobacco smoking in Sri Lanka. Asian Pac J Cancer Prev. 2022; 23: 2929-2935.
22. Lee YCA, Marron M, Benhamou S, Bouchardy C, Ahrens W, Pohlabeln H, et al. Active and involuntary tobacco smoking and upper aerodigestive tract cancer risks in a multicenter case-control study. Cancer Epidemiol Biomarkers Prev. 2009; 18: 3353-3561.
23. Hussain A, Dulay P, Rivera MN, Aramouni C, Saxena V. Neoplastic pathogenesis associated with cigarette carcinogens. Cureus. 2019; 11: e3955.
24. Lee J, Taneja V, Vassallo R. Cigarette smoking and inflammation: cellular and molecular mechanisms. J Dent Res. 2012; 91: 142-149.
25. Qian Y, Wang W, Chen D, Zhu Y, Wang Y, Wang X. Cigarette smoking induces the activation of RIP2/ caspase-12/NF-κB axis in oral squamous cell carcinoma. Peer J. 2022; 10: e14330.
26. Sarkar R, Das A, Paul RR, Barui A. Cigarette smoking promotes cancer-related transformation of oral epithelial cells through activation of Wnt and MAPK pathway. Future Oncology. 2019; 15: 3619-3631.
27. De Oliveira SRL, Da Silva ICB, Mariz BALA, Pereira AMBC, De Oliveira NFP. DNA methylation analysis of cancer-related genes in oral epithelial cells of healthy smokers. Arch Oral Biol. 2015; 60: 825-833.
28. Valinluck V, Sowers LC. Inflammation-mediated cytosine damage: a mechanistic link between inflammation and the epigenetic alterations in human cancers. Cancer Res. 2007; 67: 5583-5586.
29. Schuch LF, De Arruda JAA, Viana KSS, Caldeira PC, Abreu MHNG, Bernardes VF, et al. DNA damage-related proteins in smokers and non-smokers with oral cancer. Brazilian Oral Res. 2022; 36: e027.
30. Kashyap B, Mikkonen JJW, Bhardwaj T, Dekker H, Schulten EAJM, Bloemena E, et al. Effect of smoking on MUC1 expression in oral epithelial dysplasia, oral cancer, and irradiated oral epithelium. Arch Oral Biol. 2022; 142: 105525.
31. Chien CY, Chen YC, Lee CH, Wu JR, Huang TW, Huang RY, et al. Dysregulation of the miR-30a/BiP axis by cigarette smoking accelerates oral cancer progression. Cancer Cell Int. 2021; 21: 1-14.
32. Liu Y, Chen H, Sun Z, Chen X. Molecular mechanisms of ethanol-associated oro-esophageal squamous cell carcinoma. Cancer Lett. 2015; 361: 164-173.
33. Reidy J, McHugh E, Stassen L. A review of the relations hip between alcohol and oral cancer. The Surgeon. 2011; 9: 278-283.
34. Bolesina NJ, Gatti G, López de Blanc S, Dhooge S, Rocha D, Fernández E, et al. Oral Squamous Cell Carcinoma (OSCC) tumors from heavy alcohol consumers are associated with higher levels of TLR9 and a particular immunophenotype: impact on patient overall survival. Front Immunol. 2022; 13: 941667.
35. Nguyen A, Kim AH, Kang MK, Park NH, Kim RH, Kim Y, et al. Chronic alcohol exposure promotes cancer stemness and glycolysis in oral/oropharyngeal squamous cell carcinoma cell lines by activating NFAT signaling. Int J Mol Sci. 2022; 23: 9779.
36. Chamoli A, Gosavi AS, Shirwadkar UP, Wangdale KV, Behera SK, Kurrey NK, et al. Overview of oral cavity squamous cell carcinoma: Risk factors, mechanisms, and diagnostics. Oral Oncol. 2021; 121: 105451.
37. Ali J, Sabiha B, Jan HU, Haider SA, Khan AA, Ali SS. Genetic etiology of oral cancer. Oral Oncol. 2017; 70: 23-28.
38. Nigam K, Srivastav RK. Notch signaling in oral pre-cancer and oral cancer. Med Oncol. 2021; 38: 1-13.
39. Wu F, Shi X, Zhang R, Tian Y, Wang X, Wei C, et al. Regulation of proliferation and cell cycle by protein regulator of cytokinesis 1 in oral squamous cell carcinoma. Cell Death Dis. 2018; 9: 1-12.
