Tula, Tula, Russian Federation
Sankt-Peterburg, St. Petersburg, Russian Federation
Russian Federation
Russian Federation
UDK 61 Медицина. Охрана здоровья
For a more accurate prediction of tumor behavior and individualization of treatment approach, it is necessary to improve new methods of early diagnosis of precancerous conditions. The article provides an overview of the modern understanding of the mechanisms of gene p16 expression as a factor in tumor growth. Data on the relevance of studying the pathogenesis of tumor blast transformation in invasive breast cancer are presented. These tumors require the combined interdisciplinary work of highly qualified specialists and ultra-modern technologies to achieve a positive result. The link between the formation of malignant breast tumors and human papillomavirus is described. The purpose of this study was to review the futuristically significant immunohistochemical analysis of p16 in patients of different age groups with common cervical cancer and breast cancer. The possibility of using the determination of p16 expression as a prognostic marker for breast cancer is shown, as well as the results of studying the expression of p16 and p53 in triple-negative breast cancer. The data reflecting the dependence of the suppressor function efficiency on the localization of p16 expression in squamous cell carcinoma of the cervix are analyzed. The dependence of p16INK4a expression on the severity of malignant cervical lesions is indicated, and the effect of chemotherapy on p16 expression is considered. By studying and applying information on the ontogenetic variability of the p16 gene, it is possible to significantly increase the accuracy of predicting the clinical and pathomorphological course of cancer of any nature of occurrence and to select adequate therapy: gene, chemotherapy, radiation therapy.
p16 gene, tumor blast transformation, breast carcinoma, human papillomavirus, cervical cancer
1. Aleksandrova A.K., Smol'yannikova V.A. Sovremennye predstavleniya o roli v kletochnom cikle belkov-ingibitorov ciklin-zavisimyh kinaz r16 i r27 // Kubanskiy nauchnyy medicinskiy vestnik. 2016. №1. URL: https://cyberleninka. ru/article/n /sovremennye-predstavleniya-o-roli-v-kletochnom-tsikle-belkov-ingibitorov-tsiklin-zavisimyh-kinaz-r16-i-r-27
2. Alyautdina O.S., Sinicyna O.V. Znachenie testa na onkobelok r16ink4a v algoritme diagnostiki raka sheyki matki // Mezhdunarodnyy zhurnal prikladnyh i fundamental'nyh issledovaniy. 2016. № 11-1. S. 58-60;
3. Associaciya onkologov Rossii. Klinicheskie rekomendacii «Rak sheyki matki», 2020 g.
4. Bebneva T.N. Ocenka ekspressii proteinov p16 i Ki-67 kak markerov cervikal'noy intraepitelial'noy neoplazii pri beremennosti // Akusherstvo i ginekologiya: Novosti. Mneniya. Obucheniya. 2018. №3 (21). URL: https://cyberleninka. ru/article/n/otsenka-ekspressii-proteinov-p16-i-ki-67-kak-markerov-tservikalnoy-intraepitelialnoy-neoplazii-pri-beremennosti.
5. Vaneeva, E.V., Turubanova A.N., Sarpova M.V. i dr. Prognosticheskoe znachenie sochetannoy ekspressii r53 i r16 pri diffuznoy V-krupnokletochnoy limfome // Vestnik gematologii. 2022. T.18,№2. S.43-44.
6. Dimitriadi T.A., Burcev D.V., Dzhenkova E.A. i dr. Prognosticheskoe znachenie markerov Ki-67 i p16ink4a v gistologicheskoy diagnostike stepeni displazii sheyki matki // Research'n Practical Medicine Journal. 2020. №1. URL: https://cyberleninka. ru/article/n/prognosticheskoe-znachenie-markerov-ki-67-i-p16-ink4a-v-gistologicheskoy-diagnostike-stepeni-displazii-sheyki-matki
7. Kazachkova E.A., Goshgarly A.V., Voropaeva E.E. Ekspressiya belka r16ink4a pri giperplazii endometriya, associirovannoy s hronicheskim endometritom - Tekst: elektronnyy // Ural'skiy medicinskiy zhurnal. 2018. T. 157, № 2. S. 97-100.
