. 2023 Dec 10;96(1):250–280. doi: 10.1111/prd.12542

TABLE 5.

Oral microbiome‐based biomarker for OSCC

Authors/Year	Source of biomarker	Method	Sample size	Microbiome	Findings
Katirachi et al. ¹⁴⁰	N/D	Systematic Review and meta‐analysis	5007	Human papillomavirus	6% (95% CI; 3%–10%) HPV prevalence in OSCC
Peter et al. ²²⁶	Swabs, Saliva, Tissue, Oral rinse and Tissue scraping	Systematic review and meta‐analysis	970	Fusobacterium, Peptostreptococcus, and Parvimonas	Enriched in OSCC compared to Control
Peter et al. ²²⁶	Swabs, Saliva, Tissue, Oral rinse and Tissue scraping	Systematic review and meta‐analysis	970	Haemophilus and Granulicatella	Decreased in OSCC compared to Control
Mauceri et al. ²²⁷	Saliva	Systematic review	1335	Porphyromonas gingivalis, Fusobacterium nucleatum, Neisseria flavescens, Fusobacterium periodonticum, Prevotella intermedia and Campylobacter spp,	Enriched in OSCC compared to Control, but it was not possible to profile a specific microbiota associated with OSCC due to the great heterogeneity of the studies
Mun et al. ¹³²	Saliva, Tissue, Oral rinse and Oral swab	Systematic review	2809	Fusobacteria, Firmicutes, and Bacteroidetes	Enriched in OSCC compared to Control; All the studies identified microbial dysbiosis to be associated with OSCC
Melo et al. ¹⁴¹	Tissue	Systematic review	383	Human papillomavirus	4.4% of the patients were HPV positive; None of the studies found had a control group
Lafuente Ibañez de Mendoza et al. ²²⁸	In vitro and In vivo	Systematic review	N/A	Porphyromonas gingivalis	Enriched in OSCC compared to Control; Bacterium involved in epithelial‐mesenchymal transition of malignant epithelial cells, neoplastic cell growth, proliferation and invasion
Ramos et al. ²²⁹	Saliva, Tissue, Oral rinse and Oral swab	Systematic review	859	Fusobacterium nucleatum subsp. Polymorphum and Pseudomonas aeruginosa	Enriched in OSCC compared to Control; Corroborated dysbiosis in OSCC. Enrichment of taxa associated with inflammation and production of acetaldehyde
She et al. ¹³⁹	Tissue	Systematic review	1119	Epstein–Barr virus	Positive association with an increased risk of OSCC
Vyhnalova et al. ¹³⁶	N/D	Review article	N/A	Candida albicans, Candida etchellsii, Candida famata, Gibberella, Hannaella, Rhodotorula, mucilaginosa	Enriched in OSCC compared to Control
Vyhnalova et al. ¹³⁶	N/D	Review article	N/A	Aspergillus tamarii, Alternaria, Cladosporium, Halotolerans, Emericella, Malassezia restricta, Pichia anomala, Trametes	Decreased in OSCC compared to Control
Radaic et al. ⁸	Saliva and tissues	Review article	N/A	Treponema denticola, Porphyromonas gingivalis, Fusobacteria Nucleatum, Tannarella Forsythia, Lactobacillus spp., Capnocytophaga gingivalis, Prevotella melaninogenica, Streptococcus mitis. Fusobacteria genera	Enriched in OSCC compared to Control
Radaic et al. ⁸	Saliva and tissues	Review article	N/A	Streptococcus, Capnocytiphaga, Neisseria, Haemophillus and Aggreggatibacter	Decreased in OSCC compared to Control
Radaic & Kapila ¹²⁰	N/D	Review article	N/A	Candida mycotype, Treponema denticola, Porphyromonas gingivalis, Fusobacteria Nucleatum, Tannarella Forsythia Capnocytophaga gingivalis, Prevotella melaninogenica, Streptococcus mitis	Enriched in OSCC compared to Control
Radaic & Kapila ¹²⁰	N/D	Review article	N/A	Malassezia mycotype, Streptococcus, Neisseria, Haemophillus and Aggreggatibacter	Decreased in OSCC compared to Control
