Oral Potentially Malignant Disorders: Etiology, Pathogenesis, and Transformation Into Oral Cancer

Abstract

Among oral diseases, oral cancer is a critical health issue due to its life-threatening potential. Globocan, in its 2020 report, estimated ∼0.37 million new cases of oral cancer, with the majority of them coming from the Asian continent. The WHO has anticipated a rise in the incidences of oral cancer in the coming decades. Various factors, such as genetic, epigenetic, microbial, habitual, and lifestyle factors, are closely associated with oral cancer occurrence and progression. Oral lesions, inherited genetic mutations (dyskeratosis congenital syndrome), and viral infections (HPV) are early signs of oral cancer. Lesions with dysplastic features have been categorized under oral potentially malignant disorders (OPMDs), such as oral leukoplakia, erythroplakia, oral submucous fibrosis (OSMF), and proliferative verrucous leukoplakia, are assumed to have a high risk of malignancy. The incidence and prevalence of OPMDs are recorded as being high in South-Asian countries. Early detection, prevention, and treatment of OPMDs are needed to prevent its malignant transformation into oral cancer. Many advanced diagnostic techniques are used to predict their progression and to assess the risk of malignant transformation. This communication provides insight into the importance of early detection and prevention of OPMDs.

Keywords: erythroplakia; leukoplakia; malignant transformation; oral lichen planus; oral lichenoid lesions; oral potentially malignant disorders; oral submucous fibrosis; proliferative verrucous leukoplakia.

FIGURE 1

Systematic representation of normal buccal mucosa.

FIGURE 2

Different types of OPMDs (inner circle) and common risk factors (outer rings) associated with oral cancer development.

FIGURE 3

(A) Clinical presentation of leukoplakia, a typical appearance of white patch. (B) H&E stained section (4x) showing hyperkeratinized stratified squamous epithelium.

FIGURE 4

Role of immune cells in OLP pathogenesis; (A) Immune infiltration in OLP, CD8⁺ T cells mediated hyperimmune activation leading to apoptosis of basal keratinocytes. (B) Possible mechanism of hyperimmune response in buccal mucosa, where CD8⁺ T cells are activated by oral keratinocytes and CD4⁺ T cells.

FIGURE 5

(A) Oral lichen planus (B) Hyperkeratinized stratified squamous epithelium (10x) showing basal cell degeneration at focal areas. Juxtaepithelially stroma shows presence of lymphocytes infiltration.

FIGURE 6

Hyperkeratotic epithelial cells in OSMF. Immune activation in OSMF show the presence of different types of immune infiltrates in submucous layer. Increase in fibroblast cells leads to high production of collagen fibres (brown bar) leading to fibrosis of oral mucosa.

FIGURE 7

OSMF pathogenesis: Cellular and molecular changes in buccal mucosa due to areca nut exposure.

FIGURE 8

(A) Oral submucosal fibrosis of cheek mucosa. (B) Keratinized stratified squamous epithelium (4x) showing presence of hyalinization and collagenous connective tissue stroma.

FIGURE 9

Erythroplakia patch.

FIGURE 10

(A) Proliferative verrucous leukoplakia show multifocal presence in anterior gingiva, labial vestibule extended to right and left side of gingiva. (B) Hyperkeratinized stratified squamous epithelium (4x) with verrucous like projection and inflammatory cell infiltration in lamina propria.

FIGURE 11

Clinical representation of oral lichenoid lesions.

FIGURE 12

Actinic cheilitis a typically presentation at lower lip.

FIGURE 13

Clinical presentation of palatal lesions in reverse smokers.