DOI:

10.37988/1811-153X_2026_2_54

Endogenous factors contributing to the development of potentially malignant diseases and malignant nodules of the oral mucous membrane (systematic review)

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Authors

  • G.S. Mezhevikina 1, PhD in Medical Sciences, associate professor of the Therapeutic and pediatric dentistry Department
    ORCID: 0000-0001-7937-3501
  • V.D. Vagner 1, 2, Doctor of Science in Medicine, professor of the Therapeutic and pediatric dentistry Department; professor of the Oral mucous membrane diseases and geriatric dentistry Department
    ORCID: 0000-0002-9136-9289
  • M.Ya. Abramova 2, Doctor of Science in Medicine, full professor of the Oral mucous membrane diseases and geriatric dentistry Department
    ORCID: 0000-0001-7762-1540
  • S.I. Cherkesova 1, PhD in Medical Sciences, associate professor and head of the Therapeutic and pediatric dentistry Department
    ORCID: 0000-0001-5814-4689
  • 1 Ryazan State Medical University, 390026, Ryazan, Russia
  • 2 Russian University of Medicine, 127006, Moscow, Russia

Abstract

Malignant neoplasms (MNs) remain a problem of high socioeconomic significance. Currently, there is a steady increase in the incidence of MNs worldwide, which requires a thorough study of the factors predisposing to the development of potentially malignant diseases (PMDs) and MNs of the oral mucosa (OM). The purpose of this study is to analyze the results of research conducted by Russian and foreign scientists on the influence of endogenous factors on the development of PMDs and MNs of the OM, based on current literature data, and to outline prospects for future research.
Materials and methods.
During 2025, a search for modern scientific publications was carried out using the Russian electronic library eLibrary, the international system PubMed, the resource “CyberLeninka”. After careful selection for compliance with the inclusion criteria and subject matter, 41 publications were included in the systematic review.
Results.
After studying the data from modern literature, some endogenous factors were identified that affect the development of PMDs and MNs of the OM. Some scientists argue that all forms of cancer are the result of a mutation of a normal gene and its transformation into an oncogene, or a chromosomal mutation. Several other researchers have noted the role of hormonal status and metabolic disorders in the development of these diseases. Special attention is given to sex steroid hormones and metabolic abnormalities. According to scientists, there is a positive correlation between exposure to factors such as Candida colonization of the mouth, human papillomavirus infection, and the development of PMDs and MNs of the OM. Many studies have shown a link between vitamin D deficiency and an increased risk of oral cancer. At the same time, elevated levels of copper or decreased levels of zinc, or increased levels of magnesium in biological fluids (blood serum and oral fluid), can increase the risk of PMDs and oral cancer.
Conclusion.
The data presented in the article prove the role of endogenous factors in the development of PMDs and MNs of the OM. At the same time, there is conflicting data on the effect of a particular factor on the human body, which requires further research to obtain reliable results and use them in the prevention of PMDs and MNs of the OM.

Key words:

malignant neoplasms, potentially malignant diseases, oral mucosa, endogenous factors

For Citation

[1]
Mezhevikina G.S., Vagner V.D., Abramova M.Ya., Cherkesova S.I. Endogenous factors contributing to the development of potentially malignant diseases and malignant nodules of the oral mucous membrane (systematic review). Clinical Dentistry (Russia).  2026; 29 (2): 54—59. DOI: 10.37988/1811-153X_2026_2_54

