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Wang, J.; Gao, B. Oral Microbes in Oral Squamous Cell Carcinoma. Encyclopedia. Available online: (accessed on 21 June 2024).
Wang J, Gao B. Oral Microbes in Oral Squamous Cell Carcinoma. Encyclopedia. Available at: Accessed June 21, 2024.
Wang, Jingyi, Bo Gao. "Oral Microbes in Oral Squamous Cell Carcinoma" Encyclopedia, (accessed June 21, 2024).
Wang, J., & Gao, B. (2024, January 05). Oral Microbes in Oral Squamous Cell Carcinoma. In Encyclopedia.
Wang, Jingyi and Bo Gao. "Oral Microbes in Oral Squamous Cell Carcinoma." Encyclopedia. Web. 05 January, 2024.
Oral Microbes in Oral Squamous Cell Carcinoma

Microorganisms in the oral cavity are abundant in the human body. At present, more than 700 species of oral microorganisms have been identified. Recently, a lot of literature has indicated that the oral microbiota plays an important role in the occurrence, development, and prognosis of oral squamous cell carcinoma (OSCC) through various mechanisms. And researchers are now trying to utilize oral microbiota in cancer diagnosis and treatment. 

oral squamous cell carcinoma oral microbiome

1. Introduction

More than 90% of oral cancers, which rank 16th among all the common malignant tumors, are oral squamous cell carcinomas (OSCCs) originating from the squamous tissues [1]. Advances in medical imaging and therapy have improved the 5-year overall survival from 59% during 1990–2000 to 70% during 2001–2010 [2]; however, there were 377,713 cases of oral and lip cancer and 177,757 deaths in 2020 [3]. The etiology of OSCC is attributed to genetics; microbes; and unhealthy habits, including alcoholism [4], smoking [5], and chewing betel [6]. Periodontal diseases and tooth loss are also risk factors for OSCC [7][8], indicating that several oral bacteria (Streptococcus, Peptostreptococcus, and Prevotella) may be related to the development of OSCC [9]. Microorganisms that colonize the human body were found to be associated with 20% of cancers and are known to modulate tumor occurrence and development since Helicobacter pylori (H. Pylori) was found to contribute to gastric cancer in the 1990s [10]. The number of bacteria is almost equal to that of human cells in the body, and these microorganisms have at least 100 times more metagenomes than humans, which can be utilized to modulate the biological behavior of cancer cells [11] by promoting cell proliferation, resisting cell death, inducing angiogenesis, reprogramming energy metabolism, and evading immune destruction [12]. Increasing evidence suggests that microorganisms play a significant role in oral cancer development. Therefore, the mechanisms of microbial carcinogenesis should be explored, and a cure must be developed for oral cancer.

2. Clinical Application of Oral Microbes in Oral Squamous Cell Carcinoma

2.1. Diagnosis and Grading

Several advanced approaches can detect oral cancer, such as lab-on-chip, microfluidics, nanodiagnostics, liquid biopsy, omics technology, and synthetic biology [13]. To date, numerous studies have applied different methods to describe the differences in oral microbiota between normal tissue and OSCC sites [14][15][16][17], including the surface of the tumor tissue, within the tumor, and saliva. Allan Radaic etc. made an exhaustive summary of potential oral microbiome-based biomarkers for OSCC [18]. It is possible to distinguish cancerous lesions from normal tissues and perform tumor staging by noninvasively detecting microbes [19].
Intratumoral bacteria potentially originate from normal adjacent tissues [20] and play the role of immunomodulation in the tumor microenvironment [21]. Hooper et al. were the first to study microorganisms in OSCC and suggested that they are mainly aciduric and saccharolytic secondary colonizers, such as Micrococcus luteus, Prevotella melaninogenica, Exiguobacterium oxidotolerans, and Staphylococcus aureus, because of their acidic and hypoxic environments [22]. The abundances of the phylum Fusobacteria, genus Fusobacterium, and phylum Bacteroidetes were found to be elevated in the saliva of patients with OSCC and were believed to be diagnostically specific [23]. Aside from viruses and bacteria, a variety of molecular and genetic markers can be detected for treatment and monitoring [24]. A recent study reported that oral-cancer-related microorganisms in the mucosa, other than in gingival plaque or saliva samples, have the most diverse species differences and functional changes and are the most suitable sites for observing microbial dysregulation [25]. Another study that investigated unstimulated salivary microbial profiles found significant differences in Bacillus, Enterococcus, Parvimonas, Peptostreptococcus, and Slackia between epithelial precursor lesions and cancer groups [26]. As early as 2005, Madhura et al. found that with Capnocytophaga gingivalis, Prevotella melaninogenica, and Streptococcus mitis as diagnostic markers, the sensitivity and specificity for the three species are 80% and 82%, respectively [27]. Zhou et al. adopted random forests and cross-validations to build a diagnostic model based on oral microbiota and found that Actinobacteria, Fusobacterium, Moraxella, Bacillus, and Veillonella species were strongly correlated with OSCC [28]. However, Parvimonas micra and Streptococcus mitis have been implicated in the reduced risk of OSCC development [29][30][31][32]. The presence of Corynebacterium and Kingella is also associated with a low incidence of head and neck squamous cell carcinoma, possibly because they are involved in the degradation of cancer-inducing metabolites [29][33]. Similarly, Shen et al. found that periodontitis-negative-associated bacteria (Neisseria sicca and Corynebacterium matruchotii) play an anti-cancer role in OSCC by upregulating DDR to repair DNA damage, inducing pyroptosis, and decreasing CD4+ T cells [34]. P. gingivalis IgG and IL-6 are also used as potential serum biomarkers for OSCC diagnosis [35]. As the expression patterns of CXCL10, DIAPH1, NCLN, and MMP9 genes are significantly correlated with interpain A, fadA, and bspA in OSCC cases, gene expression is an alternative target to detect OSCC [36].
