Recent Advances in the Early Diagnosis of Oral Cancer : A Systematic Review

Introduction: Oral cancer survival rates are strongly dependent upon the stage in which the diagnosis is being made. Patients diagnosed with oral cancer within the localized stage have a substantially greater chance of successful treatment, and there is a greater chance of morbidity if the patient is diagnosed with cancer in later stages. Successful early detection symbolizes one of the superlative techniques which would eventually increase the oral cancer survival rate and quality of life worldwide. This study aimed to illustrate and provide awareness of current trends and recent advances in early diagnostic tools of oral cancer and to differentiate the validity of diverse initial detection methods. Methods: This research is a systematic review. The evaluation was confined to articles published in the past 15 years (i.e. 1999-2016). Searches were conducted both manually and electronically. A “manual exploration” was made by methodically examining key journals available in the library of the institution; documents and data were retrieved from the online databases PubMed and Google Scholar.Results: In total, 19 articles were reviewed. Conclusions: Oral cancer detection techniques can provide real-time diagnoses and are non-invasive. At present, large multicenter trials are necessary to determine the sensitivity and specificity of these individual and combined techniques and to evaluate and develop their ability to detect and manage potentially malignant and malicious oral lesions.

i.e. less than five years.This rate has remained lamentably low and relatively constant during the last few decades. 6This review flows with an aim and objectives as given below.

Objectives
-To illustrate and become acquainted with the trends in recent advances in early diagnostic aids of oral cancer -To recognize the validity of different early detection methods; -To outline the recommendations of the researchers on efficient early diagnostic techniques in clinics and field work.

Search Strategy and Eligibility Criteria
This systematic review was conducted on recent advances in diagnosing oral cancer.For this, a thorough literature search was carried out both manually and electronically.The databases PubMed and Google Scholar were searched using MeSH entry terms mixed with Boolean phrases 'AND' or 'OR'.Articles included were confined to the past 15 years.Duplications were discarded.Apart from the online search, articles were also collected from related journals available in the institutional library.Clear representation of the included literature and summarization of the available insights regarding the topic of interest were done following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist.

Data Collection
The basic search resulted in a total of 1,283 articles, which included mainly original articles, overviews, and reviews.Articles other than original research on human participants were excluded from the study.Articles not relevant to the topic of interest or objectives of the study were excluded.

Data Extraction and Analysis
The number of articles included at each stage based on the eligibility criteria are shown in Figure 1.After completing the search, the selected documents were summarized and categorized based on the topic and its implications.Finally, the selected articles were categorized based on indexation (Table 1).Total number of studies finally included, n=19

Duplications, n=586
Articles not relevant to the topic of interest, n=237 Articles discarded due to publication before the year 1999, n=345

Results
Finally, the total number of articles included in the study was 19.Table 1 shows that most of the articles included in the study were published in PubMed-indexed journals.Publications related to the topic of interest surged in the year 2011 (Figure 2).Table 2 shows the country wise distribution of the articles.As can be seen, the maximum number of articles was Indian-based.Table 3 shows various early diagnostic tools pertaining to oral cancer given by different authors, their comparison with the gold standard biopsy, the types of lesions that were included in the studies, sensitivity, specificity, positive predictive values, negative predictive values, and accuracy.

