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Role of Oral Microbiome Signatures in Diagnosis and Prognosis of Oral Cancer
Open accessAbstract
Despite advancement in cancer treatment, oral cancer has a poor prognosis and is often detected at late stage. To overcome these challenges, investigators should search for early diagnostic and prognostic biomarkers. More than 700 bacterial species reside in the oral cavity. The oral microbiome population varies by saliva and different habitats of oral cavity. Tobacco, alcohol, and betel nut, which are causative factors of oral cancer, may alter the oral microbiome composition. Both pathogenic and commensal strains of bacteria have significantly contributed to oral cancer. Numerous bacterial species in the oral cavity are involved in chronic inflammation that lead to development of oral carcinogenesis. Bacterial products and its metabolic by-products may induce permanent genetic alterations in epithelial cells of the host that drive proliferation and/or survival of epithelial cells. Porphyromonas gingivalis and Fusobacterium nucleatum induce production of inflammatory cytokines, cell proliferation, and inhibition of apoptosis, cellular invasion, and migration thorough host cell genomic alterations. Recent advancement in metagenomic technologies may be useful in identifying oral cancer–related microbiome, their genomes, virulence properties, and their interaction with host immunity. It is very important to address which bacterial species is responsible for driving oral carcinogenesis. Alteration in the oral commensal microbial communities have potential application as a diagnostic tool to predict oral squamous cell carcinoma. Clinicians should be aware that the protective properties of the resident microflora are beneficial to define treatment strategies. To develop highly precise and effective therapeutic approaches, identification of specific oral microbiomes may be required. In this review, we narrate the role of microbiome in the progression of oral cancer and its role as an early diagnostic and prognostic biomarker for oral cancer.
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“Additional changes throughout one's life, including to dietary habits, age, hygiene regimens, and behaviors (such as tobacco and alcohol use), also influence changes to the oral microbiome.132”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [132]
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“More than 700 bacterial species inhabit the oral cavity, so the influence of bacteria cannot be avoided (Chattopadhyay et al., 2019).”
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Insights into the oral microbiota in human systemic cancers
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“It possesses the ability to directly influence host cells by binding to E-cadherin in both normal and cancerous epithelial cells using FadA.”
BackgroundZanetta, P., Squarzanti, D. F., Sorrentino, R., Rolla, R., Valletti, P. A., Garzaro, M., Dell’Era, V., Amoruso, A., & Azzimonti, B. (2021) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2021.1872487 · Cited by 15
Li, J., Sun, S., Li, J., Zhao, X., Li, Z., Sha, T., & Cui, Z. G. (2021) · Neoplasma · doi:10.4149/neo_2021_210421n544 · Cited by 15
Myrcene exerts anti-tumor effects on oral cancer cells in vitro via induction of apoptosis
Wu, Z., Li, Z., & Liang, Y. (2022) · Tropical Journal of Pharmaceutical Research · doi:10.4314/tjpr.v21i5.4 · Cited by 15
“Oral cancer is one of the frequently reported human cancers [1].”
BackgroundComparative analysis of oral microbiome from Zang and Han populations living at different altitudes
Yu, H., Tang, C., Du, Q., Zhou, X., Peng, X., & Cheng, L. (2020) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2020.104986 · Cited by 15
Oral microbiota: the overlooked catalyst in cancer initiation and progression
Wang, X., He, X., & Zhong, B. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1479720 · Cited by 15
Mazul, A. L., Hartman, C. M., Mowery, Y. M., Kramer, J. R., White, D. L., Royse, K. E., Raychaudhury, S., Sandulache, V. C., Ahmed, S. T., Zevallos, J. P., et al. (2022) · Cancer · doi:10.1002/cncr.34387 · Cited by 14
“The oral cavity is generally within homeostasis with the more than 700 documented bacterial species that comprise the oral microflora.(24) Disruption of the oral ecosystem— including microbiota and immune components resulting from chronic immunosuppression— could lead to premalignant and malignant lesions.”
BackgroundAsili, P., Mirahmad, M., Rezaei, P., Mahdavi, M. R., Larijani, B. A., & Tavangar, S. M. (2023) · Journal of Gastrointestinal Cancer · doi:10.1007/s12029-022-00901-4 · Cited by 14
“Aerobic and anaerobic organisms collaborate to develop oral biofilms that protect them from environmental changes [21].”