References

  1. Kaprin A.D., Starinsky V.V., Shakhzadova A.O. The state of cancer care in Russia in 2024. − Moscow: P.A. Herzen Moscow Research Institute of Oncology, 2025 — Pp. 4, 27 (In Russian).
  2. Kuleshova S.V., Mukharaeva A.D., Andriutsa O.I., Glybina N.A., Minushkina L.O. Cytological diagnostics of tongue cancer at the outpatient stage. Oncopathology. 2025; 2: 19—22 (In Russian). DOI: 10.17650/2618-7019-2025-8-2-19-22
  3. Dzhuraeva S., Chistenko G., Terekhova T., Ikonnikova A. Oral cancer: risk factors and screening. International reviews: Clinical practice and health. 2020; 2: 7—17 (In Russian). eLIBRARY ID: 44582992
  4. Shumsky A.V. Oncology for dentists. Dentistry for oncologists. Moscow: Vse Pravilno!, 2016. Pp. 5, 27 (In Russain).
  5. Zinovenko O., Luneva L., Bobkova I., Kuratnik E., Sokolova E. Clinical cases of oncological alertness in dental practice. Sovremennaya stomatologiya (Belarus). 2022; 1 (86): 50—54 (In Russian). eLIBRARY ID: 48470677
  6. Syomkin V.A., Rabinovich O.F., Agapitova L.P., Bezrukov A.A., Babichenko I.I. Diagnostic value of optical coherence tomography for oral leukoplakia assessment. Stomatology. 2018; 1: 37—39 (In Russian). DOI: 10.17116/stomat201897137-39
  7. Syomkin V.A., Rabinovich O.F., Babichenko I.I., Bezrukov A.A. Leukoplakia: clinical and pathological diagnosis. Stomatology. 2017; 1: 72—76 (In Russian). DOI: 10.17116/stomat201796172-76
  8. Pecherskaya O.V., Pechersky A.V., Moroz B.T. The role of partial age-related androgen deficiency in the increase of proliferative activity of tissues of the mucous membrane of the mouth. The Dental Institute. 2011; 1 (50): 70—71 (In Russian). eLIBRARY ID: 16553485
  9. Chen X., Cheng Z., Xu J., Wang Q., Zhao Z., Cheng Q., Jiang Q. The dual role of diabetes on oral potentially malignant disorders. Eur J Med Res. 2025; 30 (1): 199. PMID: 40122861
  10. Daye M., Temiz S.A., Isık B. The relationship between lichen planus and metabolic syndrome. J Cosmet Dermatol. 2021; 20 (8): 2635—2639. PMID: 33355985
  11. Aguilar-Martinez E., Morrisroe C., Sharrocks A.D. The ubiquitin ligase UBE3A dampens ERK pathway signalling in HPV E6 transformed HeLa cells. PLoS One. 2015; 10 (3): e0119366. PMID: 25815718
  12. Jing K., Shin S., Jeong S., Kim S., Song K.S., Park J.H., Heo J.Y., Seo K.S., Park S.K., Kweon G.R., Wu T., Park J.I., Lim K. Docosahexaenoic acid induces the degradation of HPV E6/E7 oncoproteins by activating the ubiquitin-proteasome system. Cell Death Dis. 2014; 5 (11): e1524. PMID: 25393480
  13. Shang Q., Peng J., Zhou Y., Chen Q., Xu H. Association of human papillomavirus with oral lichen planus and oral leukoplakia: A meta-analysis. J Evid Based Dent Pract. 2020; 20 (4): 101485. PMID: 33303094
  14. Melo B.A.C., Vilar L.G., Oliveira N.R., Lima P.O., Pinheiro M.B., Domingueti C.P., Pereira M.C. Human papillomavirus infection and oral squamous cell carcinoma — a systematic review. Braz J Otorhinolaryngol. 2021; 87 (3): 346—352. PMID: 33339760
  15. Mikhalev D.E., Baydik O.D., Mukhamedov M.R., Aleksandrov G.O. The role of the human papilloma virus in the development of potentially malignant diseases and squamous cell carcinomas of the oral mucosa. Russian Journal of Dentistry. 2022; 3: 267—276 (In Russian). DOI: 10.17816/1728-2802-2022-26-3-267-276
