## 1 Introduction  
Oral potentially malignant disorders (OPMD) encompass a variety of clinical entities that carry a risk of progression to oral squamous cell carcinoma (OSCC), a subtype of head and neck squamous cell carcinoma (HNSCC) [1; 2; 3]. These disorders, including leukoplakia, erythroplakia, oral lichen planus, proliferative verrucous leukoplakia, actinic, cheilitis and oral submuc fibrosis, present unique challenges in clinical management and prognosis due to their unpredictable nature. OSCC represents a significant portion of head and neck cancers, characterized by high morbidity and mortality rates [1; 4; 5]. The transformation from OPMD to OSCC is influenced by multiple factors, including genetic mutations, environmental exposures, and the microbial environment of the oral cavity. The oral microbiome, comprising diverse microbial communities, plays a critical role in maintaining oral health and might play a pivotal role in the pathogenesis of OSCC through mechanisms like enhancing inflammation, modulating the immune system, and direct microbial carcinogenesis, which all lead to promoting carcinogenic pathways and influencing the tumor microenvironment [6; 7; 8; 9; 10; 11]. For instance, chronic inflammation induced by pathogenic bacteria like _Porphyomonas gingivalis_ and _Fusobacterium nucleatum_ has been shown to promote inflammatory responses that can lead to DNA damage, creating a pro-carcinogenic environment and subsequently predisposing to cancer development [8; 12; 13; 14; 15]. Immune modulation by the oral microbiome is another critical aspect, as it influences the tumor microenvironment by interacting with immune cells and other components within the oral cavity. This interaction can modulate the immune response, potentially allowing tumor cells to evade immune surveillance. The interaction between microbial communities and the host's immune system can either promote or inhibit carcinogenesis. Dysbiosis, or an imbalance in the microbial community, may lead to immune dysregulation, facilitating the persistence and progression of OPMDs [6; 16; 17; 14; 18]. In addition to bacterial communities, the oral microbiome includes other microbial groups, such as fungi, viruses, and protozoa, that are increasingly recognized for their potential roles in OPMD and OSCC pathogenesis. Research showed that fungi like _Candida albicans_ and viruses such as Epstein-Barr virus and human papillomavirus (HPV) may interact with bacterial communities to exacerbate dysbiosis, influence inflammatory responses, and impact disease progression [19]. Despite their relevance, most studies have concentrated on bacterial microbiomes, highlighting the need for broader research into these other microbial groups in OPMD and OSCC biopsy samples. Analysis of the microbial profiles in OSCC patients has revealed significant differences compared to healthy controls, indicating that specific microbial signatures could potentially serve as biomarkers for early detection and prognosis of OSCC [20]. Direct microbial carcinogenesis involves the production of carcinogenic compounds by specific bacterial species, promoting carcinogenic pathways by metabolizing dietary components. For instance, _Fusobacterium nucleatum_ has been implicated in the promotion of tumorigenesis through its ability to invade epithelial cells and modulate cellular pathways involved in cell proliferation and apoptosis by modulating the E-cadherin/\(\beta\)-catenin signaling pathway, a mechanism that might also be relevant in OSCC [20; 21]. Studies have shown that dysbiosis may contribute to the pathogenesis of OPMD, making it crucial to understand these microbial alterations for early detection and prevention [22; 23]. Research indicates that microbial signatures differ significantly between healthy tissue and OPMD lesions. For example, the presence of _Treponema denticola_ and _Tannerella forythia_ has been linked to an increased risk of malignant transformation in patients with leukoplakia and erythrophakia [24]. Moreover, study conducted by [PERSON] et al.