40. Maturana-Ramírez A, Aitken-Saavedra J, de Guevara-Benítez AL, Espinoza-Santander I. Hypovitaminosis D, oral potentially malignant disorders, and oral squamous cell carcinoma: a systematic review. Med Oral Patol Oral Cir Bucal. 2022; 27: e135.
41. Van der Waal I. Are we able to reduce the mortality and morbidity of oral cancer; some considerations. Med Oral Patol Oral Cir Bucal. 2013; 18: e33.
42. Colevas AD, Yom SS, Pfister DG, Spencer S, Adelstein D, Adkins D, et al. NCCN guidelines insights: head and neck cancers, version version 1.2018. J Natl Compr Canc Netw. 2018; 16: 479-490.
43. Shah JP, Gil Z. Current concepts in management of oral cancer–surgery. Oral Oncol. 2009; 45: 394-401.
44. Hartner L. Chemotherapy for oral cancer. Dent Clin North Am. 2018; 62: 87-97.
45. D’Cruz AK, Vaish R. Risk-based oral cancer screening-lessons to be learnt. Nat Rev Clin Oncol. 2021; 18: 471- 472.
46. Wang S, Yang M, Li R, Bai J. Current advances in non invasive methods for the diagnosis of oral squamous cell carcinoma: a review. Eur J Med Res. 2023; 28: 1-12.
47. Jitender S, Sarika G, Varada HR, Omprakash Y, Mohsin K. Screening for oral cancer. J Exp Ther Oncol. 2016; 11: 303-307.
48. Badvi J, Kulsoom J, Ujjan I. Recent techniques for diagnosis of oral squamous cell carcinoma. EC Microbiol. 2017; 5: 165-168.
49. Rao RS, Chatura KR, Sowmya S, Prasad K, Lakshminarayana S, Ali FM, et al. Procedures and pitfalls in incisional biopsies of oral squamous cell carcinoma with respect to histopathological diagnosis. Dis Mon. 2020; 66: 101035.
50. Sciubba JJ. Oral cancer and its detection: history-taking and the diagnostic phase of management. J Am Dent Assoc. 2001; 132: 12S-18S.
51. Carreras-Torras C, Gay-Escoda C. Techniques for early diagnosis of oral squamous cell carcinoma: Systematic review. Med Oral Patol Oral Cir Bucal. 2015; 20: e305.
52. Epstein JB, Güneri P, Boyacioglu H, Abt E. The limitations of the clinical oral examination in detecting dysplastic oral lesions and oral squamous cell carcinoma. J Am Dent Assoc. 2012; 143: 1332-1342.
53. Epstein JB, Oakley C, Millner A, Emerton S, Van Der Meij E, Le N. The utility of toluidine blue application as a diagnostic aid in patients previously treated for upper oropharyngeal carcinoma. Oral Surg Oral Med Oral Patho Oral Radio Endo. 1997; 83: 537-547.
54. Parakh MK, Reddy RJ, Subramani P. Toluidine blue staining in identification of a biopsy site in potentially malignant lesions: A case–control study. Asia Pac J Oncol Nurs. 2017; 4: 356-360.
55. Epstein JB, Feldman R, Dolor RJ, Porter SR. The utility of tolonium chloride rinse in the diagnosis of recurrent or second primary cancers in patients with prior upper aerodigestive tract cancer. Head Neck. 2003; 25: 911-921.
56. Pavlova I, Williams M, El-Naggar A, Richards-Kortum R, Gillenwater A. Understanding the biological basis of autofluorescence imaging for oral cancer detection: high-resolution fluorescence microscopy in viable tissue. Clin Can Res. 2008; 14: 2396-2404.
57. Rashid A, Warnakulasuriya S. The use of light‐based (optical) detection systems as adjuncts in the detection of oral cancer and oral potentially malignant disorders: a systematic review. J Oral Patho Med. 2015; 44: 307-328.
58. Morikawa T, Shibahara T, Nomura T, Katakura A, Takano M. Non-invasive early detection of oral cancers using fluorescence visualization with optical instruments. Cancers. 2020; 12: 2771.
59. Bhatia N, Lalla Y, Vu AN, Farah CS. Advances in optical adjunctive AIDS for visualisation and detection of oral malignant and potentially malignant lesions. Int J Dent. 2013; 2013: 194029.
