Microbial dysbiosis and host–microbe interactions in proliferative verrucous leukoplakia: insights into carcinogenic potential

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Abstract
Proliferative verrucous leukoplakia (PVL) is a rare and aggressive oral potentially malignant disorder (OPMD) characterized by multifocal keratotic plaques, progressive expansion, high recurrence, and a strong risk of malignant transformation. Although its etiology remains unclear, recent evidence emphasizes the role of the oral microbiome as a key factor in disease progression. Alterations in microbial diversity and ecological balance create a shift toward dysbiosis, supporting a chronic inflammatory microenvironment that favors epithelial transformation. Specific taxa, including Fusobacterium and Porphyromonas, have been implicated in biofilm formation, immune evasion, and modulation of epithelial signaling pathways. These interactions highlight the potential of microbial communities to drive oncogenic processes through host–microbe crosstalk. Advanced methodological approaches such as metagenomics, functional microbiome profiling, and multi-omics integration provide novel opportunities to unravel the mechanisms of dysbiosis in PVL. Beyond pathogenesis, microbiome research opens perspectives for the identification of predictive biomarkers, targeted prevention, and microbiome-based therapeutics. This review synthesizes current insights into the microbial basis of PVL and outlines future directions aimed at improving understanding of host–microbe interactions and their role in oral carcinogenesis. Relevant literature was identified through PubMed and Web of Science searches (1985–2025) using terms related to PVL, oral leukoplakia, OPMD, oral microbiome, and oral squamous cell carcinoma. In conclusion, current evidence suggests that while microbial dysbiosis is not an isolated driver, it likely synergizes with genetic, epigenetic, and immunological factors in PVL progression, offering opportunities for biomarker discovery and novel therapeutic strategies. This study also provides a potential direction for the early diagnosis of PVL and the development of microecologically targeted interventions.

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