Oral dysbiosis in the onset and carcinogenesis of oral epithelial dysplasia: A systematic review
Shen, X., Zhang, Y., Zhu, J., & Xu, B. (2023) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2023.105630 · Cited by 17
Zanetta, P., Squarzanti, D., di Coste, A., Amoruso, A., Pane, M., & Azzimonti, B. (2023) · Biomedicines · doi:10.3390/biomedicines11030859 · Cited by 16
İlhan, B., Vural, C., Gürhan, C., Vural, C., Veral, A., Wilder-Smith, P. B. B., Özdemir, G., & Güneri, P. (2023) · Cancers · doi:10.3390/cancers15215251 · Cited by 15
“Bacteria are the predominant members of the oral microbiome with approximately 1000 bacterial strains being cultivated to date [3,4].”
BackgroundA Comparison of the Oral Microbiota in Healthy Dogs and Dogs with Oral Tumors
Lisjak, A., Lopes, B. C., Pilla, R., Nemec, A., Suchodolski, J. S., & Tozon, N. (2023) · Animals · doi:10.3390/ani13233594 · Cited by 14
“It also prevents the activity of the tumor suppressor gene p53 [30,32].”
BackgroundMatsui, K., Tani, R., Yamasaki, S., Ito, N., Hamada, A., Shintani, T., Otomo, T., Tokumaru, K., Yanamoto, S., & Okamoto, T. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25116077 · Cited by 16
The impact of probiotics on oral cancer: Mechanistic insights and therapeutic strategies
Priya, K. S. L., Datchanamoorthy, M., Ravi, S. S. S., Vajravelu, L. K., Lathakumari, R. H., & Malavika, G. (2025) · Oral Oncology Reports · doi:10.1016/j.oor.2025.100715 · Cited by 14
Intini, R., Balsells, S., Bagán, L., Fortuna, G., Sroussi, H., & Sebastián, J. V. B. (2025) · Frontiers in Oral Health · doi:10.3389/froh.2025.1600090 · Cited by 14
“Although the association between oral microbial imbalances and OSCC has been increasingly recognized, the precise contribution of different microbial taxa to OPMD initiation, progression, and malignant transformation remains poorly understood (26 – 28).”
Starska, K. (2025) · Cancers · doi:10.3390/cancers17213478 · Cited by 14
“The severity of changes in the exposed epithelium and gingival tissues has been found to increase with the presence of the oral commensal microbial communities in oral mucosa [126,127].”
Ahmad, S., Jayamanne, D. T., Bergamin, S., Lawless, A. K., Guminski, A. D., Lee, A. V., Yuile, A., Wheeler, H., Eade, T., Back, M., et al. (2025) · Cancers · doi:10.3390/cancers17162667 · Cited by 18
“Porphyromonas gingivalis , a known periodontal pathogen, was also enriched in HNSCC samples, consistent with its established involvement in immune evasion, inflammation, and cancer progression [40].”
Zhou, M., Liu, Y., Yin, X., Gong, J., & Li, J. (2025) · Discover Oncology · doi:10.1007/s12672-025-03440-z · Cited by 12
“…invasiveness through multiple mechanisms: (1) upregulation of matrix metalloproteinases (MMP-1, MMP-9, MMP-10), leading to extracellular matrix degradation [61]; (2) FimA-mediated epithelial-mesenchymal transition [62, 63]; and (3) dysregulation of cell cycle progression via p53 and PI3K pathways.”
Galeana-Patiño, C. E., Ortiz, M. I., Cariño‐Cortés, R., Santillán, I. C. L., Castro‐Rosas, J., Gómez‐Aldapa, C. A., & Muñoz‐Pérez, V. M. (2023) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201024666230213094953 · Cited by 12
Oral–Gut–Estrobolome Axis May Exert a Selective Impact on Oral Cancer
Tatullo, M., Nor, J. E., Orrù, G., Piattelli, A., Cascardi, E., & Spagnuolo, G. (2024) · Journal of Dental Research · doi:10.1177/00220345241236125 · Cited by 12
“In conclusion, we can argue that oral pathogens associated with poor oral hygiene have a multifaceted impact on local and systemic inflammation, impairing the oral and gut microbiota, as well as creating more favorable conditions to develop some forms of oral cancer (Chattopadhyay et al. 2019).”
