Genetic Revelation of the Potentially Malignant Disorders in the Oral and Maxillofacial Region

*Nitish Krishna Das, A.K.M. Shafiul Kadir, Mohammad Ullah Shemanto, Ety Akhter, Ashik Sharfaraz, Soumik Tripura, Joye Kundu and Ayesha Afrose Ura*

### **Abstract**

The oral and maxillofacial region is the site of numerous cancer forms. The most frequent cancer, which accounts for more than 90% of these tumors, is squamous cell carcinoma. Genetic changes caused by malignant transformation later result in phenotypic changes in cells. Potentially malignant disorders and circumstances can lead to the development of some malignancies, such as oral squamous cell carcinomas (OSCCs). Because OSCC and precursor lesions cannot be detected early, the 5-year survival rate for OSCC is still only about 50%. Early detection of oral cancer, particularly in the premalignant stage, can greatly reduce death and morbidity. The clinical, histological revelations and etiopathogenesis of a few potentially malignant disorders of the oral and maxillofacial region are reviewed in this chapter.

**Keywords:** mutation, genetic element, polymorphism, potentially malignant disorders, oral and maxillofacial region

### **1. Introduction**

Cancer is a collection of disorders have been designated by unusual proliferation of cells and the capacity to migrate or spread to other regions of the body [1]. According to Global Cancer Statistics 2022, more than 19.3 million (19,300,000) new cancer cases were diagnosed and recorded recently, resulting in nearly 10 million fatalities by 2020 [2]. According to projections made by the American Cancer Society, it was estimated that in the year 2022, there would be a total of 1,918,030 newly diagnosed cases of cancer and 609,360 deaths attributed to cancer in the United States [3]. Oral and maxillofacial cancer is one of the most common kinds of cancer, and it is becoming a growing concern in numerous regions of the world [4]. Oral cancer is the sixteenth most prevalent malignancy and the fifteenth leading cause of death globally, with an incidence of four cases per 100,000 people (age-adjusted), with substantial regional differences depending on gender, age groups, nations, races and ethnicities, and socioeconomic conditions [5]. Geographical location is a significant role in the

development of oral cancer since persons with poor socioeconomic class are more likely to get the disease because they are less aware of the dangers of avoidable risk factors such as tobacco, areca nut, and alcohol use [6]. In South Asian nations such as India, Sri Lanka, Pakistan, and Bangladesh, it is the most prevalent kind of oral cancer and accounts for around one-fourth of all new cases [4].

Oral cancer may originate through two primary pathways: *de novo* development or progression from potentially malignant disorders. These lesions commonly manifest as leukoplakia (characterized by a white patch), erythroplakia (characterized by a red patch), or erythroleukoplakia (characterized by a mixed red and white patch) [7]. Squamous cell carcinoma (OSCC) is the most prevalent cancer, accounting for more than 90% of all malignancies, and it develops from potentially malignant lesions and conditions in the oral and maxillofacial facial region [8]. There are several stages to the development of oral cancer from potentially malignant disorders, including genetic, epigenetic, and metabolic changes [5, 9–11]. Genetic alterations that arise during the process of carcinogenesis can manifest as various types of genomic changes, including point mutations, amplifications, rearrangements, and deletions [12]. Proto-oncogenes undergo a conversion process that leads to the formation of oncogenes. These oncogenes are responsible for modifying the protein sequences of growth-promoting proteins and factors that regulate the cell cycle. Consequently, uncontrolled cell division occurs weakening cell cohesion and causing local infiltration, which plays a crucial role in the progression from dysplasia to oral squamous cell carcinoma (OSCC) [13]. Numerous oncogenes play a vital role in cellular responses, and these include the proto-oncogene epidermal growth factor receptor (EGFR/c-erb 1), various members of the ras gene family, c-myc, int-2, hst-1, PRAD-1, bcl-1, and the growth regulator P53 [14].

The management of oral squamous cell carcinoma (OSCC) has undergone significant transformations; in recent years, primarily due to the emergence of immunotherapy, in addition to conventional approaches such as surgery, systemic therapy, and radiotherapy, either as individual therapies or in combination. Nevertheless, a significant proportion of cases are typically identified during the later stages of the ailment, resulting in a substantial reduction in the overall survival rate among affected individuals [15]. The most effective approach to preventing the transformation of cancer is through the early detection of potentially malignant disorders, which involves regular oral examinations and the removal of environmental and behavioral risk factors that are associated with such lesions [16, 17].

In this chapter, the epidemiology and clinico-histological aspects of numerous forms of potentially malignant disorders in the oral and maxillofacial region will be briefly discussed. Their risk factors, genetic and epigenetic underpinnings, early detection approaches, and therapy to prevent the development of malignancies will also be emphasized.