60. Mehrotra R, Gupta A, Singh M, Ibrahim R. Application of cytology and molecular biology in diagnosing premalignant or malignant oral lesions. Mol Cancer. 2006; 6: 1-9.
61. Smith JH. Cytology, liquid-based cytology and automation. Best Pract Res Clin Obstet Gynaecol. 2011; 25: 585-596.
62. Rosin MP, Epstein JB, Berean K, Durham S, Hay J, Cheng X, et al. The use of exfoliative cell samples to map clonal genetic alterations in the oral epithelium of high-risk patients. Can Res. 1997; 57: 5258-5260.
63. Kujan O, Desai M, Sargent A, Bailey A, Turner A, Sloan P. Potential applications of oral brush cytology with liquid-based technology: results from a cohort of normal oral mucosa. Oral Oncol. 2006; 42: 810-818.
64. Remmerbach T, Pomjanski N, Bauer U, Neumann H. Liquid-based versus conventional cytology of oral brush biopsies: a split-sample pilot study. Clin Oral Invest. 2017; 21: 2493-2498.
65. Hayama FH, Motta A, Migliari D. Liquid-based preparations versus conventional cytology: specimen adequacy and diagnostic agreement in oral lesions. Med Oral Patol Oral Cir Bucal. 2005; 10: 115-122.
66. Navone R, Burlo P, Pich A, Pentenero M, Broccoletti R, Marsico A, et al. The impact of liquid‐based oral cytology on the diagnosis of oral squamous dysplasia and carcinoma. Cytopathology. 2007; 18: 356-360.
67. Sarhadi VK, Armengol G. Molecular Biomarkers in Cancer. Biomolecules. 2022; 12: 1021.
68. Santosh ABR, Jones T, Harvey J. A review on oral cancer biomarkers: Understanding the past and learning from the present. J Can Res Ther. 2016; 12: 486.
69. Nguyen TTH, SodnomIsh B, Choi SW, Jung HI, Cho J, Hwang I, et al. Salivary biomarkers in oral squamous cell carcinoma. J Korean Assoc Oral Maxillofac Surg. 2020; 46: 301-312.
70. Riccardi G, Bellizzi MG, Fatuzzo I, Zoccali F, Cavalcanti L, Greco A, et al. Salivary biomarkers in oral squamous cell carcinoma: a proteomic overview. Proteomes. 2022; 10: 37.
71. Shaw AK, Garcha V, Shetty V, Vinay V, Bhor K, Ambildhok K, et al. Diagnostic accuracy of salivary biomarkers in detecting early oral squamous cell carcinoma: a systematic review and meta-analysis. Asian Pac J Cancer Prev. 2022; 23: 1483-1495.
72. Gaba FI, Sheth CC, Veses V. Salivary biomarkers and their efficacies as diagnostic tools for oral squamous cell carcinoma: systematic review and meta‐analysis. J Oral Patho Med. 2021; 50: 299-307.
73. Enomoto Y, Kimoto A, Suzuki H, Nishiumi S, Yoshida M, Komori T. Exploring a novel screening method for patients with oral squamous cell carcinoma: A plasma metabolomics analysis. Kobe J Med Sci. 2018; 64: E26.
74. Monteiro LS, Delgado ML, Ricardo S, Garcez F, do Amaral B, Warnakulasuriya S, et al. Phosphorylated mammalian target of rapamycin is associated with an adverse outcome in oral squamous cell carcinoma. Oral Surg Oral Med Oral Patho Oral Radio. 2013; 115: 638-645.
75. Yang C, Ma J, Zhu D, Liu Y, Montgomery B, Wang L, et al. GDF15 is a potential predictive biomarker for TPF induction chemotherapy and promotes tumorigenesis and progression in oral squamous cell carcinoma. Ann Oncol. 2014; 25: 1215-1222.
76. Bag A, Jyala N, Bag N. Indian studies on genetic polymorphisms and cancer risk. Indian J Can. 2012; 49: 144.
77. Sulzyc-Bielicka V, Bielicki D, Binczak-Kuleta A, Kaczmarczyk M, Pioch W, Machoy-Mokrzynska A, et al. Thymidylate synthase gene polymorphism and survival of colorectal cancer patients receiving adjuvant 5-fluorouracil. Genet Test Mol Biomarkers. 2013; 17: 799-806.
78. Huang WC, Chan SH, Jang TH, Chang JW, Ko YC, Yen TC, et al. miRNA-491-5p and GIT1 serve as modulators and biomarkers for oral squamous cell arcinoma invasion and metastasis. Can Res. 2014; 74: 751-764.