BackgroundAdtani, P., Al-Bayati, S. A. A. F., & El‐Sayed, W. (2025) · Pharmaceuticals · doi:10.3390/ph18030393 · Cited by 12
“To-bacco and alcohol are significant risk factors in the majority of OSCC cases, followed by viral infections, such as HPV, which contribute to the rising incidence of OSCC among young individuals, especially non-smokers [20,21,22]. young individuals, especially non-smokers [20–22].”
Liu, Y., Liu, H., Rong, Y., Shi, Q., Yang, Q., Li, H., Zhang, Z., & Tao, J. (2023) · Journal of Oral Microbiology · doi:10.1080/20002297.2023.2264619 · Cited by 13
Role of Nanozymes in Oral Cancer the Road Ahead
Augustine, D., Sowmya, S. D., Gujjar, N., Pushpalatha, C., & Haragannavar, V. C. (2022) · Topics in Catalysis · doi:10.1007/s11244-022-01729-9 · Cited by 11
“Additionally, risk of OSCC is increased due to the colonisation of fungus Candida albicans [3, 15].”
BackgroundSami, A., Elimairi, I., Ryan, C. A., Stanton, C., Patangia, D. V., & Ross, R. P. (2023) · Scientific Reports · doi:10.1038/s41598-023-32892-y · Cited by 11
Metatranscriptome analysis of blood in healthy individuals and irritable bowel syndrome patients
Jagare, L., Rozenberga, M., Silamiķelis, I., Ansone, L., Elbere, I., Brīvība, M., Megnis, K., Konrāde, I., Birka, I., Straume, Z., et al. (2023) · Journal of Medical Microbiology · doi:10.1099/jmm.0.001719 · Cited by 11
Jiang, Q., Liu, X., Yang, Q.-F., Chen, L., & Yang, D. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.774453 · Cited by 12
“Porphyromonas gingivalis and Fusobacterium nucleatum induce production of inflammatory cytokines, cell proliferation, and inhibition of apoptosis, cellular invasion, and migration thorough host cell genomic alterations (Chattopadhyay et al., 2019).”
BackgroundZhao, T., Hu, H., Chen, X., Liu, Y., Wang, H., & Li, X. (2022) · PubMed Central · Cited by 11
The oral microbiome in the context of systemic disease
Leonov, G. E., Varaeva, Y. R., Николаевна, Л. Е., & Starodubova, A. V. (2023) · Voprosy Pitaniya · doi:10.33029/0042-8833-2023-92-4-6-19 · Cited by 16
Shridhar, K., Aggarwal, A., Rawal, I., Gupta, R., Masih, S., Mehrotra, R., Gillespie, T. W., Dhillon, P. K., Michaud, D. S., Prabhakaran, D., et al. (2021) · PLoS ONE · doi:10.1371/journal.pone.0251017 · Cited by 10
Molecular insights into the role of electronic cigarettes in oral carcinogenesis
Maan, M., Abuzayeda, M., Kaklamanos, E. G., Jamal, M., Dutta, M., & Moharamzadeh, K. (2023) · Critical Reviews in Toxicology · doi:10.1080/10408444.2023.2190764 · Cited by 10
“…by inducing inflammation, metabolism of pre-carcinogenic substances, changes in tumor micro-environment and epigenetic modulations of host cells (Lax 2005; Tribble et al. 2013; Inaba et al. 2014; Perera et al. 2018; S.-F. Yang, Huang, et al. 2018; Yang, Lee, et al. 2018; Chattopadhyay et al. 2019).”
BackgroundAnjali, K., Manzoor, M., Suryavanshi, M. V., Rudrapathy, P., Rekha, P. D., Das, R., Hameed, A., & Arun, A. B. (2023) · FEMS Microbiology Letters · doi:10.1093/femsle/fnad111 · Cited by 10
Taj, Z., & Chattopadhyay, I. (2024) · Peptide Science · doi:10.1002/pep2.24348 · Cited by 10
Self-citationHasan, F., Yuliana, L. T., Budi, H. S., Ramasamy, R., Ambiya, Z. I., & Ghaisani, A. M. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e32102 · Cited by 10
Liu, J., Yue, Q., Zhang, S., Xu, J., Jiang, X., Su, Q., Sun, L., Li, B., Li, K., Su, L., et al. (2024) · Folia Microbiologica · doi:10.1007/s12223-024-01185-w · Cited by 11
“Some strains of Streptococcus and Actinomyces regulate the pH of oral biofilms by metabolizing arginine to produce bases (Chattopadhyay et al. 2019; Sedghi et al. 2021).”
