Moscow, Moscow, Russian Federation
Moscow, Moscow, Russian Federation
from 01.01.2013 until now
Moscow, Moscow, Russian Federation
Moscow, Moscow, Russian Federation
Moscow, Moscow, Russian Federation
Moscow, Moscow, Russian Federation
from 01.01.2018 until now
Moscow, Moscow, Russian Federation
UDK 616.31 Стоматология. Заболевания ротовой полости и зубов
GRNTI 76.29 Клиническая медицина
Data from domestic and foreign literature indicate a close pathogenetic relationship between the expression of cancer markers p16 and p53, tumor suppressor proteins, and the invasion of human papillomavirus (HPV) in patients with precancerous lesions of the oral mucosa. Thus, it seems advisable to evaluate the frequency of detection of the expression of cancer markers p16 and p53 by immunohistochemical examination in patients with HPV-positive and HPV-negative dysplastic lesions of the oral mucosa. The aim is to increase the effectiveness of the diagnosis of lesions of the oral mucosa associated with epithelial dysplasia. Materials and methods. The study involved 50 patients with established diagnoses of leukoplakia and lichen planus with signs of epithelial dysplasia. After surgery, all patients underwent an immunohistochemical study of the expression of proteins p16 and p53 and a PCR study for papillomavirus. The ratio of the frequency of detection of cancer marker expression in subgroups depending on the HPV status was evaluated. Results. There were no statistically significant differences in the frequency of detection of p53 (p = 0.161) and p16 (p = 0.21) cancer marker expressions depending on the HPV status of patients. There were also statistically insignificant differences in the frequency of detection of the expression of cancer markers p16 (p = 0.333) and p53 (p = 0.178) depending on gender. The HPV-positive status of patients with epithelial dysplasia of the oral mucosa was statistically significantly more often associated with the female sex (p = 0.008). Conclusion. The assessment of the expression of proteins p16 and p53 is not a reliable method for diagnosing oral epithelial dysplasia and associated papillomavirus infection. There is a need to search for alternative and more accurate molecular markers of the disease, as well as a greater number of observations.
epithelial dysplasia, tumor suppressor protein, human papillomavirus, diagnosis of potentially malignant diseases, oral mucosa, p16, p53
1. Abdulmajeed A.A., Farah C.S. Can immunohistochemistry serve as an alternative to subjective histopathological diagnosis of oral epithelial dysplasia? // Biomark Cancer. – 2013;5:49-60. doi:https://doi.org/10.4137/BIC.S12951.
2. Anaya-Saavedra G., Vázquez-Garduño M. Oral HPV-associated dysplasia: is koilocytic dysplasia a separate entity? // Front Oral Health. – 2024;5:1363556. doi:https://doi.org/10.3389/froh.2024.1363556.
3. Bertoli H.K., Rasmussen C.L., Sand F.L., Albieri V., Norrild B., Verdoodt F., Kjaer S.K. Human papillomavirus and p16 in squamous cell carcinoma and intraepithelial neoplasia of the vagina // Int J Cancer. – 2019;145(1):78-86. doi:https://doi.org/10.1002/ijc.32078.
4. Pandya J.A., Boaz K., Natarajan S., Manaktala N., Nandita K.P., Lewis A.J. A correlation of immunohistochemical expression of TP53 and CDKN1A in oral epithelial dysplasia and oral squamous cell carcinoma // J Cancer Res Ther. – 2018;14(3):666-670. doi:https://doi.org/10.4103/0973-1482.180683.
5. de la Cour C.D., Sperling C.D., Belmonte F., Syrjänen S., Verdoodt F., Kjaer S.K. Prevalence of human papillomavirus in oral epithelial dysplasia: Systematic review and meta-analysis // Head Neck. – 2020;42(10):2975-2984. doi:https://doi.org/10.1002/hed.26330.
