**6. Buccal mucosa cancer and molecular markers**

Estimates based on weighted averages of data from Bangalore, Mumbai, Bhopal, Chennai, and Delhi show that buccal mucosa carcinoma has an incidence of 4.0% of all malignancies in males and 3.5% of all malignancies in females. Buccal mucosa cancer is a dissimilar disease biologically, as compared to rest of head and neck cancer, and requires great care [41]. The buccal tumor was reported to differ from other tumors by early stage less often and arises from premalignant tissue with abnormal clinical appearances, which may prevent earlier diagnosis and referral from primary care [42].

Van't Veer et al. showed the ability of gene expression profiles to classify tumors into clinically appropriate groups and to predict the outcome by using supervised statistical analyses [43]. Individuals whose primary tumors bore the metastases-related gene expression program had significantly shorter survival times compared with individuals whose tumors needed it [44].

Importantly, candidate-gene approach study had reported genetic alterations in surgical resection margins in head and neck squamous cell carcinoma (HNSCC) from different disease sites, e.g., oral cavity, pharynx/hypopharynx, and larynx [45–47]. Markedly genetic alterations identified in HNSCC encompassed over-expression of eIF4E [48], TP53, and CDKN2A/ P16 proteins [49].

A prognostic value with disease-free and overall survival was shown in a study of gene expression profile of three genes (GLUT3, HSAL2, and PACE4) were correlated with different clinical parameters [39]. A 4-gene signature (MMP1, COL4A1, THBS2, and P4HA2) for calculation of recurrence in OSCC had been studied in whole-genome expression profiling experiment and a meta-analysis of five microarray datasets developed [35].

Known risk factors like areca nut and betel quid reported to contain genotoxic, cytotoxic, and ability to stimulate human buccal mucosal fibroblast proliferation [50]. It was conveyed to act synergistically in the pathogenesis of oral submucous fibrosis and head and neck cancer [51]. Other risk factors such as arecoline, safrole, and nicotine, which are released in saliva during betel quid chewing plus cigarette smoking, inhibit collagen phagocytosis by fibroblast [52].

Majority of head and neck cancers are preceded by a period during which the affected epithelium shows evidence of epithelial dysplasia, although this may not always be clinically apparent [8]. Several studies have exposed great inter- and intra-examiner variability in the assessment of the presence or absence and the grade of oral epithelial dysplasia [53–56], the kappa values, in general, showing poor to a moderate bargain among examiners.

Five-year survival with single modality treatment of 19–20% was observed in patients with T3 and T4 stages [57]. Diaz and others had shown that the relapse amount was up to 45% in patients with early stage disease [58], and relapse rate in patients with nodes demanding some form of adjuvant treatment in early disease and high-risk tumors.

Mishra et al. had reported the relation between treatment failure and tumor thickness in a series of 176 patients with early buccal mucosa cancer [59]. Tumor thickness of more than 4 mm was found to be connected with lymph-node metastasis. In another study, tumor thickness of more than 5 mm was linked with nodal metastasis [60]. There are few studies described in the literature that associate the prognostic factors linked with clinical result of buccal cancer.

The molecular changes between the tumor subtypes are often accompanied by differences in clinical features, such as statistically robust differences in relapse-free and overall survival [61], and many studies found handfuls of specific genes whose expression is linked with prognosis [62].

**Figure 3** demonstrates the etiopathogenesis of OSCC.

Chennai were higher in both sexes among all of the states in India [37]. Currently, there are no markers that can consistently predict malignant progression in oral dysplastic lesions. Recurrent disease after surgery and radiotherapy is hard to salvage because of availability of earlier markers to predict the stage of disease [38]. It was reported that variability in the clinical course of patients remains unexplained and conventional clinicopathological parameters fail to answer all questions. Identification of novel prognostic factors may allow a rational selection of the most appropriate therapeutic options for individual patients [39]. Oral tumor thickness and other prognostic factors were found to be not correct predictors of relapse, and most of the study was not adequately powered to drought a definite conclusion. Clinicopathological parameters such as the TNM system, which are generally used as a basis for therapeutic decisions, frequently fail to predict the biologic behavior of the tumors or the patients' outcome [40]. ICMR guideline on buccal mucosa carcinoma highlights that new

prognostic factors for buccal mucosa cancer are the very important need to manage it.

Estimates based on weighted averages of data from Bangalore, Mumbai, Bhopal, Chennai, and Delhi show that buccal mucosa carcinoma has an incidence of 4.0% of all malignancies in males and 3.5% of all malignancies in females. Buccal mucosa cancer is a dissimilar disease biologically, as compared to rest of head and neck cancer, and requires great care [41]. The buccal tumor was reported to differ from other tumors by early stage less often and arises from premalignant tissue with abnormal clinical appearances, which may prevent earlier

Van't Veer et al. showed the ability of gene expression profiles to classify tumors into clinically appropriate groups and to predict the outcome by using supervised statistical analyses [43]. Individuals whose primary tumors bore the metastases-related gene expression program had significantly shorter survival times compared with individuals whose tumors needed it [44]. Importantly, candidate-gene approach study had reported genetic alterations in surgical resection margins in head and neck squamous cell carcinoma (HNSCC) from different disease sites, e.g., oral cavity, pharynx/hypopharynx, and larynx [45–47]. Markedly genetic alterations identified in HNSCC encompassed over-expression of eIF4E [48], TP53, and CDKN2A/

A prognostic value with disease-free and overall survival was shown in a study of gene expression profile of three genes (GLUT3, HSAL2, and PACE4) were correlated with different clinical parameters [39]. A 4-gene signature (MMP1, COL4A1, THBS2, and P4HA2) for calculation of recurrence in OSCC had been studied in whole-genome expression profiling

Known risk factors like areca nut and betel quid reported to contain genotoxic, cytotoxic, and ability to stimulate human buccal mucosal fibroblast proliferation [50]. It was conveyed to act synergistically in the pathogenesis of oral submucous fibrosis and head and neck cancer [51].

experiment and a meta-analysis of five microarray datasets developed [35].