With the progression of OSCC, the abundance of these bacteria increases, indicating that the microbiome can serve as a marker for staging and predicting prognosis. Yang et al. reported that F. periodonticum, S. mitis, and P. pasteri are bacterial marker panels that can be used to distinguish patients with stage 4 OSCC from healthy individuals [37]. Tumor MMP-9 expression is associated with poor outcomes in OPSCC, especially in HPV-negative disease, whereas Rgp immunoexpression in inflammatory cells is associated with better disease-specific survival, which can be utilized to predict prognosis [38].
In addition to diagnosing the disease, microorganisms can also be used to distinguish healthy from diseased mucosa. Su et al. demonstrated that Fusobacterium spp. is a successful marker species for identifying noncancerous tissues. However, compared with Fusobacterium spp., Streptococcus spp., especially Streptococcus pneumoniae, are more accurate when classifying lesion sites [16].

2.2. Oral Microbes and Cancer Treatment

Multidisciplinary therapeutic strategies are generally used for OPMDs to prevent OSCC progression and prolong survival. However, there is no consensus on the treatment of OPMDs owing to the variety and complex mechanisms of OPMDs. Tacrolimus, which is used as the first-line drug after transplantation, was found to be effective in treating OLP [39][40] by downregulating immunity [41] and downregulating cell-cycle-related proteins [42]. Tacrolimus treatment also significantly altered the proportion of Allobaculum, Bacteroides, and Lactobacillus in the colonic mucosa and the circulation [43], which indicated that it may improve microbial dysregulation of mucosal surfaces. Some studies reported that tacrolimus promotes tumorigenesis and leads to adverse events [44][45], while others have reached a different conclusion [46][47][48]. Topical tacrolimus can be an effective second-line therapy for patients who do not respond to corticosteroids. However, further studies on its adverse effects are required.
A combination of surgery, chemotherapy, and radiotherapy has been administered to patients with OSCC. Recently, more attention has been paid to the oral microbiome, as the structural, metabolic, and virulence characteristics of microbes are potential targets. The use of pre- or probiotics and salivary substitutes was also suggested based on differences in the salivary microbiota between patients with OSCC and healthy controls [49][50]. The concept of oncolytic bacterial immunotherapy has long been popular, as commonly used radiotherapy and chemotherapy have side effects owing to damage to healthy tissues, while microorganism therapy shows the merits of accurate target specificity, tissue penetration, and less treatment expense. Many engineered bacterial strains were generated to overcome potential safety problems and improve tumor targeting [51]. Salmonella typhimurium [52], Escherichia coli [53], and Bifidobacterium [54] showed outstanding anti-cancer activities in both preclinical and clinical trials. Bifidobacterium, Streptococcus, Caulobacter, and Clostridium spp. are commonly found in the oral cavity and are promising candidates for OSCC tumor-targeting therapies [55]. Oncolytic or “cancer-killing” viruses have been highly used as immunotherapeutic drugs for the treatment of cancer as well [56] and are combined with radiotherapy, chemotherapy drugs, or other strategies. Nonetheless, concerns remain regarding the use of microorganisms in tumor therapies. Owing to the weakened immune system, bacteria-mediated tumor therapy is ineffective in patients who have undergone chemotherapy [57] and can cause serious infections. Moreover, bacterial monotherapy does not completely cure cancer, and bacterium-mediated synergistic cancer therapy was proposed to have promising potential [58][59]. Further studies are warranted to understand the interactions between oncolytic immunotherapies and other therapies.