6. Gupta S., Jawanda M.K., Madhushankari G.S. Current challenges and the diagnostic pitfalls in the grading of epithelial dysplasia in oral potentially malignant disorders: A review // J Oral Biol Craniofac Res. – 2020;10(4):788-799. doi:https://doi.org/10.1016/j.jobcr.2020.09.005.
7. Gurín D., Slávik M., Shatokhina T., Kazda T., Šána J., Slabý O., Hermanová M. Current Perspective on HPV-Associated Oropharyngeal Carcinomas and the Role of p16 as a Surrogate Marker of High-Risk HPV // Klin Onkol. – 2019;32(4):252-260. English. doi:https://doi.org/10.14735/amko2019252.
8. Iocca O., Sollecito T.P., Alawi F., Weinstein G.S., Newman J.G., De Virgilio A., Di Maio P., Spriano G., Pardiñas López S., Shanti R.M. Potentially malignant disorders of the oral cavity and oral dysplasia: A systematic review and meta-analysis of malignant transformation rate by subtype // Head Neck. – 2020;42(3):539-555. doi:https://doi.org/10.1002/hed.26006.
9. Kuo K.T., Hsiao C.H., Lin C.H., Kuo L.T., Huang S.H., Lin M.C. The biomarkers of human papillomavirus infection in tonsillar squamous cell carcinoma-molecular basis and predicting favorable outcome // Mod Pathol. – 2008;21(4):376-386. doi:https://doi.org/10.1038/modpathol.3800979.
10. Lerman M.A., Almazrooa S., Lindeman N., Hall D., Villa A., Woo S.B. HPV-16 in a distinct subset of oral epithelial dysplasia // Mod Pathol. – 2017;30(12):1646-1654. doi:https://doi.org/10.1038/modpathol.2017.71.
11. Lorini L., Bescós Atín C., Thavaraj S., Müller-Richter U., Alberola Ferranti M., Pamias Romero J., Sáez Barba M., de Pablo García-Cuenca A., Braña García I., Bossi P., Nuciforo P., Simonetti S. Overview of Oral Potentially Malignant Disorders: From Risk Factors to Specific Therapies // Cancers (Basel). – 2021;13(15):3696. doi:https://doi.org/10.3390/cancers13153696.
12. More P., Kheur S., Patekar D., Kheur M., Gupta A.A., Raj A.T., Patil S. Assessing the nature of the association of human papillomavirus in oral cancer with and without known risk factors // Transl Cancer Res. – 2020;9(4):3119-3125. doi:https://doi.org/10.21037/tcr.2020.03.81.
13. Nauta I.H., Rietbergen M.M., van Bokhoven A.A.J.D., Bloemena E., Lissenberg-Witte B.I., Heideman D.A.M., Baatenburg de Jong R.J., Brakenhoff R.H., Leemans C.R. Evaluation of the eighth TNM classification on p16-positive oropharyngeal squamous cell carcinomas in the Netherlands and the importance of additional HPV DNA testing // Ann Oncol. – 2018;29(5):1273-1279. doi:https://doi.org/10.1093/annonc/mdy060. PMID: 29438466.
14. Normando A.G.C., dos Santos E.S., Sá Jamile de Oliveira, Busso-Lopes A.F., De Rossi T., Patroni Fábio Malta de Sá, Granato D.C., Guerra E.N.S., Santos-Silva A.R., Lopes M.A., Paes Leme A.F. A meta-analysis reveals the protein profile associated with malignant transformation of oral leukoplakia // Front. Oral. Health. – 2023;4:1088022. doi:https://doi.org/10.3389/froh.2023.1088022
15. Radzki D., Kusiak A., Ordyniec-Kwaśnica I., Bondarczuk A. Human papillomavirus and leukoplakia of the oral cavity: a systematic review // Postepy Dermatol Alergol. – 2022;39(3):594-600. doi:https://doi.org/10.5114/ada.2021.107269.
