Microbial dysbiosis in oral potentially malignant disorders: A systematic review - 26/06/26

Doi : 10.1016/j.jormas.2026.102876

Keerthika R ^a, Akhilesh Chandra ^b,^⁎ , Subhadeep Pal ^c, Harshita Tiwari ^c, Amlendu Shekhar ^d,^{^{1
0000–0002–5171–2486.}}, Rahul Agarwal ^e

^a Senior Resident, Unit of Oral Pathology and Microbiology, Faculty of Dental Sciences, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India

^b Associate Professor, Unit of Oral Pathology and Microbiology, Faculty of Dental Sciences, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India

^c Junior Resident, Unit of Oral Medicine and Radiology, Faculty of Dental Sciences, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India

^d Senior Resident, Unit of Oral Medicine and Radiology, Faculty of Dental Sciences, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India

^e Professor, Unit of Oral Pathology and Microbiology, Faculty of Dental Sciences, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India

^⁎ Corresponding author.

Abstract

Background

Oral potentially malignant disorders (OPMDs) including oral leukoplakia (OLK), proliferative verrucous leukoplakia (PVL), and oral verrucous hyperplasia (OVH) pose variable malignant transformation risk to oral squamous cell carcinoma (OSCC), yet the role of microbial dysbiosis in their progression remains ambiguous.

Objectives

To elucidate microbial shifts in OPMDs, their association with dysplasia progression and malignant transformation, highlighting prospects for early detection and risk stratification.

Material and methods

A comprehensive literature search was conducted across scientific databases up to May 2025. Studies investigating microbial dysbiosis in OLK, PVL, or OVH using 16S rRNA sequencing, metagenomic, or transcriptomic analyses were included. Risk of bias was assessed using the modified Newcastle-Ottawa scale.

Results

OPMDs showed inconsistent alpha diversity and distinct beta diversity compared to controls. Microbial composition differed by lesion type: OLK was enriched with Fusobacterium periodonticum, Porphyromonas pasteri, Streptococcus, and Haemophilus; PVL with Campylobacter concisus, Leptotrichia, and Haemophilus parainfluenzae ; and OVH with Porphyromonas gingivalis, Tannerella forsythia, and Saccharibacteria TM7. High-risk OLK showed reduced diversity and enrichment of Fusobacterium nucleatum, Parvimonas, and Streptococcus infantis. Malignant transformation revealed lesion-specific shifts, including increased Fusobacterium, Capnocytophaga and Porphyromonas in OLK-OSCC, while Neisseria was specifically enriched in progressive OLK lesions, Treponema and Campylobacter in PVL-OSCC, and Capnocytophaga sputigena and Prevotella oris in OVH - OSCC.

Conclusion

This review highlights the pivotal role of microbial dysbiosis in the evolution of OPMDs to malignancy. Distinct microbial signatures across OLK, PVL, and OVH may serve as biomarkers for disease stratification and early detection of high-risk lesions.

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Keywords : Malignant transformation, Metagenomics, Microbial dysbiosis, Oral leukoplakia, Oral microbiome, Oral potentially malignant disorders, Oral squamous cell carcinoma, Oral verrucous hyperplasia, Proliferative verrucous leukoplakia, 16S rRNA sequencing