**Abstract**

Diagnosing and treating lesions of the mouth and gums is challenging for most clinicians because of the wide variety of disease processes that can present with similar appearing lesions and the fact that most clinicians receive inadequate training in mouth diseases. Oral cancer, a common lesion in oral cavity, is not correctly diagnosing a clinical picture of an early squamous cell carcinoma. The prevalence of oral cancer continues to rise worldwide, related to the increase in consumption of tobacco, alcohol and other carcinogenic products. However, there has also been a significant reduction in mortality due to increasing awareness, early diagnosis and advances in treatments. This chapter is an attempt to provide a comprehensive update encompassing the spectrum of etiologic/risk factors, current clinical diagnostic tools, management philosophies, and molecular biomarkers and progression indicators of oral cancer.

**Keywords:** oral cancer, oral cavity cancer, head and neck cancer, squamous cell carcinoma, oral lesions

#### **1. Introduction**

Oral cancer is one of the most prevalent diseases worldwide, accounting for 30–40% of the head and neck cancer. There are an estimated 200,000 cases of oral cancer worldwide each year, which cause an estimated 100,000 deaths [1]. Particularly, these are malignant lesions of the oral structure including anterior two thirds of tongue, lips (upper lip, lower lip and edge), the upper and lower gingiva, retromolar trigone, buccal mucosa and floor of the mouth. The most common histopathology of oral cancer is squamous cell carcinoma, contributing to approximately 90% of cases. Multidisciplinary oncologic treatment, such as surgery, radiation therapy and chemotherapy, plays important roles in treatment for oral cavity cancer [2].

#### **2. Oral cavity anatomy**

The oral cavity is composed of the mucosa of the lips (not outer, dry lips), the buccal mucosa, the anterior tongue, the floor of the mouth, the hard palate and the

upper and lower gingiva. The anterior boundary is determined by the portion of the upper lip connected to the lower lip (wet mucosa). While, the posterior side is bound by the V-groove of the tongue, the anterior tonsillar pillars (palatoglossus muscles) and the posterior margin of the hard palate. Inferiorly, the oral cavity is formed by mylohyoid muscles. Additionally, the lateral border of the oral cavity spans between the buccomasseteric area (buccal mucosa) and retromolar trigone (**Figure 1**).

relationship between clinical pathology and prognosis. Therefore, the HPV test has

*Bar chart of region-specific incidence age-standardized rates by sex for cancers of the lip and Oral cavity in*

*Oral Cancer: The State of the Art of Modern-Day Diagnosis and Treatment*

*DOI: http://dx.doi.org/10.5772/intechopen.91346*

A total of 90 to 95% of all malignant lesions in the oral cavity are the squamous cell carcinoma. Moreover, it can be classified into three main groups: good differentiation (above 75% keratinization), moderate differentiation (25–75% keratinization) and poorly differentiated tumors (below 25% keratinization). Besides, less common types of histopathology could be mentioned such as verrucous carcinoma (a variant of squamous cell carcinoma), adenocarcinoma, adenoid cystic carcinoma

On the other hand, the squamous cell carcinoma of the head and neck ordinarily undergo several developments of precancerous lesions due to exposure to carcino-

• Oral leukoplakia is a precancerous lesion that presents as white patches in the oral mucosa. Notably, this damage is relatively common at a rate of 4% in the population [6]. Leukoplakia is divided into two types: homogenous lesions and heterogeneous lesions, in which cancer is highly induced by heterogeneous lesions. The diagnosis of leukoplakia usually relies on a biopsy to diagnose histopathology. Aside from that, biopsy is a standard criterion of the histopathological diagnosis in the clinical leukoplakia [7]. Surgery was indicated to any cases with small heterogeneous leukoplakia or lesions with severe dysplasia. Likewise, conservative treatments are regularly indicated for widespread leukoplakia or lesions with moderate or mild dysplasia [8]. Not to mention is oral proliferative verrucous leukoplakia (OPVL), a rare case found in patients. This is a malignant lesion of heterozygous leukoplakia with multifocal-type surface characteristics, slow progression and immense rate of malignant transformation. Some of the treatments such as surgery, laser,

not been recommended for oral cancer [5].

*2018. Source: GLOBOCAN 2018 [1].*

and mucoepidermoid carcinomas.

**4. Pathology**

**Figure 2.**

genic factors.

**91**

#### **3. Epidemiology and etiology of pathogenesis**

An estimated 200,000 cases of oral cancer every year worldwide resulted in around 100,000 lethal cases [1]. Oral cavity tumors frequently occur with the local invasions, destructions of the surrounding tissue and lymph node metastases, but there is not often have distant metastasis at the time of diagnosis. Smoking and alcohol assumption are two major risks of the oral squamous cell carcinoma [3]. Likewise, in Asia, especially in India, chewing nut quid is also an important key factor [4]. Furthermore, oral tobacco use, periodontal disease, radiation and immunodeficiency have been considered as risks linked to oral cancer. By the same token, sun exposure (ultraviolet radiation) is also a causal factor. Both of tobacco assumption and chewing nut quid are predominant risks of buccal mucosa cancers [3, 4]. **Figure 2** illustrates Region-Specific Incidence Age-Standardized Rates by Sex for Cancers of the Lip and Oral Cavity in 2018 [1].