**6. Buccal mucosa cancer and molecular markers**

diagnosis and referral from primary care [42].

6 Prevention, Detection and Management of Oral Cancer

P16 proteins [49].

Using high-throughput analysis of multiple surgical margins and matched oral squamous cell carcinoma to classify deregulated genes with prognostic value for recurrence need to be carried out. Presence of epithelial dysplasia or tumor cells in the surgical resection margins is linked with significant risk (66%) of local recurrence [63]. However, even with histologically normal surgical margins, 10–30% of OSCC patients will still have local recurrence [64]. Gene expression profiling by high-throughput technologies has proven to be valuable tools for prediction of outcome and progression in human malignancies including head and neck cancer [65].

To impact the survival of buccal cancer patients, molecular markers must be identified, which will help target tumors with a propensity for metastatic spread. There are numerous reports on the request of molecular biological markers for the valuation of cancer risk [66]. Molecular changes in oral pre-malignancy and head and neck cancer are influenced by differences in the ethnic and etiologic characteristics in different parts of the world [67].

Despite having poor clinical risk factors, patients who need chemotherapy will have enormous potential for better individualization of treatment options in breast cancer therapy where the clinical utility of gene signatures are playing a important contribution and proved to reliably identify patients in whom adjuvant chemotherapy is certainly not indicated [68].

**Figure 3.** The etiopathogenesis of OSCC.

A specific tumor marker is not clinically available for the discovery of cancer at an early and possibly curative stage. Lymph-node metastasis is the main step in tumor progression and a risk factor for reappearance subsequent to surgery. Cluster analysis, part of data analysis of microarray, clearly parted cases with lymph-node metastasis from those without metastasis. Data indicated that sorting of patients into high- and low-risk subgroups on the basis of the prognosis summary may be useful means of guiding adjuvant therapy in patients with lymph-node positive breast cancer.

**Figure 4** shows the mechanism of oral squamous carcinoma.

Patients who needed adjuvant chemotherapy but also those who did not need adjuvant chemotherapy, leading to a reduction in the number of women who would otherwise receive chemotherapy without compromising long-term clinical outcome was done using the 70-gene signature [69].

Netherlands Cancer Institute in Amsterdam (NKI) calculated expression of 70 genes was found to be statistically significantly linked with disease outcome, as defined by the presence of distant metastasis within 5 years. Metastases have also been found in the absence of clinically obvious primary tumors [70]. Ability to form distant metastases is a concern of particular method of transformation as contrasting to a selection process auxiliary the metastatic phenotype per se.

**7. Head and neck cancer and research hypothesis**

devices are being developed by investigators.

**Figure 4.** The mechanism of oral squamous carcinoma.

As the tools to categorize precancerous lesions in the mouth remain to improve, fewer men will die needlessly from head and neck cancer. Researchers are now harnessing the power of nanotechnology science to engineer strategies to investigate human fluids and tissues for abnormal molecules that are suggestive of a developing oral tumor. To detect abnormal cells and proteins in saliva that are associated with a developing oral tumor in-office diagnostic

Introductory Chapter: Head and Neck Cancer http://dx.doi.org/10.5772/intechopen.86272 9

Determination of any signature genes are most important in the cascade of events driving metastasis along with tumor behavior is warranted. Bieche and others reported a 3-gene expression profile, which distinguished subgroups of patients with good, intermediate, and poor outcomes [71].

**Figure 4.** The mechanism of oral squamous carcinoma.

A specific tumor marker is not clinically available for the discovery of cancer at an early and possibly curative stage. Lymph-node metastasis is the main step in tumor progression and a risk factor for reappearance subsequent to surgery. Cluster analysis, part of data analysis of microarray, clearly parted cases with lymph-node metastasis from those without metastasis. Data indicated that sorting of patients into high- and low-risk subgroups on the basis of the prognosis summary may be useful means of guiding adjuvant therapy in patients with

Patients who needed adjuvant chemotherapy but also those who did not need adjuvant chemotherapy, leading to a reduction in the number of women who would otherwise receive chemotherapy without compromising long-term clinical outcome was done using the 70-gene

Netherlands Cancer Institute in Amsterdam (NKI) calculated expression of 70 genes was found to be statistically significantly linked with disease outcome, as defined by the presence of distant metastasis within 5 years. Metastases have also been found in the absence of clinically obvious primary tumors [70]. Ability to form distant metastases is a concern of particular method of transformation as contrasting to a selection process auxiliary the metastatic phenotype per se. Determination of any signature genes are most important in the cascade of events driving metastasis along with tumor behavior is warranted. Bieche and others reported a 3-gene expression profile, which distinguished subgroups of patients with good, intermediate, and poor outcomes [71].

lymph-node positive breast cancer.

**Figure 3.** The etiopathogenesis of OSCC.

8 Prevention, Detection and Management of Oral Cancer

signature [69].

**Figure 4** shows the mechanism of oral squamous carcinoma.