2.3. Microbiota and Treatment Outcomes of Oral Squamous Cell Carcinoma

Increasing evidence indicates that the presence of a microbiome can affect treatment outcomes [60]. Recent research found an increase in Lactobacillaceae and Bifidobacteriaceae families and a decrease in Porphyromonadaceae and Prevotellaceae after OSCC treatment. Furthermore, they observed a change in DMBT1 expression accompanied by the microbiome change, suggesting DMBT1 to be a possible treatment indicator [61]. And a certain genus, namely, Leptotrichia, was shown to improve patient prognosis [62]. Another prediction model with five microbial signatures, namely, Leptotrichia trevisanii, Capnocytophaga sputigena, Capnocytophaga, Cardiobacterium, and Olsenella, displayed high accuracy [63]. Cancer-related intratumoral bacteria and gut microbiota influence the effectiveness of chemotherapy. Lehouritis et al. found that bacteria can both decrease or increase the effectiveness of chemotherapeutic drugs via enzymatic biotransformation and chemical modification [64]. In a mouse model of colon cancer, intratumor Gammaproteobacteria converted gemcitabine into its inactive form by expressing the bacterial enzyme cytidine deaminase [65]. Another study found that 5-FU is metabolized by preTA-encoding bacteria [66]. Microbes modulate drug toxicity and side effects. In mice raised in a germ-free environment and administered antibiotic prophylaxis, oxyaliplatin-induced mechanical hyperalgesia was reduced, indicating that the gut microbiota enhanced chemotherapy-induced mechanical hyperalgesia [67]. Simultaneously, because microorganisms have a regulatory effect on immune-inflammatory responses, they also affect immunotherapy. Fusobacteria species are associated with the high expression of IL-12 and TGF-β, ultimately promoting the differentiation of T cells [68]. As for radiotherapy, antibiotic-mediated fungal reduction enhances the response to radiation, whereas antibiotic-mediated bacterial reduction presents the opposite results [69]. Significant microbiome changes can also affect radiation-induced osteoradionecrosis [70]. Current research on the microbial effects of cancer therapy mainly focuses on digestive tract cancers, requiring further exploration for oral cancer. Although the mechanism by which these microbes affect the efficacy of anti-cancer treatments remains unclear, a growing number of studies have shown that microbes are inextricably linked to anti-cancer treatments.
In addition to regulating cancer treatment, the microbiome can also be a target for regulating immune-related adverse events and even the prognosis of cancer treatment, as cancer treatments can lead to microflora dysregulation. Almost 75% of patients with head and neck cancer who undergo chemotherapy or radiotherapy treatment experience oral mucositis (OM) [71]. After receiving a 5-fluorouracil (5-FU) i.v. for 6 d, an increase in facultative and strictly anaerobic bacteria in the oral cavity and facultative anaerobes in the colon is observed [72]. Hong et al. also demonstrated that OM severity is associated with 5-FU [73]. Modification of oral microbiome is a promising preventive treatment for OM [74][75]. Palifermin, which is the only pharmacological agent approved by the FDA to treat OM, is a recombinant human keratinocyte growth factor (KGF) that targets the KGF receptor to enhance the differentiation and maturation of epithelial cells [71][76]. A recent meta-analysis showed that palifermin reduces the incidence of severe mucositis by up to 30% in patients treated with chemotherapy and radiotherapy [77]. Therefore, palifermin can be used as a prophylactic to prevent severe OM in patients with oral cancer. Recent research found that palifermin affects the oral microbial community composition, though more studies are warranted to figure out the correlations between palifermin and community composition changes [78]. However, in the 2021 European clinical practice guidelines, palifermin is not recommended for pediatric patients receiving cancer treatment [79] because of its short-term adverse effects, potential long-term negative effects on cancer outcomes, high costs, and restricted availability. Palifermin can be used as a prophylactic to prevent severe OM in patients with oral cancer; more reliable evidence is needed on the safety and efficacy of palifermin. Interestingly, Lactococcus strains were shown to be effective in the control of 5-FU-dysbiosis [80], indicating that probiotic supplementation may be a prophylaxis to reduce the adverse effects of cancer therapies and improve the quality of patients’ lives. Table 1 summarizes the promising clinical applications of oral microbes in OSCC.
Table 1. Summary of the role of microorganisms in the diagnosis, treatment, and prognosis of cancer.
Diagnosis and prognosis predicting markers Capnocytophaga gingivalis, Prevotella melaninogenica, and Streptococcus mitis [27]
P. gingivalis IgG and IL-6 [35]
CXCL10, DIAPH1, NCLN, and MMP9 genes [36]
F. periodonticum, S. mitis, and P. pasteri [37]
Fusobacterium periodonticum, Parvimonas micra, Streptococcus constellatus, Haemophilus influenza, and Filifactor alocis [37]
Leptotrichia [62][63]
Tumoral MMP-9 [38]
Treatment targets Tacrolimus [39][40]
Bifidobacterium, Streptococcus, Caulobacter, and Clostridium spp. [55]
Affecting treatment outcome Gammaproteobacteria convert gemcitabine into its inactive form by expressing the bacterial enzyme cytidine deaminase [65]
preTA-encoding bacteria metabolizes 5-FU [66]
Gut microbiota enhances chemotherapy-induced mechanical hyperalgesia [67]
Fusobacteria species promote the differentiation of T cells [68]
Antibiotic-mediated fungal reduction enhances the response to radiation and antibiotic-mediated bacteria reduction presents the opposite results [69]
Palifermin [77]
Lactococci strains relieve OM caused by 5-FU [80]


  1. Warnakulasuriya, S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009, 45, 309–316.
  2. Amit, M.; Yen, T.C.; Liao, C.T.; Chaturvedi, P.; Agarwal, J.P.; Kowalski, L.P.; Ebrahimi, A.; Clark, J.R.; Kreppel, M.; Zöller, J.; et al. Improvement in survival of patients with oral cavity squamous cell carcinoma: An international collaborative study. Cancer 2013, 119, 4242–4248.