79. Scholtz B, Horváth J, Tar I, Kiss C, Márton IJ. Salivary miR-31-5p, miR-345-3p, and miR-424-3p are reliable biomarkers in patients with oral squamous cell carcinoma. Pathogens. 2022; 11: 229.
80. Cai M, Zheng Z, Bai Z, Ouyang K, Wu Q, Xu S, et al. Overexpression of angiogenic factors and matrix metalloproteinases in the saliva of oral squamous cell carcinoma patients: Potential non-invasive diagnostic and therapeutic biomarkers. BMC Cancer. 2022; 22: 1-15.
81. Rapado‐González Ó, López‐Cedrún JL, Lago‐Lestón RM, Abalo A, Rubin‐Roger G, Salgado‐Barreira Á, et al. Integrity and quantity of salivary cell‐free DNA as a potential molecular biomarker in oral cancer: A preliminary study. J Oral Patho Med. 2022; 51: 429-435.
82. Ueda S, Goto M, Hashimoto K, Hasegawa S, Imazawa M, Takahashi M, et al. Salivary CCL20 level as a biomarker for oral squamous cell carcinoma. Cancer Genomics Proteomics. 2021; 18: 103-112.
83. Koopaie M, Manifar S, Lahiji SS. Assessment of micro-RNA-15a and microRNA-16-1 salivary level in oral squamous cell carcinoma patients. Microrna. 2021; 10: 74-79.
84. Ueda S, Goto M, Hashimoto K, Imazawa M, Takahashi M, OhIwa I, et al. Salivary CPLANE1 levels as a biomarker of oral squamous cell carcinoma. Anticancer Res. 2021; 41: 765-772.
85. Romani C, Salviato E, Paderno A, Zanotti L, Ravaggi A, Deganello A, et al. Genome-wide study of salivary miRNAs identifies miR-423-5p as promising diagnostic and prognostic biomarker in oral squamous cell carcinoma. Theranostics. 2021; 11: 2987.
86. Mehterov N, Vladimirov B, Sacconi A, Pulito C, Rucinski M, Blandino G, et al. Salivary miR-30c-5p as potential biomarker for detection of oral squamous cell carcinoma. Biomedicines. 2021; 9: 1079.
87. Farag AF, Sabry D, Hassabou NF, Alaa EL-Din Y. MicroRNA-134/microRNA-200a derived salivary exosomes are novel diagnostic biomarkers of oral squamous cell carcinoma. Egypt Dent J. 2021; 67: 367-377.
88. Ueda S, Hashimoto K, Miyabe S, Hasegawa S, Goto M, Shimizu D, et al. Salivary NUS1 and RCN1 levels as biomarkers for oral squamous cell carcinoma diagnosis. In vivo. 2020; 34: 2353-2561.
89. He L, Ping F, Fan Z, Zhang C, Deng M, Cheng B, et al. Salivary exosomal miR-24-3p serves as a potential detective biomarker for oral squamous cell carcinoma screening. Biomed Pharmacother. 2020; 121: 109553.
90. Liu CJ, Chen JH, Hsia SM, Liao CC, Chang HW, Shieh TM, et al. Salivary LDOC1 is a gender-difference biomarker of oral squamous cell carcinoma. Peer J. 2019; 7: e6732.
91. Márton IJ, Horváth J, Lábiscsák P, Márkus B, Dezső B, Szabó A, et al. Salivary IL-6 mRNA is a robust biomarker in oral squamous cell carcinoma. J Clin Med. 2019; 8: 1958.
92. Yap T, Koo K, Cheng L, Vella LJ, Hill AF, Reynolds E, et al. Predicting the Presence of Oral Squamous Cell Carcinoma Using Commonly Dysregulated MicroRNA in Oral SwirlsOSCC Prediction from MicroRNA in Oral Swirls. Can Prev Res. 2018; 11: 491-502.
93. Gai C, Camussi F, Broccoletti R, Gambino A, Cabras M, Molinaro L, et al. Salivary extracellular vesicle-associated miRNAs as potential biomarkers in oral squamous cell carcinoma. BMC Cancer. 2018; 18: 1-11.
94. Piyarathne NS, Weerasekera MM, Fonseka PFD, Karunatilleke AHTS, Liyanage RLPR, Jayasinghe RD, et al. Salivary interleukin levels in oral squamous cell carcinoma and oral epithelial dysplasia: findings from a sri Lankan study. Cancers. 2023; 15: 1510.
