## 1 Introduction
[25] comparing biopsy samples, saliva, and swabs has identified key differences in microbial profiles. Biopsy samples, which represent localized lesions, often showed specific microbial communities such as _Fusobacterium nucleatum_ and _Treponema denticola_, whereas saliva and swab samples provided a broader, less specific overview of oral microbial diversity. These differences underline the complementary value of these sampling methods in understanding the microbiome's role in OPMD and OSCC. Recent studies have demonstrated that alterations in the oral microbiome can contribute to the pathogenesis and progression of these conditions, highlighting the potential for microbiome analysis as a diagnostic and prognostic tool [6; 18]. Emerging evidence also suggests that the oral microbiome can influence the efficacy of cancer therapies. For example, the presence of certain bacterial species has been linked to resistance to chemotherapy and radiotherapy in OSCC patients, highlighting the potential of microbiome modulation as an adjunctive treatment to improve therapeutic outcomes [26]. Specific bacterial species such as _Fusobacterium nucleatum_ and _Porphyomonas gingivalis_ have been associated with OSCC, suggesting that targeted microbiome profiling could enhance early detection and personalized treatment strategies [9; 22; 23]. This approach underscores the potential of microbiome profiling as a non-invasive diagnostic and prognostic tool in clinical practice. However, factors such as sampling methods, microbial diversity, host-microbe interactions, and the influence of environmental and lifestyle factors are critical to understanding the complex relationship between the oral microbiome and oral carcinogenesis [27; 28]. The heterogeneity in sample collection techniques--ranging from saliva, over swabs, to tissue biopsies--cansignificantly impact the microbial composition and subsequent analyses. While saliva and swabs provide less invasive alternatives, biopsy samples offer critical insights into the localized tumor microenvironment, capturing unique microbial-host interactions and lesion-specific microbial communities associated with OPMD and OSCC [19]. Furthermore, the dynamic nature of oral microbiome, influenced by diet, oral hygiene practices, and systemic health, necessitates comprehensive and longitudinal studies to delineate causative relationships. Moreover, technological advancements and methodological challenges in microbiome research emphasize the need for standardized protocols and robust bioinformatic analyses [29; 30]. High-throughput sequencing technologies and advanced computational tools have revolutionized our ability to profile microbial communities with unprecedented depth and accuracy. However, interpreting these complex datasets requires meticulous bioinformatics workflows to account for potential biases and confounding factors. While salivary sampling offers a non-invasive alternative for microbiome analysis, this review focuses on biopsy sampling for several reasons. First, biopsy samples allow for direct microbiome profiling at the site of pathological changes, providing more precise insights into localized microbial interactions within OPMD and OSCC lesions. Saliva represents a pooled sample of the entire oral cavity and may dilute or obscure microbial signatures specific to lesions, limiting its diagnostic specificity [31; 32]. Second, biopsy samples can capture intricate host-microbe interactions within the tumor microenvironment, which are critical for understanding mechanisms of carcinogenesis [33; 34]. Finally, while biopsies are more invasive, they are typically performed as part of standard diagnostic procedures in suspected OPMD or OSCC cases [35; 36]. Therefore, utilizing these samples for microbiome analysis leverages existing clinical workflows without necessitating additional procedures. This review aims to evaluate the significance of oral microbiome research specifically in biopsy samples of OPMD and OSCC.