  3. Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021, 71, 209–249.
  4. Hoes, L.; Dok, R.; Verstrepen, K.J.; Nuyts, S. Ethanol-Induced Cell Damage Can Result in the Development of Oral Tumors. Cancers 2021, 13, 3846.
  5. Ford, P.J.; Rich, A.M. Tobacco Use and Oral Health. Addiction 2021, 116, 3531–3540.
  6. Wang, W.-C.; Chiu, Y.-T.; Wang, Y.-Y.; Lu, S.-L.; Chan, L.-P.; Lee, C.-Y.; Yang, F.M.; Yuan, S.F.; Lee, C.-H. Effects of DSM-5 Betel-Quid-Related Symptoms, Pathological Behaviors, and Use Disorder on Oral Squamous Cell Carcinoma Risk. Cancers 2022, 14, 3974.
  7. Healy, C.M.; Moran, G.P. The microbiome and oral cancer: More questions than answers. Oral Oncol. 2019, 89, 30–33.
  8. Ganly, I.; Yang, L.; Giese, R.A.; Hao, Y.; Nossa, C.W.; Morris, L.G.; Rosenthal, M.; Migliacci, J.; Kelly, D.; Tseng, W.; et al. Periodontal pathogens are a risk factor of oral cavity squamous cell carcinoma, independent of tobacco and alcohol and human papillomavirus. Int. J. Cancer 2019, 145, 775–784.
  9. Karpiński, T.M. Role of Oral Microbiota in Cancer Development. Microorganisms 2019, 7, 20.
  10. Yao, X.; Smolka, A.J. Gastric Parietal Cell Physiology and Helicobacter pylori–Induced Disease. Gastroenterology 2019, 156, 2158–2173.
  11. Tierney, B.T.; Yang, Z.; Luber, J.M.; Beaudin, M.; Wibowo, M.C.; Baek, C.; Mehlenbacher, E.; Patel, C.J.; Kostic, A.D. The Landscape of Genetic Content in the Gut and Oral Human Microbiome. Cell Host Microbe 2019, 26, 283–295.
  12. Stasiewicz, M.; Karpiński, T.M. The oral microbiota and its role in carcinogenesis. Semin. Cancer Biol. 2022, 86 Pt 3, 633–642.
  13. Madhura, M.G.; Rao, R.S.; Patil, S.; Fageeh, H.N.; Alhazmi, A.; Awan, K.H. Advanced diagnostic aids for oral cancer. Disease-a-Month 2020, 66, 101034.
  14. Li, Z.; Liu, Y.; Zhang, L. Role of the microbiome in oral cancer occurrence, progression and therapy. Microb. Pathog. 2022, 169, 105638.
  15. Frank, D.N.; Qiu, Y.; Cao, Y.; Zhang, S.; Lu, L.; Kofonow, J.M.; Robertson, C.E.; Liu, Y.; Wang, H.; Levens, C.L.; et al. A dysbiotic microbiome promotes head and neck squamous cell carcinoma. Oncogene 2022, 41, 1269–1280.
  16. Su, S.-C.; Chang, L.-C.; Huang, H.-D.; Peng, C.-Y.; Chuang, C.-Y.; Chen, Y.-T.; Lu, M.-Y.; Chiu, Y.-W.; Chen, P.-Y.; Yang, S.-F. Oral microbial dysbiosis and its performance in predicting oral cancer. Carcinogenesis 2021, 42, 127–135.
  17. Arthur, R.A.; Dos Santos Bezerra, R.; Ximenez, J.P.B.; Merlin, B.L.; de Andrade Morraye, R.; Neto, J.V.; Fava, N.M.N.; Figueiredo, D.L.A.; de Biagi, C.A.O., Jr.; Montibeller, M.J.; et al. Microbiome and oral squamous cell carcinoma: A possible interplay on iron metabolism and its impact on tumor microenvironment. Braz. J. Microbiol. 2021, 52, 1287–1302.
  18. Radaic, A.; Kamarajan, P.; Cho, A.; Wang, S.; Hung, G.-C.; Najarzadegan, F.; Wong, D.T.; Ton-That, H.; Wang, C.-Y.; Kapila, Y.L. Biological biomarkers of oral cancer. Periodontology 2000 2023.
  19. Wang, S.; Yang, M.; Li, R.; Bai, J. Current advances in noninvasive methods for the diagnosis of oral squamous cell carcinoma: A review. Eur. J. Med. Res. 2023, 28, 53.
  20. Nejman, D.; Livyatan, I.; Fuks, G.; Gavert, N.; Zwang, Y.; Geller, L.T.; Rotter-Maskowitz, A.; Weiser, R.; Mallel, G.; Gigi, E.; et al. The human tumor microbiome is composed of tumor type–specific intracellular bacteria. Science 2020, 368, 973–980.