  16. de la Cour C.D., Sperling C.D., Belmonte F., Syrjänen S., Kjaer S.K. Human papillomavirus prevalence in oral potentially malignant disorders: Systematic review and meta-analysis. Oral Dis. 2021; 27 (3): 431—438. PMID: 32144837
  17. Uehara K., Tanabe Y., Hirota S., Higa S., Toyoda Z., Kurima K., Kina S., Nakasone T., Arasaki A., Kinjo T. Co-expression of low-risk HPV E6/E7 and EBV LMP-1 leads to precancerous lesions by DNA damage. BMC Cancer. 2021; 21 (1): 688. PMID: 34112111
  18. Jiang R., Ekshyyan O., Moore-Medlin T., Rong X., Nathan S., Gu X., Abreo F., Rosenthal E.L., Shi M., Guidry J.T., Scott R.S., Hutt-Fletcher L.M., Nathan C.A. Association between human papilloma virus/Epstein—Barr virus coinfection and oral carcinogenesis. J Oral Pathol Med. 2015; 44 (1): 28—36. PMID: 25040496
  19. Polz-Gruszka D., Morshed K., Stec A., Polz-Dacewicz M. Prevalence of human papillomavirus (HPV) and Epstein—Barr virus (EBV) in oral and oropharyngeal squamous cell carcinoma in south-eastern Poland. Infect Agent Cancer. 2015; 10: 37. PMID: 26462255
  20. Lamont R.J., Fitzsimonds Z.R., Wang H., Gao S. Role of Porphyromonas gingivalis in oral and orodigestive squamous cell carcinoma. Periodontol 2000. 2022; 89 (1): 154—165. PMID: 35244980
  21. Belibasakis G.N., Seneviratne C.J., Jayasinghe R.D., Vo P.T., Bostanci N., Choi Y. Bacteriome and mycobiome dysbiosis in oral mucosal dysplasia and oral cancer. Periodontol 2000. 2024; 96 (1): 95—111. PMID: 38501658
  22. Scully C., el-Kabir M., Samaranayake L.P. Candida and oral candidosis: a review. Crit Rev Oral Biol Med. 1994; 5 (2): 125—57. PMID: 7858080
  23. Alnuaimi A.D., Wiesenfeld D., O›Brien-Simpson N.M., Reynolds E.C., McCullough M.J. Oral Candida colonization in oral cancer patients and its relationship with traditional risk factors of oral cancer: a matched case-control study. Oral Oncol. 2015; 51 (2): 139—45. PMID: 25498921
  24. Roy S.K., Astekar M., Sapra G., Chitlangia R.K., Raj N. Evaluation of candidal species among individuals with oral potentially malignant disorders and oral squamous cell carcinoma. J Oral Maxillofac Pathol. 2019; 23 (2): 302. PMID: 31516244
  25. Deeiam K., Pankam J., Sresumatchai V., Visedketkan P., Jindavech W., Rungraungrayabkul D., Pimolbutr K., Klongnoi B., Khovidhunkit S.P. Presence of Candida and its associated factors in participants attending oral cancer screening in the lower northeastern area of Thailand. BMC Oral Health. 2023; 23 (1): 527. PMID: 37507787
  26. Wang X., Zhang X., Wu S., Zhang W., Yan Z. Is Candida albicans a promoting factor, rather than an inducing factor for oral cancer? —J Oral Microbiol. 2025; 17 (1): 2564694. PMID: 41036106
  27. Brozyna A.A., Hoffman R.M., Slominski A.T. Relevance of vitamin D in melanoma development, progression and therapy. Anticancer Res. 2020; 40 (1): 473—489. PMID: 31892603
  28. Carlberg C., Velleuer E. Vitamin D and the risk for cancer: A molecular analysis. Biochem Pharmacol. 2022; 196: 114735. PMID: 34411566