Impact of Novel Foods on the Human Gut Microbiome: Current Status
Martínez, A., Velázquez, L., Díaz, R., Huaiquipán, R., Pérez, I., Muñoz, A., Valdés, M., Sepúlveda, N., Paz, E. A., & Quiñones, J. (2024) · Microorganisms · doi:10.3390/microorganisms12091750 · Cited by 12
“In addition, eHOMD includes genomes of a new phylum of nano-microorganisms, known as “candidate phyla radiation”, of bacterial organisms including 35 phyla and consists of more than 15% of the domain Bacteria [87].”
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Li, S., Lu, Y., Song, Y., Zhu, X., Xiang, C., Zuo, E., & Cheng, X. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/9529814 · Cited by 10
“Approximately 405,000 new oral cancer cases are reported worldwide annually, with the highest incidence reported in Sri Lanka and India [1, 2].”
RetractedBolesina, N., Gatti, G., de Blanc, S. A. L., Dhooge, S., Rocha, D., Fernández, E. A., Ferreyra, R., Palla, V., Grupe, V., Morelatto, R., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.941667 · Cited by 10
Oral Microbiome Traits of Type 1 Diabetes and Phenylketonuria Patients in Latvia
Abola, I., Gudrā, D., Ustinova, M., Frīdmanis, D., Emulina, D. E., Skadiņš, I., Brinkmane, A., Lauga-Tuņina, U., Gailīte, L., & Auzenbaha, M. (2023) · Microorganisms · doi:10.3390/microorganisms11061471 · Cited by 10
“Of all the listed genera, only Haemophilus has been described as a classical oral microbiome exemplar, with an increased abundance previously being reported in healthy individuals [56,57], in contrast to our results.”
ResultDong, J., Li, Y., Xiao, H., Cui, M., & Fan, S. (2021) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2020.0476 · Cited by 11
Koth, V. S., Salum, F. G., de Figueiredo, M. A. Z., & Cherubini, K. (2020) · Clinical Oral Investigations · doi:10.1007/s00784-020-03585-x · Cited by 10
Gut–Oral Microbial Dysbiosis: A Correlated Ecosystem
Siddiqui, Z. R., Rahman, S., Verma, N., Srivastava, A. K., Jahan, N., Mohanty, S., & Suman, S. (2025) · Advanced Gut & Microbiome Research · doi:10.1155/agm3/7351229 · Cited by 10
“While these bacterial groups are commonly present, each niche also showcases its unique bacterial makeup [23].”
Metadata
- Authors
- Chattopadhyay, I., Verma, M., & Panda, M.
- Affiliations
- Central University of Tamil Nadu (IN)
- National Institutes of Health (US)
- Corresponding author
- Chattopadhyay, Indranil
- Venue
- Technology in Cancer Research & Treatment
- Publisher
- SAGE Publications
- Published
- 2019-01-01
- Volume
- 18
- Pages
- 1533033819867354-1533033819867354
- ISSN
- 1533-0338 (ISSN-L)
- 1533-0346
- PMC
- PMC6676258
- OpenAlex
- W2965423269
- Cited by
- 407
- References
- 118
- Citations by year
- 2026: 32 · 2025: 72 · 2024: 76 · 2023: 68 · 2022: 72 · 2021: 63 · 2020: 24
- FWCI
- 5.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Technology in Cancer Research & Treatment (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Dentistry › General Dentistry › Oral Health Pathology and Treatment
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Keywords
- oral microbiota, oral cancer, oral squamous cell carcinoma, tumor markers, early diagnosis, prognosis, Porphyromonas gingivalis, Fusobacterium nucleatum, oral carcinogenesis, chronic inflammation, alcohol and tobacco use, areca nut, commensal bacteria, metagenomics, host-microbe interactions
- MeSH terms
- Humans, Inflammation, Mouth Neoplasms, Prognosis, Saliva, Porphyromonas gingivalis, Fusobacterium nucleatum, Cell Proliferation, Carcinogenesis, Microbiota
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