95. Chu HW, Chang KP, Yen WC, Liu HP, Chan XY, Liu CR, et al. Identification of salivary autoantibodies as biomarkers of oral cancer with immunoglobulin A enrichment combined with affinity mass spectrometry. Proteomics. 2023; 23: 2200321.
96. Shabbir A, Waheed H, Ahmed S, Shaikh SS, Farooqui WA. Association of salivary Cathepsin B in different histological grades among patients presenting with oral squamous cell carcinoma. BMC Oral Health. 2022; 22: 63.
97. Man QW, Li RF, Bu LL, Zhao Y, Liu B. Salivary non‐apoptotic tumoral microvesicles: A potential progressive marker in oral cancer patients. J Cell Mol Med. 2022; 26: 5955-5965.
98. Shin YJ, Vu H, Lee JH, Kim HD. Diagnostic and prognostic ability of salivary MMP-9 for oral squamous cell carcinoma: A pre-/post-surgery case and matched control study. PLoS One. 2021; 16: e0248167.
99. Saleem Z, Shaikh AH, Zaman U, Ahmed S, Majeed MM, Kazmi A, et al. Estimation of salivary matrix metalloproteinases-12 (MMP-12) levels among patients presenting with oral submucous fibrosis and oral squamous cell carcinoma. BMC Oral Health. 2021; 21: 205.
100. Jain A, Kotimoole CN, Ghoshal S, Bakshi J, Chatterjee A, Prasad TSK, et al. Identification of potential salivary biomarker panels for oral squamous cell carcinoma. Scientific Reports. 2021; 11: 3365.
101. Salarić I, Karmelić I, Lovrić J, Baždarić K, Rožman M, Čvrljević I, et al. Salivary melatonin in oral squamous cell carcinoma patients. Scientific Reports. 2021; 11: 13201.
102. Sivadasan P, Gupta MK, Sathe G, Sudheendra H, Sunny SP, Renu D, et al. Salivary proteins from dysplastic leukoplakia and oral squamous cell carcinoma and their potential for early detection. J Proteomics. 2020; 212: 103574.
103. Singh P, Verma JK, Singh JK. Validation of Salivary markers, IL-1β, IL-8 and Lgals3bp for detection of oral squamous cell carcinoma in an Indian population. Sci Rep. 2020; 10: 1-9.
104. Smriti K, Ray M, Chatterjee T, Shenoy RP, Gadicherla S, Pentapati KC, et al. Salivary MMP-9 as a biomarker for the diagnosis of oral potentially malignant disorders and oral squamous cell carcinoma. Asian Pacific J Can Prevention (APJCP).. 2020; 21: 233.
105. Chi LM, Hsiao YC, Chien KY, Chen SF, Chuang YN, Lin SY, et al. Assessment of candidate biomarkers in paired saliva and plasma samples from oral cancer patients by targeted mass spectrometry. J Proteomics. 2020; 211: 103571.
106. Scholtz B, Vo Minh D, Kiss C, Tar I, Kumar A, Tőzsér J, et al. Examination of oral squamous cell carcinoma and precancerous lesions using proximity extension assay and salivary RNA quantification. Biomedicines. 2020; 8: 610.
107. Feng Y, Li Q, Chen J, Yi P, Xu X, Fan Y, et al. Salivary protease spectrum biomarkers of oral cancer. Int J Oral Sci. 2019; 11: 1-11.
108. Wang K, Shen Y, Xu J, Li Z, Liu Y, Yu C, et al. Evaluation of synucleinγ levels by novel monoclonal antibody in saliva and cancer tissues from oral squamous cell carcinoma patients. Neoplasma. 2020; 67: 707-713.
109. Hsu CW, Chang KP, Huang Y, Liu HP, Hsueh PC, Gu PW, et al. Proteomic profiling of paired interstitial fluids reveals dysregulated pathways and salivary NID1 as a biomarker of oral cavity squamous cell carcinoma. Mol Cell Proteomics. 2019; 18: 1939-1949.
110. Abbas MJ, Al-Rawi NA, Al-Duboni GI. Assessment of interleukin-10 and interferon-gamma with oral squamous cell carcinoma patients compared with healthy subjects as a prediction for early detection and monitor treatment response. Mustansiria Dent J. 2019; 16: 48-52.