  29. Khamis A., Salzer L., Schiegnitz E., Stauber R.H., Gül D. The magic triangle in oral potentially malignant disorders: Vitamin D, vitamin D receptor, and malignancy. Int J Mol Sci. 2023; 24 (20): 15058. PMID: 37894739
  30. Koll L., Gül D., Elnouaem M.I., Raslan H., Ramadan O.R., Knauer S.K., Strieth S., Hagemann J., Stauber R.H., Khamis A. Exploiting vitamin D receptor and its ligands to target squamous cell carcinomas of the head and neck. Int J Mol Sci. 2023; 24 (5): 4675. PMID: 36902107
  31. Wu X., Hu W., Lu L., Zhao Y., Zhou Y., Xiao Z., Zhang L., Zhang H., Li X., Li W., Wang S., Cho C.H., Shen J., Li M. Repurposing vitamin D for treatment of human malignancies via targeting tumor microenvironment. Acta Pharm Sin B. 2019; 9 (2): 203—219. PMID: 30972274
  32. Maturana-Ramírez A., Aitken-Saavedra J., Guevara-Benítez A.L., Espinoza-Santander I. Hypovitaminosis D, oral potentially malignant disorders, and oral squamous cell carcinoma: a systematic review. Med Oral Patol Oral Cir Bucal. 2022; 27 (2): e135—e141. PMID: 35218642
  33. Palma V.M., Koerich Laureano N., Frank L.A., Rados P.V., Visioli F. Chemoprevention in oral leukoplakia: challenges and current landscape. Front Oral Health. 2023; 4: 1191347. PMID: 37293562
  34. Gupta J., Aggarwal A. Asadullah, Khan M.H., Agrawal N., Khwaja K.J. Vitamin D in the treatment of oral lichen planus: A pilot clinical study. Journal of Indian Academy of Oral Medicine & Radiology. 2019; 31 (3): 222—227. DOI: 10.4103/jiaomr.jiaomr_97_19
  35. Henn M., Martin-Gorgojo V., Martin-Moreno J.M. Vitamin D in cancer prevention: Gaps in current knowledge and room for hope. Nutrients. 2022; 14 (21): 4512. PMID: 36364774
  36. Bagewadi S.B., Hirpara D.R., Paliwal A., Raiyani B.D., Hafiz A., Vasra H.D., Pampaniya H.M. Estimation of salivary copper, zinc, iron, and copper-to-zinc ratio in oral submucous fibrosis patients: A case-control study. J Contemp Dent Pract. 2022; 23 (3): 303—306. PMID: 35781434
  37. Samadi F.M., Sivakumar N., Sonam M., Sharma P., Suhail S., Ahmad M.K. Quantitative correlation of serum and salivary trace elements in oral squamous cell carcinoma and oral potentially malignant disorders: An institution-based biochemical analysis. J Oral Maxillofac Pathol. 2024; 28 (3): 434—442. PMID: 39670132
  38. Li Y., Liang J., Chen Y., Wang Y. The mechanism of copper homeostasis and its role in disease. iLABMED. 2023; 2: 109—120. DOI: 10.1002/ila2.22
  39. Shetty S.R., Babu S., Kumari S., Shetty P., Hegde S., Karikal A. Status of trace elements in saliva of oral precancer and oral cancer patients. J Cancer Res Ther. 2015; 11 (1): 146—9. PMID: 25879353
  40. Ayinampudi B.K., Narsimhan M. Salivary copper and zinc levels in oral pre-malignant and malignant lesions. J Oral Maxillofac Pathol. 2012; 16 (2): 178—82. PMID: 22923887
  41. Aziz N.Z., Arathi K., Prasad B.G., Desai D., Shetty S.J., Shahid M. Evaluation of magnesium levels in blood and saliva of oral squamous cell carcinoma and potentially malignant disorders by xylidyl blue method. J Oral Maxillofac Pathol. 2018; 22 (1): 147. PMID: 29731579

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Received

March 10, 2026

Accepted

May 18, 2026

Published on

July 4, 2026