  21. Singh, R.P.; Kumari, N.; Gupta, S.; Jaiswal, R.; Mehrotra, D.; Singh, S.; Mukherjee, S.; Kumar, R. Intratumoral Microbiota Changes with Tumor Stage and Influences the Immune Signature of Oral Squamous Cell Carcinoma. Microbiol. Spectr. 2023, 11, e0459622.
  22. Hooper, S.J.; Crean, S.J.; Lewis, M.A.O.; Spratt, D.A.; Wade, W.G.; Wilson, M.J. Viable Bacteria Present within Oral Squamous Cell Carcinoma Tissue. J. Clin. Microbiol. 2006, 44, 1719–1725.
  23. Hashimoto, K.; Shimizu, D.; Ueda, S.; Miyabe, S.; Oh-Iwa, I.; Nagao, T.; Shimozato, K.; Nomoto, S. Feasibility of oral microbiome profiles associated with oral squamous cell carcinoma. J. Oral Microbiol. 2022, 14, 2105574.
  24. Kumar, P.; Gupta, S.; Das, B.C. Saliva as a potential non-invasive liquid biopsy for early and easy diagnosis/prognosis of head and neck cancer. Transl. Oncol. 2023, 40, 101827.
  25. Heng, W.; Wang, W.; Dai, T.; Jiang, P.; Lu, Y.; Li, R.; Zhang, M.; Xie, R.; Zhou, Y.; Zhao, M.; et al. Oral Bacteriome and Mycobiome across Stages of Oral Carcinogenesis. Microbiol. Spectr. 2022, 10, e0273722.
  26. Lee, W.-H.; Chen, H.-M.; Yang, S.-F.; Liang, C.; Peng, C.-Y.; Lin, F.-M.; Tsai, L.-L.; Wu, B.-C.; Hsin, C.-H.; Chuang, C.-Y.; et al. Bacterial alterations in salivary microbiota and their association in oral cancer. Sci. Rep. 2017, 7, 16540.
  27. Mager, D.L.; Haffajee, A.D.; Devlin, P.M.; Norris, C.M.; Posner, M.R.; Goodson, J.M. The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive, non-randomized study of cancer-free and oral squamous cell carcinoma subjects. J. Transl. Med. 2005, 3, 27.
  28. Zhou, X.; Hao, Y.; Peng, X.; Li, B.; Han, Q.; Ren, B.; Li, M.; Li, L.; Li, Y.; Cheng, G.; et al. The Clinical Potential of Oral Microbiota as a Screening Tool for Oral Squamous Cell Carcinomas. Front. Cell. Infect. Microbiol. 2021, 11, 728933.
  29. Hayes, R.B.; Ahn, J.; Fan, X.; Peters, B.A.; Ma, Y.; Yang, L.; Agalliu, I.; Burk, R.D.; Ganly, I.; Purdue, M.P.; et al. Association of Oral Microbiome with Risk for Incident Head and Neck Squamous Cell Cancer. JAMA Oncol. 2018, 4, 358–365.
  30. Schmidt, B.L.; Kuczynski, J.; Bhattacharya, A.; Huey, B.; Corby, P.M.; Queiroz, E.L.S.; Nightingale, K.; Kerr, A.R.; DeLacure, M.D.; Veeramachaneni, R.; et al. Changes in Abundance of Oral Microbiota Associated with Oral Cancer. PLoS ONE 2014, 9, e98741.
  31. Al-Hebshi, N.N.; Nasher, A.T.; Maryoud, M.Y.; Homeida, H.E.; Chen, T.; Idris, A.M.; Johnson, N.W. Inflammatory bacteriome featuring Fusobacterium nucleatum and Pseudomonas aeruginosa identified in association with oral squamous cell carcinoma. Sci. Rep. 2017, 7, 1834.
  32. Zhao, Q.; Yang, T.; Yan, Y.; Zhang, Y.; Li, Z.; Wang, Y.; Yang, J.; Xia, Y.; Xiao, H.; Han, H.; et al. Alterations of Oral Microbiota in Chinese Patients with Esophageal Cancer. Front. Cell. Infect. Microbiol. 2020, 10, 541144.
  33. Peng, Q.-S.; Cheng, Y.-N.; Zhang, W.-B.; Fan, H.; Mao, Q.-H.; Xu, P. circRNA_0000140 suppresses oral squamous cell carcinoma growth and metastasis by targeting miR-31 to inhibit Hippo signaling pathway. Cell Death Dis. 2020, 11, 112.
  34. Shen, X.; Zhang, B.; Hu, X.; Li, J.; Wu, M.; Yan, C.; Yang, Y.; Li, Y. Neisseria sicca and Corynebacterium matruchotii inhibited oral squamous cell carcinomas by regulating genome stability. Bioengineered 2022, 13, 14094–14106.
  35. Park, D.-G.; Woo, B.H.; Lee, B.-J.; Yoon, S.; Cho, Y.; Kim, Y.-D.; Park, H.R.; Song, J.M. Serum Levels of Interleukin-6 and Titers of Antibodies against Porphyromonas gingivalis Could Be Potential Biomarkers for the Diagnosis of Oral Squamous Cell Carcinoma. Int. J. Mol. Sci. 2019, 20, 2749.