111. Ankita K, Shwetha V, Vanitha S, Sujatha SR, Nagaraju R, Pavan KT. Assessment of salivary endothelin-1 in patients with leukoplakia, submucous fibrosis, oral cancer and healthy individuals–a comparative study. J Stomato, Oral Maxillofac Surg. 2019; 120: 326-331.
112. Chu HW, Chang KP, Hsu CW, Chang IYF, Liu HP, Chen YT, et al. Identification of salivary biomarkers for oral cancer detection with untargeted and targeted quantitative proteomics approaches. Mol Cell Proteomics. 2019; 18: 1796-1806.
113. Gupta A, Tripathi A, Patil R, Kumar V, Khanna V, Singh V. Estimation of salivary and serum basic fibroblast growth factor in treated and untreated patients with oral squamous cell carcinoma. J Oral Biol Craniofac Res. 2019; 9: 19-23.
114. Heawchaiyaphum C, Pientong C, Phusingha P, Vatanasapt P, Promthet S, Daduang J, et al. Peroxiredoxin-2 and zinc-alpha-2-glycoprotein as potentially combined novel salivary biomarkers for early detection of oral squamous cell carcinoma using proteomic approaches. J Proteomics. 2018; 173: 52-61.
115. Zheng J, Sun L, Yuan W, Xu J, Yu X, Wang F, et al. Clinical value of Naa10p and CEA levels in saliva and serum for diagnosis of oral squamous cell carcinoma. J Oral Patho Med. 2018; 47: 830-835.
116. Lee L, Wong Y, Hsiao H, Wang Y, Chan M, Chang K. Evaluation of saliva and plasma cytokine biomarkers in patients with oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2018; 47: 699-707.
117. Singh HP. Estimation of salivary biomarkers in patients with squamous cell carcinoma. Int J Clin Diagnos Patho. 2018; 1: 29-31.
118. Shan J, Sun Z, Yang J, Xu J, Shi W, Wu Y, et al. Discovery and preclinical validation of proteomic biomarkers in saliva for early detection of oral squamous cell carcinomas. Oral Dis. 2019; 25: 97-107.
119. Ameena M, Rathy R. Evaluation of tumor necrosis factor: Alpha in the saliva of oral cancer, leukoplakia, and healthy controls: A comparative study. J Int Oral Health. 2019; 11: 92.
120. Ishikawa S, Sugimoto M, Konta T, Kitabatake K, Ueda S, Edamatsu K, et al. Salivary metabolomics for prognosis of oral squamous cell carcinoma. Front Oncol. 2022; 11: 5633.
121. Tantray S, Sharma S, Prabhat K, Nasrullah N, Gupta M. Salivary metabolite signatures of oral cancer and leukoplakia through gas chromatography-mass spectrometry. J Oral Maxillofac Patho (JOMFP).. 2022; 26: 31.
122. De Sá Alves M, de Sá Rodrigues N, Bandeira CM, Chagas JFS, Pascoal MBN, Nepomuceno GLJT, et al. Identification of possible salivary metabolic biomarkers and altered metabolic pathways in South American patients diagnosed with oral squamous cell carcinoma. Metabolites. 2021; 11: 650.
123. Sridharan G, Ramani P, Patankar S, Vijayaraghavan R. Evaluation of salivary metabolomics in oral leukoplakia and oral squamous cell carcinoma. J Oral Patho Med. 2019; 48: 299-306.
124. Mujawar SJ, Suchitra G, Kosandal KA, Choudhari S, Inamdar NA, Ahmed KB. Evaluation of salivary gamma-glutamyl transpeptidase as a biomarker in oral squamous cell carcinoma and precancerous lesions. J Oral Maxillofac Patho (JOMFP).. 2020; 24: 584.
125. Abdelkawy M, El Refai S, Shaker OG, Elbattawy W. Malondialdehyde and nitrous oxide as salivary biomarkers for malignant and premalignant oral lesions. Adv Dent J. 2020; 2: 117-128.
126. Tiwari P, Khajuria N, Metgud R. Estimation of serum and salivary albumin and uric acid levels in oral submucous fibrosis and oral squamous cell carcinoma: a biochemical study. Int J Res Health Allied Sci. 2019; 5: 5-9.
127. Piao Y, Jung SN, Lim MA, Oh C, Jin YL, Kim HJ, et al. A circulating microRNA panel as a novel dynamic monitor for oral squamous cell carcinoma. Sci Rep. 2023; 13: 2000.