Discussion
-Malignancy: Inclining to become progressively worse and to result in death; having the properties of anaplasia, invasiveness, and metastasis. 7Pre-malignancy: Morphologically-altered tissue in which cancer is more likely to develop than its apparently normal counter-part1, or a generalized disturbance or a disease state which predisposes the patient to the development of a neoplasm at a particular site. 8Sensitivity: The ability of a test to correctly identify all those who have the disease, i.e. true positives.A sensitivity of 90% means that 90% of the diseased persons screened by the test will give "true positive" results, and the remaining 10% will give "false negative" results. 9Specificity: The ability of a test to correctly identify all those who do NOT have the disease, i.e. true negatives.A specificity of 90% means that 90% of the non-diseased persons will give "true negative" results, and 10% of nondiseased people screened by the test will be wrongly classified as "diseased". 9Accuracy: The extent to which the test accurately measures what it purports to measure.In other words, validity explains the ability of a test to separate or distinguish those who have the disease from those who do not28.
-Positive predictive value: Probability of patients having the disease in question when the test result is positive. 9Negative predictive value: Probability of patients not having the disease in question when the test result is negative. 9ntervallic clinical examination of the oral cavity is the mainstay for early detection of oral cancer as it has been shown to reduce mortality from oral cancer by 32% in high-risk individuals. 10With the aim of improving the efficiency of oral cancer diagnoses, advanced techniques are being developed to complement clinical examination and facilitate the identification of carcinomas in initial stages.Progression in the field of oral cancer research has led to the development of diagnostic tools at both the clinical and molecular level for the early recognition of oral cancer. 11An early recognition of these cancers helps the provision of better and faster treatment to improve prognoses to some degree.The available advanced diagnostic adjuncts are helpful tools for the early diagnosis of oral cancer. 12al Cancer Survival Rates Oral cancer survival rates are strongly reliant on the stage at diagnosis.Patients diagnosed with oral cancer at a localized stage have a considerably greater chance of successful treatment and less treatment-associated morbidity than those diagnosed at a late stage.
Improving early recognition is one of the best ways to improve survival rates and quality of life for oral cancer patients worldwide.In developing countries, oral cancer patients tend to be diagnosed at a later stage than that in developed countries.Thus, there remains a vital need to improve early detection of oral cancer and its precursors.The contemporary goal of the International Agency for Research on Cancer, American Cancer Society, and the WHO is to reduce the predicted 15 million cancer cases by a third by diagnosing and treating these cancers at their pre-neoplastic levels.Oral cancer is an ideal choice for this strategy, because the oral cavity delivers easy access for clinical scrutiny, and development of oral cancer is preceded by perceptible mucosal changes.However, only 40% of oral cancers are presently diagnosed as localized disease, which is the same rate as that of colon cancers. 2 Despite recent diagnostic and therapeutic advances, the 5-year survival rate for oral cancer has persisted at less than 50% over the last 50 years owing to the following reasons: first, the bulk of oral cancer cases, i.e. around 60% of cases, were noticed in  The 5-year recurrence-free survival rate in oral cancer patients is 80% for those diagnosed in stage I and only 20% for those diagnosed in stage IV.Moreover, diagnosis at early stages of oral cancer greatly reduces treatmentrelated morbidity and improves the long-term survival rate.Patients with a history of oral cancers are at risk of developing secondary tumors at a rate of 3.7% per year.Because of "field cancerization," one fourth of all oral cancer-related deaths are caused by secondary tumors.Hence, patients who are effectively treated for oral cancer should be closely monitored, preferably using a noninvasive diagnostic test.The lack of an early-stage diagnosis of oral cancer or diagnosis at the pre-neoplastic level impedes increasing survival rates in oral squamous cell carcinoma patients.However, poor detection rates were registered during routine clinical examination by general dentists. 2n day-to-day clinical practice, dental and medical practitioners repeatedly encounter a wide variety of oral mucosal lesions.Oral cancer is generally preceded by some benign lesions existing for a varying length of time.
Tobacco users with pre-cancerous lesions run the risk of developing oral cancer at a rate 69 times greater than those who do not have pre-cancer.The recognition and management of pre-cancer, therefore, set up a vital cancer control measure.Currently, the most efficient way of battling oral cancer is by early diagnosis followed by suitable treatment.The clinician's dilemma is how to differentiate cancerous lesions from a swarm of other illdefined lesions that also occur in the oral cavity.The majority of oral lesions are benign, but these lesions may have an appearance that may be easily confused with malignant lesions, and some are considered premalignant, because they have been statistically connected with subsequent cancerous changes.Conversely, some malignant lesions seen at an early stage may be fallacious for a benign change. 11or patients treated within one month of symptom onset, the 5-year survival rate is 86%, but this decreases to 47% at seven months after the onset of symptoms.Survival is threatened if treatment occurs after twelve months. 30The nonspecific clinical appearance of dysplastic and early malignant lesions further highlights the need to develop objective methodologies for early recognition. 31,32 rum diagnostic tests are routinely used in assessment of many systemic disorders.Saliva serves as a substitute for serum as a biologic fluid that can be scrutinized for diagnostic purposes.Saliva meets the demands for an inexpensive, noninvasive, and easy-to-use diagnostic platform.Saliva can be a superior early diagnostic biofluid because of the quantity available and the ease with which specimens are collected, stored, and transported compared to serum and urine.Its nonclotting nature offers an additional advantage by reducing the need for more manipulations. 33ome testing kits would further facilitate salivary testing as a diagnostic aid enabling patients, especially those who live far from their treatment centers, to monitor their own health at home. 34Early detection will enable up to 90% of oral cancer patients to be cured, and it facilitates a more cost effective treatment. 15he non-invasive process of saliva testing can be an alternative modality to serum testing in diagnosing and determining prognoses in oral cancer.It can also be used in the evaluation of post therapy status.

Conclusion
Informing and educating the public in matters related to well-known risk factors associated with oral cancer is necessary.Reducing the incidence of oral cancer is an aspect of achieving a healthier nation.Community action, capacity-building measures, and raising public awareness could contribute to achieving a significant reduction in incidence.Oral cancer can be detected and diagnosed in its early stages by a thorough 5-minute oral examination.Screening for oral cancer by visual examination is modest, inexpensive, and causes little discomfort.A certain proportion of cancers arise out of premalignant or potentially malignant lesions of the oral mucosa, and early diagnosis and effective treatment of these can reduce the incidence of oral cancer.Initial cancerous lesions are easier to treat than advanced lesions from the perspective of improving a patient's quality of life.Understanding the development and progression of a lesion is key in the quest for early diagnosis and prevention.Early diagnostic techniques are not only beneficial for differentiating normal mucosa from dysplastic or malicious lesions, but they also help in monitoring treatment and potential obstacles.These techniques can facilitate diagnosis in real time, and they are non-invasive.At present, large multicenter trials are necessary to determine the sensitivity and specificity of these tests, and to introduce a combination of techniques to assess.These techniques also support to improve their capability to detect and manage potentially malignant and malicious oral lesions.

Figure 1 .
Figure 1.Flow chart of the study International Journal of Medical Reviews.2017;4(4):119-125 their advanced stages (III and IV).Secondly, the maximum number of oral cancer cases runs the risk of transforming into secondary tumors ("field cancerization phenomenon") compared with other cancers.

Table 1 .
Distribution of articles based on indexation

Indexation No. of Articles PubMed 17 Non-PubMed 02 Total 19 Figure 2. Year wise distribution of articlesTable 2 .
Country wise distribution of articles

Table 3 .
Results of various early diagnostic tools given by different authors pertaining to oral cancer