Alterations of oral microbiome in oral potentially malignant disorders: a systematic review

Oral potentially malignant disorders (OPMDs), including conditions such as Oral lichen planus, Oral leukoplakia, Proliferative verrucous leukoplakia and Oral submucous fibrosis are associated with an increased risk of oral squamous cell carcinoma. Emerging evidence suggests that alterations in the oral microbiome may contribute to the pathogenesis of these disorders and their malignant transformation. This systematic review aimed to synthesize current evidence on oral microbiome composition and diversity in patients with OPMDs.

A comprehensive literature search of PubMed, Scopus, Web of Science, and Google Scholar was conducted to identify eligible human studies published through August 2025. Studies evaluating oral microbiome profiles in patients with clinically and/or histopathologically diagnosed oral potentially malignant disorders (OPMDs) were included. Data on study characteristics, sampling and analytical methods, microbial diversity, and differentially abundant taxa were extracted independently by two reviewers. Risk of bias was assessed using the Newcastle-Ottawa Scale. Owing to substantial clinical and methodological heterogeneity, findings were synthesized qualitatively.

A total of 56 studies were included, comprising 30 studies of Oral lichen planus, 9 of Oral leukoplakia, and 17 examining other OPMDs. 16srRNA sequencing was mostly used and whole unstimulated saliva was the most frequently collected specimen. The most prevalent microbial phyla identified in OPMD patients included Firmicutes, Proteobacteria, and Fusobacteria, but the direction and magnitude of changes varied across OPMD subtypes and sampling methods. Several studies reported an increase in pathogenic species such as Porphyromonas and Prevotella, while commensal bacteria like Streptococcus were less abundant. Findings concerning microbial richness and diversity were inconsistent.

Oral microbial dysbiosis is a common feature of oral potentially malignant disorders; however, a reproducible microbial signature has not yet been established. Substantial heterogeneity in study design, sampling strategies, and analytical approaches limits causal inference and clinical applicability. Future standardized longitudinal studies are needed to clarify the role of the oral microbiome in malignant transformation and its potential utility as a prognostic biomarker.

Prospero registration number: CRD42024516735.