Chattopadhyay et al. ¹³³	N/D	Review article	N/A	P. melaninogenica, Capnocytophaga gingivalis, Lactobacillus vaginalis, L. gasseri: L. johnsonii, L. fermentum, L. salivarius, L. rhamnosus, Fusobacterium nucleatum, F. periodonticum, Streptococcus vestibularis, S. mitis, S. salivarius, Prevotella oris, and Rothia mucilaginosa	Enriched in OSCC compared to Control
Chattopadhyay et al. ¹³³	N/D	Review article	N/A	Aggregatibacter, Lautropia, Haemophillus, Neisseria, Leptotrichia, P. jejuni: P. melaninogenica, and Prevotella pallens	Decreased in OSCC compared to Control
Perera et al. ¹²⁸	Saliva, swab, and tissues	Review article	885	Fusobacterium, Porphyromonas, Actinomyces, Propionibacterium spp., Candida albicans, Porphyromonas gingivalis, Streptococcus anginosus, Capnocytophaga gingivalis, Prevotella melaninogenica, Streptococcus mitis, Micrococcus luteus, Prevotella melaninogenica, Exiguobacterium oxidotolerans, Fusobacterium naviforme, Staphylococcus aureus, Veillonella parvula, Bacteroides fragilis, Ralstonia insidiosa, Fusobacterium naviforme, Peptostreptococcus micros, Clavibacter michiganensis subsp. tessellarius, Capnocytophaga sp. oral strain S3, Prevotella sp. oral clone BE073, Parvimonas sp. oral taxon 110, Eubacterium infirmum, Eubacterium brachy, Gemella haemolysans, Gemella morbillorum, Gemella sanguinis, Johnsonella ignava, Streptococcus parasanguinis I Peptostreptococcus stomatis, Streptococcus gordonii and Streptococcus salivarius	Taxa associated with OSCC
Yang et al. ²³⁰	Saliva and whole blood	16S Sequencing	428	Lachnoanaerobaculum, Kingella, Parvimonas	Enriched in OSCC compared to Control and correlated to genes in regulation of oncogenic and angiogenic responses
Gopinath et al. ²³¹	Whole mouth fluid and Oral Swab	16S Sequencing	94	Enterobacteriae, Neisseria, Streptococcus and Fusobacteria, Prevotella, Treponema, Sphingomonas, Meiothermus, and Mycoplasma	Enriched in OSCC compared to Control; Tumor surfaces elevated abundances of Porphyromonas, Enterobacteriae, Neisseria, Streptococcus and Fusobacteria, whereas Prevotella, Treponema, Sphingomonas, Meiothermus and Mycoplasma genera were significantly more abundant in deep tissue.
Gopinath et al. ²³²	Whole mouth fluid	16S Sequencing	74	Porphyromonas	Correlated to OSCC
				Megasphaera, unclassified Enterobacteria, Salmonella and Prevotella	Correlated to OPMD
				Streptococcus, Rothia and Fusobacterium	Correlated to Control
Ganly et al. ²³³	Oral rinse	16S Sequencing	38	Fusobacterium, Prevotella, Alloprevotella	Enriched in OSCC compared to Control
Ganly et al. ²³³	Oral rinse	16S Sequencing	38	Streptococcus	Decreased in OSCC compared to Control
Yang et al. ²³⁴	Oral rinse	16S Sequencing	248	Fusobacterium periodonticum, Parvimonas micra, Streptococcus constellatus, Haemophilus influenza, and Filifactor alocis (in contrast to decrease of Streptococcus mitis, Haemophilus parainfluenzae, Porphyromonas pasteri, Veillonella parvula)	Enriched in OSCC compared to Control; Higher complexity of oral microbiota communities in stage 4 patients
Hsiao et al. ²³⁵	Saliva	16S Sequencing	289	Prevotella tannerae, Fusobacterium nucleatum, and Prevotella intermedia	Enriched in OSCC compared to Control
Hsiao et al. ²³⁵	Saliva	16S Sequencing	289	Streptococcus tigurinus	Decreased compared to Control
Lee et al. ²³⁶	Saliva	16S Sequencing	376	Bacillus, Enterococcus, Parvimonas, Peptostreptococcus, and Slackia	Enriched in OSCC compared to Control
Al‐Hebshi et al. ²³⁷	Swabs and tissues	16S Sequencing	20 OSCC biopsies and 20 swabs	F. nucleatum and P. aeruginosa	Enriched in OSCC compared to Control