128. He T, Guo X, Li X, Liao C, Wang X, He K. Plasma-derived exosomal microRNA-130a serves as a noninvasive biomarker for diagnosis and prognosis of oral squamous cell carcinoma. J Oncol. 2021; 2021: 5547911.
129. Bolandparva F, Nasab MSH, Mohamadnia A, Garajei A, Nasab AF, Bahrami N. Early diagnosis of oral squamous cell carcinoma (OSCC) by miR-138 and miR-424 -5p expression as a cancer marker. Asian Pac J Cancer Prev. 2021; 22: 2185.
130. Shao T, Huang J, Zheng Z, Wu Q, Liu T, Lv X. SCCA, TSGF, and the long non-coding RNA AC007271. 3 are effective biomarkers for diagnosing oral squamous cell carcinoma. Cell Physiol Biochem. 2018; 47: 26-38.
131. Schneider A, Victoria B, Lopez YN, Suchorska W, Barczak W, Sobecka A, et al. Tissue and serum microRNA profile of oral squamous cell carcinoma patients. Sci Rep. 2018; 8: 675.
132. Chang YA, Weng SL, Yang SF, Chou CH, Huang WC, Tu SJ, et al. A three–microRNA signature as a potential biomarker for the early detection of oral cancer. Int J Mol Sci. 2018; 19: 758.
133. Gautam SS, Singh RP, Karsauliya K, Sonker AK, Reddy PJ, Mehrotra D, et al. Label-free plasma proteomics for the identification of the putative biomarkers of oral squamous cell carcinoma. J Proteomics. 2022; 259: 104541.
134. Usman M, Ilyas A, Syed B, Hashim Z, Ahmed A, Zarina S. Serum HSP90-alpha and oral squamous cell carcinoma: a prospective biomarker. Protein Pept Lett. 2021; 28: 1157-1163.
135. Zhang M, Chen X, Chen H, Zhou M, Liu Y, Hou Y, et al. Identification and validation of potential novel biomarkers for oral squamous cell carcinoma. Bioengineered. 2021; 12: 8845-8862.
136. Li X, Liu L, Li N, Jia Q, Wang X, Zuo L, et al. Metabolomics based plasma biomarkers for diagnosis of oral squamous cell carcinoma and oral erosive lichen planus. J Cancer. 2022; 13: 76.
137. Faedo RR, da Silva G, da Silva RM, Ushida TR, da Silva RR, Lacchini R, et al. Sphingolipids signature in plasma and tissue as diagnostic and prognostic tools in oral squamous cell carcinoma. Biochim Biophys Acta Mol Cell Biol Lipids. 2022; 1867: 159057.
138. Abulaiti Z, Chen L, Xiao Q, Aimaier A, Ma Y, He S, et al. PLCE1 as a diagnostic and prognostic biomarker by promoting the growth and progression of oral squamous cell carcinoma. J Oral Patho Med. 2022; 51: 771-779.
139. Sun Y, Zhou Q, Sun J, Bi W, Li R, Wu X, et al. DDX59-AS1 is a prognostic biomarker and correlated with immune infiltrates in OSCC. Front Genet. 2022; 13: 892727.
140. Hu X, Xiong H, Wang W, Huang L, Mao T, Yang L, et al. Study on the expression and function of smad family member 7 in oral submucous fibrosis and oral squamous cell carcinoma. Arch Oral Biol. 2020; 112: 104687.
141. Li L, Zhang ZT. Hsa_circ_0086414 Might Be a Diagnostic Biomarker of Oral Squamous Cell Carcinoma. Med Sci Monit. 2020; 26: e919383.
142. Ries J, Baran C, Wehrhan F, Weber M, Motel C, Kesting M, et al. The altered expression levels of miR-186, miR-494 and miR-3651 in OSCC tissue vary from those of the whole blood of OSCC patients. Cancer Biomarkers. 2019; 24: 19-30.
143. Yanagiya M, Dawood RI, Maishi N, Hida Y, Torii C, Annan DA, et al. Correlation between endothelial CXCR7 expression and clinicopathological factors in oral squamous cell carcinoma. Patho Int. 2021; 71: 383-391.
144. Li Y, Cao X, Li H. Identification and validation of novel long non-coding RNA biomarkers for early diagnosis of oral squamous cell carcinoma. Front Bioeng and Biotechnol. 2020; 8: 256.