16. Ranganath K., Feng A.L., Franco R.A., Varvares M.A., Faquin W.C., Naunheim M.R., Saladi S.V. Molecular Biomarkers of Malignant Transformation in Head and Neck Dysplasia // Cancers (Basel). – 2022;14(22):5581. doi:https://doi.org/10.3390/cancers14225581.
17. Sabu A., Mouli N.V.R., Tejaswini N., Rohit V., Nishitha G., Uppala D. Human Papillomavirus Detection in Oropharyngeal Squamous Cell Carcinoma Using p16 Immunohistochemistry // Int J Appl Basic Med Res. – 2019;9(4):212-216. doi:https://doi.org/10.4103/ijabmr.IJABMR_221_18.
18. 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(3):209-249. doi:https://doi.org/10.3322/caac.21660.
19. Thankappan P., Ramadoss M.N., Joseph T.I., Augustine P.I., Shaga I.B., Thilak J. Human Papilloma Virus and Cancer Stem Cell markers in Oral Epithelial Dysplasia-An Immunohistochemical Study // Rambam Maimonides Med J. – 2021;12(4):e0028. doi:https://doi.org/10.5041/RMMJ.10451.
20. Wang H., Sun R., Lin H., Hu W.H. P16INK4A as a surrogate biomarker for human papillomavirus-associated oropharyngeal carcinoma: consideration of some aspects // Cancer Sci. – 2013;104(12):1553-1559. doi:https://doi.org/10.1111/cas.12287.
21. Yadav P., Malik R., Balani S., Nigam R.K., Jain P., Tandon P. Expression of p-16, Ki-67 and p-53 markers in dysplastic and malignant lesions of the oral cavity and oropharynx // J Oral Maxillofac Pathol. – 2019;23(2):224-230. doi:https://doi.org/10.4103/jomfp.JOMFP_299_18.
22. Adil'baev G.B., Shipilova V.V., Kydyrbaeva G.Zh., Sadyk Zh.T., Adil'bay D.G., Sokolenko E.G., Medetbekova E.P. Rezul'taty issledovaniya markerov proliferacii Ki 67 i r16 u VPCh associirovannyh i VPCh negativnyh pacientov rakom polosti rta i rotoglotki v Kazahstane. Onkologiya i radiologiya Kazahstana. 2016;3:172-175. [G.B. Adilbaev, V.V. Shipilova, G.J. Kydyrbayeva, J.T. Sadyk, D.G. Adilbai, E.G. Sokolenko, E.P. Medetbekova. The results of the study of markers of proliferation of Ki 67 and p 16u HPV associated and HPV negative patients with oral and oropharyngeal cancer in Kazakhstan. Oncology and Radiology of Kazakhstan. 2016;3:172-175. (In Russ.)]. https://oncojournal.kz/wp-content/uploads/2016/2016.3.41_14.pdf
23. Ivina A.A. Sovremennye predstavleniya o ploskokletochnom rake slizistoy obolochki rta. Arhiv patologii. 2020;82(3):55-60. [A/A. Ivina. Modern perspectives of oral squamous cell carcinoma. Russian Journal of Archive of Pathology. 2020;82(3):55-60. (In Russ.)]. https://doi.org/10.17116/patol20208203155
24. Stukan' A.I., Chuhray O.Yu., Porhanov V.A., Bodnya V.N. Vzaimosvyaz' ekspressii p53 i p16INK4A s kliniko-morfologicheskimi harakteristikami bol'nyh ploskokletochnym rakom golovy i shei. Arhiv patologii. 2019;81(3):12-18. [A.I. Stukan, O.Yu. Chukhray, V.A. Porkhanov, V.N. Bodnya. Association of the expression of p53 and p16INK4A with the clinical and morphological characteristicsof patients with head and neck squamous cell cancer (in Russian only). Russian Journal of Archive of Pathology. 2019;81(3):12-18. (In Russ.)]. doi:https://doi.org/10.17116/patol20198103112