Wang et al. ²³⁸	Saliva and oral swab	16S Sequencing	55	Porphyromonas and Solobacterium g	Enriched in OSCC compared to Control
Wang et al. ²³⁸	Saliva and oral swab	16S Sequencing	55	Haemophilus, Corynebacterium, Cellulosimicrobium, and Campylobacter	Decreased in OPMD compared to Control
Hu et al. ²³⁹	Non‐stimulated saliva	16S Sequencing	35	Haemophilus, and Bacillus	Bacillus enriched in OSCC compared to Control, while Haemophilus Enriched in OPMD compared to Control
Hu et al. ²³⁹	Non‐stimulated saliva	16S Sequencing	35	Streptococcus	Decreased in OPMD and OSCC
Yost et al. ²⁴⁰	Oral swab	Metatranscriptome sequencing	15	Genera Fusobacteria, Selenomonas, Capnocytophaga, Dialister, and Johnsonella (genus Bacillus; species Porphyromonas catoniae, Kingella denitricans, Capnocytophaga gingivalis, among others, were associated with healthy, tumor‐matching sites)	Enriched in OSCC compared to Control
Zhao et al. ²⁴¹	Oral swab	16S Sequencing	80	Fusobacterium, Dialister, Peptostreptococcus, Filifactor, Peptococcus, Catonella and Parvimonas	Enriched in OSCC compared to Control
Nie et al. ²⁴²	Tissue	16S Sequencing	305	Fusobacterium, Prevotella, Porphyromonas, Campylobacter, Aggregatibacter, Lautropia, Asteroleplasma, Parvimonas, Peptostreptococcus, Pyramidobacter, Roseburia, and Propionibacterium	Enriched in OSCC compared to Control. The microbiome was highly correlated with tumor clinicopathological features, with several genera
de Abreu et al. ¹⁴⁸	Tissue	Nested PCR	90	Human papillomavirus	3.3% of the OSCC patients were positive for HPV. All cases were HPV‐16
Nieminen et al. ²⁴³	Tissue	Immunohistochemistry	149	Treponema denticola	Dentilisin present in OSCC and the majority of orodigestive tumor samples
Perera et al. ²⁴⁴	Tissue	ITS2 sequencing	52	C. albicans, C. etchellsii, and Hannaella luteola–like species	Enriched in OSCC compared to Control
Perera et al. ²⁴⁴	Tissue	ITS2 sequencing	52	A Hanseniaspora uvarum–like species, Malassezia spp., Aspergillus tamarii, Cladosporium halotolerans, and Alternaria alternata	Decreased in OSCC compared to Control
Listyarifah et al. ²⁴⁵	Tissue	Immunohistochemistry	60	Treponema Denticola	Dentilisin present in 95% of OSCC tumor samples and 40% were immunopositive for dentilisin.
Shin et al. ²⁴⁶	Tissue	16S Sequencing	72	Fusobacteria, Firmicutes, Actinobacteria, Proteobacteria and Streptococcus	Fusobacterium enriched in OSCC compared to Control
Shin et al. ²⁴⁶	Tissue	16S Sequencing	72	Streptococcus	Decreased in OSCC compared to Control
Kikuchi et al. ¹⁴⁴	Tissue	PCR	233	Epstein–Barr virus	50.2% of OSCC; 66.7% of severe dysplasia; 43.1% of mild dysplasia were positive for EBV.
Mokhtari & Beiraghdar ¹⁴²	Tissue	PCR	60	Herpes simplex‐1	5% of the OSCC patients were potivite for HSV
Saravani et al. ¹⁴³	Tissue	qPCR	48	Human Cytomegalovirus	6.3% of the OSCC patients were positive for HCMV
Harrandah et al. ¹³⁵	In vivo	ELISA and Western blot	N/A	Fusobacteria	Mice infected with bacteria developed significantly larger and more numerous lesions compared to those not infected.
Kamarajan et al. ¹³⁴	In vivo and in vitro	Western blot	N/A	Treponema denticola, Fusobacterium nucleatum, and Prophyromonas gingivalis	Periodontal pathogens promote cancer aggressivity in mice via TLR2/MyD88 triggered activation of integrin/FAK signaling
Gallimidi et al. ¹²⁹	In vivo and in vitro	Immunohistochemistry	N/A	Fusobacterium nucleatum, and Prophyromonas gingivalis	Periodontal pathogens promote cancer aggressivity in mice; Increased STAT3 and IL‐6 levels in infected mice compared to control