  36. Moghimi, M.; Bakhtiari, R.; Mehrabadi, J.F.; Jamshidi, N.; Jamshidi, N.; Siyadatpanah, A.; Mitsuwan, W.; Nissapatorn, V. Interaction of human oral cancer and the expression of virulence genes of dental pathogenic bacteria. Microb. Pathog. 2020, 149, 104464.
  37. Yang, C.-Y.; Yeh, Y.-M.; Yu, H.-Y.; Chin, C.-Y.; Hsu, C.-W.; Liu, H.; Huang, P.-J.; Hu, S.-N.; Liao, C.-T.; Chang, K.-P.; et al. Oral Microbiota Community Dynamics Associated with Oral Squamous Cell Carcinoma Staging. Front. Microbiol. 2018, 9, 862.
  38. Kylmä, A.K.; Sorsa, T.; Jouhi, L.; Mustonen, H.K.; Mohamed, H.; Randén-Brady, R.; Mäkitie, A.; Atula, T.; Hagström, J.; Haglund, C. Prognostic Role of Porphyromonas gingivalis Gingipain Rgp and Matrix Metalloproteinase 9 in Oropharyngeal Squamous Cell Carcinoma. Anticancer Res. 2022, 42, 5415–5430.
  39. Utz, S.; Suter, V.G.A.; Cazzaniga, S.; Borradori, L.; Feldmeyer, L. Outcome and long-term treatment protocol for topical tacrolimus in oral lichen planus. J. Eur. Acad. Dermatol. Venereol. 2022, 36, 2459–2465.
  40. Polizzi, A.; Santonocito, S.; Lo Giudice, A.; Alibrandi, A.; De Pasquale, R.; Isola, G. Analysis of the response to two pharmacological protocols in patients with oral lichen planus: A randomized clinical trial. Oral Dis. 2023, 29, 755–763.
  41. Mok, C.C.; Tong, K.H.; To, C.H.; Siu, Y.P.; Au, T.C. Tacrolimus for induction therapy of diffuse proliferative lupus nephritis: An open-labeled pilot study. Kidney Int. 2005, 68, 813–817.
  42. Li, Y.; Wang, Y.; Li, J.; Ling, Z.; Chen, W.; Zhang, L.; Hu, Q.; Wu, T.; Cheng, B.; Wang, Y.; et al. Tacrolimus inhibits oral carcinogenesis through cell cycle control. Biomed. Pharmacother. 2021, 139, 111545.
  43. Zhang, Z.; Liu, L.; Tang, H.; Jiao, W.; Zeng, S.; Xu, Y.; Zhang, Q.; Sun, Z.; Mukherjee, A.; Zhang, X.; et al. Immunosuppressive effect of the gut microbiome altered by high-dose tacrolimus in mice. Am. J. Transplant. 2018, 18, 1646–1656.
  44. Sun, S.L.; Liu, J.J.; Zhong, B.; Wang, J.K.; Jin, X.; Xu, H.; Yin, F.Y.; Liu, T.N.; Chen, Q.M.; Zeng, X. Topical calcineurin inhibitors in the treatment of oral lichen planus: A systematic review and meta-analysis. Br. J. Dermatol. 2019, 181, 1166–1176.
  45. Cheng, J.Y.; Li, F.-Y.; Ko, C.J.; Colegio, O.R. Cutaneous Squamous Cell Carcinomas in Solid Organ Transplant Recipients Compared with Immunocompetent Patients. JAMA Dermatol. 2018, 154, 60–66.
  46. Zaalberg, A.; Tuchayi, S.M.; Ameri, A.H.; Ngo, K.H.; Cunningham, T.J.; Eliane, J.-P.; Livneh, M.; Horn, T.D.; Rosman, I.S.; Musiek, A.; et al. Chronic Inflammation Promotes Skin Carcinogenesis in Cancer-Prone Discoid Lupus Erythematosus. J. Investig. Dermatol. 2019, 139, 62–70.
  47. Veitch, M.; Beaumont, K.; Pouwer, R.; Chew, H.Y.; Frazer, I.H.; Soyer, H.P.; Campbell, S.; Dymock, B.W.; Harvey, A.; Cock, T.-A.; et al. Local blockade of tacrolimus promotes T-cell-mediated tumor regression in systemically immunosuppressed hosts. J. Immunother. Cancer 2023, 11, e006783.
  48. Su, Z.; Hu, J.; Cheng, B.; Tao, X. Efficacy and safety of topical administration of tacrolimus in oral lichen planus: An updated systematic review and meta-analysis of randomized controlled trials. J. Oral Pathol. Med. Off. Publ. Int. Assoc. Oral Pathol. Am. Acad. Oral Pathol. 2022, 51, 63–73.
  49. Mäkinen, A.I.; Pappalardo, V.Y.; Buijs, M.J.; Brandt, B.W.; Mäkitie, A.A.; Meurman, J.H.; Zaura, E. Salivary microbiome profiles of oral cancer patients analyzed before and after treatment. Microbiome 2023, 11, 171.
