Mechanisms and markers of malignant transformation of oral submucous fibrosis

Abstract

Oral submucous fibrosis (OSF) is a chronic premalignant disease associated with betel quid chewing. Epidemiological studies indicate that there are approximately 5 million individuals suffering from OSF worldwide, with a concerning malignancy transformation rate of up to 4.2 %. When OSF progresses to oral squamous cell carcinoma (OSCC), the 5-year survival rate for OSCC drops to below 60 %. Therefore, early screening and diagnosis are essential for both preventing and effectively treating OSF and its potential malignant transformation. Numerous studies have shown that the malignant transformation of OSF is associated with various factors, including epigenetic reprogramming, epithelial-mesenchymal transition, hypoxia, cell cycle changes, immune regulation disturbances, and oxidative damage. This review article focuses on the unraveling the potential mechanisms underlying the malignant transformation of OSF, as well as the abnormal expression of biomarkers throughout this transformative process, with the aim of aiding early screening for carcinogenic changes in OSF. Furthermore, we discuss the significance of utilizing blood and saliva components from patients with OSF, along with optical diagnostic techniques, in the early screening of OSF malignant transformation.

Keywords: Biomarkers; Malignant transformation; Oral squamous cell carcinoma; Oral submucous fibrosis.

Fig. 1

(A) Oral submucosal fibrosis. Fibrosis of the left buccal area characterized by grayish-white mucosal alterations and palpable fibrous striated changes. (b) Oral squamous carcinoma with oral submucosal fibrosis. Fibrosis of the right buccal area displaying grayish-white mucosal changes and ulcerated surfaces in the posterior cheek. This conditions presents with a hard base and an indistinct boundary upon touch. This study received prior approval from the Ethics Committee of Xiangya Stomatological Hospital of Hunan Central South University, China. The study was conducted in compliance with established ethical guidelines and with the informed consent of participants. (Original figures).

Fig. 2

Hematoxylin-eosin staining was performed on samples from patients with oral submucosal fibrosis and oral squamous cell carcinoma with oral submucosal fibrosis. (a) The lesion at the earliest stage. Some fine collagen fibers appear, with obvious edema accompanied by neutrophil infiltration (hematoxylin–eosin, × 100). (b) The lesion in its early stage. A band of vitreous degeneration can be seen in collagen fibers immediately below the epithelium, along with inter-collagen fiber edema with lymphocytic infiltration (hematoxylin–eosin, × 100). (c) The lesion in the middle stage. Moderate vitreous changes can be observed in collagen fibers, along with mild edema and lymphocytic and plasma cell infiltration (hematoxylin–eosin, × 100). (d) The lesion in its late stage. All collagen fibers exhibit a glassy appearance with noticeable narrowing or occlusion of blood vessels (hematoxylin–eosin, × 100). (e) Oral squamous cell carcinoma with oral submucosal fibrosis (hematoxylin–eosin, × 100). This study received a prior approval from the Ethics Committee of Xiangya Stomatological Hospital of Hunan Central South University, China. The study was conducted in compliance with established ethical guidelines and with the informed consent of participants. (Original figures).

Fig. 3

The mechanisms and markers of the malignant transformation of oral submucosal fibrosis. The process of the malignant transformation of oral submucosal fibrosis into oral squamous cell carcinoma has been associated with epigenetic modifications, epithelial–mesenchymal transition, cell cycle alterations, hypoxia and neoangiogenesis, immunomodulatory disturbances, and oxidative damage. In the diagram, the black arrow represents inclusion or grading, the red arrow represents rising, and the blue arrow represents falling.