Interestingly, human papillomavirus (HPV) infection, especially HPV 16, is associated with the incidence rates of tonsilloma and tongue cancer. Yet, the ratio of HPV infection related to oral cancer is significantly lower and there was an unclear

#### *Oral Cancer: The State of the Art of Modern-Day Diagnosis and Treatment DOI: http://dx.doi.org/10.5772/intechopen.91346*

#### **Figure 2.**

*Bar chart of region-specific incidence age-standardized rates by sex for cancers of the lip and Oral cavity in 2018. Source: GLOBOCAN 2018 [1].*

relationship between clinical pathology and prognosis. Therefore, the HPV test has not been recommended for oral cancer [5].

#### **4. Pathology**

upper and lower gingiva. The anterior boundary is determined by the portion of the upper lip connected to the lower lip (wet mucosa). While, the posterior side is bound by the V-groove of the tongue, the anterior tonsillar pillars (palatoglossus muscles) and the posterior margin of the hard palate. Inferiorly, the oral cavity is formed by mylohyoid muscles. Additionally, the lateral border of the oral cavity spans between the buccomasseteric area (buccal mucosa) and retromolar trigone

An estimated 200,000 cases of oral cancer every year worldwide resulted in around 100,000 lethal cases [1]. Oral cavity tumors frequently occur with the local invasions, destructions of the surrounding tissue and lymph node metastases, but there is not often have distant metastasis at the time of diagnosis. Smoking and alcohol assumption are two major risks of the oral squamous cell carcinoma [3]. Likewise, in Asia, especially in India, chewing nut quid is also an important key factor [4]. Furthermore, oral tobacco use, periodontal disease, radiation and immunodeficiency have been considered as risks linked to oral cancer. By the same token, sun exposure (ultraviolet radiation) is also a causal factor. Both of tobacco assumption and chewing nut quid are predominant risks of buccal mucosa cancers [3, 4]. **Figure 2** illustrates Region-Specific Incidence Age-Standardized Rates by Sex for

Interestingly, human papillomavirus (HPV) infection, especially HPV 16, is associated with the incidence rates of tonsilloma and tongue cancer. Yet, the ratio of HPV infection related to oral cancer is significantly lower and there was an unclear

**3. Epidemiology and etiology of pathogenesis**

Cancers of the Lip and Oral Cavity in 2018 [1].

(**Figure 1**).

**90**

**Figure 1.**

*Oral Diseases*

*Oral cavity anatomy.*

A total of 90 to 95% of all malignant lesions in the oral cavity are the squamous cell carcinoma. Moreover, it can be classified into three main groups: good differentiation (above 75% keratinization), moderate differentiation (25–75% keratinization) and poorly differentiated tumors (below 25% keratinization). Besides, less common types of histopathology could be mentioned such as verrucous carcinoma (a variant of squamous cell carcinoma), adenocarcinoma, adenoid cystic carcinoma and mucoepidermoid carcinomas.

On the other hand, the squamous cell carcinoma of the head and neck ordinarily undergo several developments of precancerous lesions due to exposure to carcinogenic factors.

• Oral leukoplakia is a precancerous lesion that presents as white patches in the oral mucosa. Notably, this damage is relatively common at a rate of 4% in the population [6]. Leukoplakia is divided into two types: homogenous lesions and heterogeneous lesions, in which cancer is highly induced by heterogeneous lesions. The diagnosis of leukoplakia usually relies on a biopsy to diagnose histopathology. Aside from that, biopsy is a standard criterion of the histopathological diagnosis in the clinical leukoplakia [7]. Surgery was indicated to any cases with small heterogeneous leukoplakia or lesions with severe dysplasia. Likewise, conservative treatments are regularly indicated for widespread leukoplakia or lesions with moderate or mild dysplasia [8]. Not to mention is oral proliferative verrucous leukoplakia (OPVL), a rare case found in patients. This is a malignant lesion of heterozygous leukoplakia with multifocal-type surface characteristics, slow progression and immense rate of malignant transformation. Some of the treatments such as surgery, laser,

radiation or bleomycin-contained-chemotherapy facilitate to temporarily control the damage. Nonetheless, the relapse rate or malignant transformation is up to 70% of patients and the lethal rate contributes to higher than 30% for around a decade [9].

• Erythroplakia, a type of relatively uncommon lesions, has a relatively high rate of malignant transformation (above 80%) [10]. This lesion can be recognized with a red strip, relatively smooth, no symptoms in the floor of the mouth, the surface of the tongue and the soft palate in elder patients routinely using tobacco and alcohol. Thus, a complete removing surgery is a major recommendation in this case [11].