  50. Diwan, P.; Nirwan, M.; Bahuguna, M.; Kumari, S.P.; Wahlang, J.; Gupta, R.K. Evaluating Alterations of the Oral Microbiome and Its Link to Oral Cancer among Betel Quid Chewers: Prospecting Reversal through Probiotic Intervention. Pathogens 2023, 12, 996.
  51. Zhou, S.; Gravekamp, C.; Bermudes, D.; Liu, K. Tumour-targeting bacteria engineered to fight cancer. Nat. Rev. Cancer 2018, 18, 727–743.
  52. Xiong, S.; Qi, Z.; Ni, J.; Zhong, J.; Cao, L.; Yang, K. Attenuated Salmonella typhimurium-mediated tumour targeting imaging based on peptides. Biomater. Sci. 2020, 8, 3712–3719.
  53. Yu, X.; Lin, C.; Yu, J.; Qi, Q.; Wang, Q. Bioengineered Escherichia coli Nissle 1917 for tumour-targeting therapy. Microb. Biotechnol. 2020, 13, 629–636.
  54. Li, Q.; Li, Y.; Wang, Y.; Xu, L.; Guo, Y.; Wang, Y.; Wang, L.; Guo, C. Oral administration of Bifidobacterium breve promotes antitumor efficacy via dendritic cells-derived interleukin 12. OncoImmunology 2021, 10, 1868122.
  55. Liu, S.; Xu, X.; Zeng, X.; Li, L.; Chen, Q.; Li, J. Tumor-targeting bacterial therapy: A potential treatment for oral cancer (Review). Oncol. Lett. 2014, 8, 2359–2366.
  56. Wedge, M.-E.; Jennings, V.A.; Crupi, M.J.F.; Poutou, J.; Jamieson, T.; Pelin, A.; Pugliese, G.; de Souza, C.T.; Petryk, J.; Laight, B.J.; et al. Virally programmed extracellular vesicles sensitize cancer cells to oncolytic virus and small molecule therapy. Nat. Commun. 2022, 13, 1898.
  57. Dróżdż, M.; Makuch, S.; Cieniuch, G.; Woźniak, M.; Ziółkowski, P. Obligate and facultative anaerobic bacteria in targeted cancer therapy: Current strategies and clinical applications. Life Sci. 2020, 261, 118296.
  58. Guo, Y.; Song, M.; Liu, X.; Chen, Y.; Xun, Z.; Sun, Y.; Tan, W.; He, J.; Zheng, J.H. Photodynamic therapy-improved oncolytic bacterial immunotherapy with FAP-encoding S. typhimurium. J. Control. Release 2022, 351, 860–871.
  59. Lou, X.; Chen, Z.; He, Z.; Sun, M.; Sun, J. Bacteria-Mediated Synergistic Cancer Therapy: Small Microbiome Has a Big Hope. Nano-Micro Lett. 2021, 13, 37.
  60. Panebianco, C.; Andriulli, A.; Pazienza, V. Pharmacomicrobiomics: Exploiting the drug-microbiota interactions in anticancer therapies. Microbiome 2018, 6, 92.
  61. Medeiros, M.C.; The, S.; Bellile, E.; Russo, N.; Schmitd, L.; Danella, E.; Singh, P.; Banerjee, R.; Bassis, C.; Murphy, G.R., 3rd; et al. Salivary microbiome changes distinguish response to chemoradiotherapy in patients with oral cancer. Microbiome 2023, 11, 268.
  62. Hamada, M.; Inaba, H.; Nishiyama, K.; Yoshida, S.; Yura, Y.; Matsumoto-Nakano, M.; Uzawa, N. Potential Role of the Intratumoral Microbiota in Prognosis of Head and Neck Cancer. Int. J. Mol. Sci. 2023, 24, 15456.
  63. Lyu, W.-N.; Lin, M.-C.; Shen, C.-Y.; Chen, L.-H.; Lee, Y.-H.; Chen, S.-K.; Lai, L.-C.; Chuang, E.Y.; Lou, P.-J.; Tsai, M.-H. An Oral Microbial Biomarker for Early Detection of Recurrence of Oral Squamous Cell Carcinoma. ACS Infect. Dis. 2023, 9, 1783–1792.
  64. Lehouritis, P.; Cummins, J.; Stanton, M.; Murphy, C.T.; McCarthy, F.O.; Reid, G.; Urbaniak, C.; Byrne, W.L.; Tangney, M. Local bacteria affect the efficacy of chemotherapeutic drugs. Sci. Rep. 2015, 5, 14554.
  65. Geller, L.T.; Barzily-Rokni, M.; Danino, T.; Jonas, O.H.; Shental, N.; Nejman, D.; Gavert, N.; Zwang, Y.; Cooper, Z.A.; Shee, K.; et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science 2017, 357, 1156–1160.
  66. Spanogiannopoulos, P.; Kyaw, T.S.; Guthrie, B.G.H.; Bradley, P.H.; Lee, J.V.; Melamed, J.; Malig, Y.N.A.; Lam, K.N.; Gempis, D.; Sandy, M.; et al. Host and gut bacteria share metabolic pathways for anti-cancer drug metabolism. Nat. Microbiol. 2022, 7, 1605–1620.
  67. Shen, S.; Lim, G.; You, Z.; Ding, W.; Huang, P.; Ran, C.; Doheny, J.; Caravan, P.; Tate, S.; Hu, K.; et al. Gut microbiota is critical for the induction of chemotherapy-induced pain. Nat. Neurosci. 2017, 20, 1213–1216.
  68. Cremonesi, E.; Governa, V.; Garzon, J.F.G.; Mele, V.; Amicarella, F.; Muraro, M.G.; Trella, E.; Galati-Fournier, V.; Oertli, D.; Däster, S.R.; et al. Gut microbiota modulate T cell trafficking into human colorectal cancer. Gut 2018, 67, 1984–1994.
  69. Shiao, S.L.; Kershaw, K.M.; Limon, J.J.; You, S.; Yoon, J.; Ko, E.Y.; Guarnerio, J.; Potdar, A.A.; McGovern, D.P.B.; Bose, S.; et al. Commensal bacteria and fungi differentially regulate tumor responses to radiation therapy. Cancer Cell 2021, 39, 1202–1213.
  70. Li, Z.; Fu, R.; Huang, X.; Wen, X.; Zhang, L. Oral microbiota may affect osteoradionecrosis following radiotherapy for head and neck cancer. J. Transl. Med. 2023, 21, 391.
  71. McDonnell, A.M.; Lenz, K.L. Palifermin: Role in the Prevention of Chemotherapy- and Radiation-Induced Mucositis. Ann. Pharmacother. 2007, 41, 86–94.
  72. von Bültzingslöwen, I.; Adlerberth, I.; Wold, A.E.; Dahlén, G.; Jontell, M. Oral and intestinal microflora in 5-fluorouracil treated rats, translocation to cervical and mesenteric lymph nodes and effects of probiotic bacteria. Oral Microbiol. Immunol. 2003, 18, 278–284.
  73. Hong, B.-Y.; Sobue, T.; Choquette, L.; Dupuy, A.K.; Thompson, A.; Burleson, J.A.; Salner, A.L.; Schauer, P.K.; Joshi, P.; Fox, E.; et al. Chemotherapy-induced oral mucositis is associated with detrimental bacterial dysbiosis. Microbiome 2019, 7, 66.
  74. Fernández Forné, Á.; García Anaya, M.J.; Segado Guillot, S.J.; Plaza Andrade, I.; de la Peña Fernández, L.; Lorca Ocón, M.J.; Lupiáñez Pérez, Y.; Queipo-Ortuño, M.I.; Gómez-Millán, J. Influence of the microbiome on radiotherapy-induced oral mucositis and its management: A comprehensive review. Oral Oncol. 2023, 144, 106488.
  75. Fallah, M.; Amin, N.; Moghaddasian, M.H.; Jafarnejad, S. Probiotics for the Management of Oral Mucositis: An Interpretive Review of Current Evidence. Adv. Pharm. Bull. 2023, 13, 269–274.
  76. Vadhan-Raj, S.; Goldberg, J.D.; Perales, M.A.; Berger, D.P.; van den Brink, M.R. Clinical applications of palifermin: Amelioration of oral mucositis and other potential indications. J. Cell. Mol. Med. 2013, 17, 1371–1384.
  77. Coutsouvelis, J.; Corallo, C.; Spencer, A.; Avery, S.; Dooley, M.; Kirkpatrick, C.M. A meta-analysis of palifermin efficacy for the management of oral mucositis in patients with solid tumours and haematological malignancy. Crit. Rev. Oncol. Hematol. 2022, 172, 103606.
  78. Bohn, B.; Chalupova, M.; Staley, C.; Holtan, S.; Maakaron, J.; Bachanova, V.; El Jurdi, N. Temporal variation in oral microbiome composition of patients undergoing autologous hematopoietic cell transplantation with keratinocyte growth factor. BMC Microbiol. 2023, 23, 258.
  79. Patel, P.; Robinson, P.D.; Baggott, C.; Gibson, P.; Ljungman, G.; Massey, N.; Ottaviani, G.; Phillips, R.; Revon-Rivière, G.; Treister, N.; et al. Clinical practice guideline for the prevention of oral and oropharyngeal mucositis in pediatric cancer and hematopoietic stem cell transplant patients: 2021 update. Eur. J. Cancer 2021, 154, 92–101.
  80. Carvalho, R.; Vaz, A.; Pereira, F.L.; Dorella, F.; Aguiar, E.; Chatel, J.-M.; Bermudez, L.; Langella, P.; Fernandes, G.; Figueiredo, H.; et al. Gut microbiome modulation during treatment of mucositis with the dairy bacterium Lactococcus lactis and recombinant strain secreting human antimicrobial PAP. Sci. Rep. 2018, 8, 15072.
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