8. Kaprin A.D., Starinskiy V.V., Petrova G.V. Sostoyanie onkologicheskoy pomoschi v Rosii v 2018 godu. M., 2019. 250 s.
9. Kit O.I., Kovalenko, N.V. Maksimov A.Yu. i dr. Bioinformacionnye i klinicheskie aspekty identifikacii differencial'no ekspressiruemyh genov opuholevymi kletkami pri endometrial'noy karcinome i redkih formah raka tela matki // Medicinskiy vestnik Severnogo Kavkaza. 2023. T.18, №1. S. 37-41.
10. Kishore V., Patil A.G. Ekspressiya belka p16ink4a pri cervikal'noy intraepitelial'noy neoplazii i invazivnoy karcinome sheyki matki. J Clin Diagn Res. 2017 Sep;11(9): EC17-EC20. doi:https://doi.org/10.7860/JCDR/2017/29394.10644. Epub 2017 Sep 1. PMID: 29207716; PMCID: PMC5713738.
11. Popov S.V., Guseynov R.G., Skryabin O.N. i dr. Molekulyarno-geneticheskie i citogeneticheskie harakteristiki sporadicheskogo raka pochki: obzor literatury // Onkourologiya. 2022. №3. S.107-115.
12. Klinyshkova T.V., Mironova O.N. Vliyanie inozin pranobeksa na ekspressiyu r16, Ki-67 u bol'nyh s VPCh-associirovannymi cervikal'nymi intraepitelial'nymi neoplaziyami // Ginekologiya. 2018. №4. URL: https://cyberleninka.ru/article/n/vliyanie-inozin-pranobeksa-na-ekspressiyu-r16-ki-67-u-bolnyh-s-vpch-assotsiirovannymi-tservikalnymi-intraepitelialnymi-neoplaziyami
13. Shiman O.V., Aleksinskiy V.S. Osobennosti lokal'nogo immunnogo otveta i immunogistohimicheskie markery prognoza pri rake sheyki matki // Zhurnal GrGMU. 2022. №6. URL:https://cyberleninka.ru/article/n/osobennosti-lokalnogo-immunnogo-otveta-i-immunogistohimicheskie-arkery-prognoza-pri-rake-sheyki-matki.
14. Cavalcante Junior, Pinheiro L.C.P., Almeida C.U.R. et al. Association of breast cancer with infection caused by human papillomavirus (HPV), on Northeast Brazil: molecular evidence. Clinics (Sao Paulo). October 18, 2018; 73: e465. doi:https://doi.org/10.6061/blades/2018 /e465. PMID: 30365827; PMCID: PMC6172977.
15. Ferris R.L., Flamand Y., Weinstein G.S. et al. Phase II randomized trial of transoral surgery and low-dose intensity modulated radiation therapy in resectable p16+ locally advanced oropharynx cancer: an ECOG-ACRIN cancer research group trial (E3311). J. Clin. Oncol. Off J. Am. Soc. Clin. Oncol. [Published on-line October 26]. 2021:JCO2101752. Doi:https://doi.org/10.1200/JCO.21.01752.
16. Fu H.C., Chuang I.C., Yang Y.C. et al. Low r16ink4A expression associated with high expression of cancer stem cell markers predicts poor prognosis in cervical cancer after radiotherapy. Int J Mol Sci. 2018 Aug 27;19(9):2541. doi:https://doi.org/10.3390/ijms19092541. PMID: 30150594; PMCID: PMC6164400.
17. Hajjar S.S., Dil A.M., Reder-Hey K.E. et al. The effect of adjuvant chemotherapy regimens for breast cancer on the expression of the biomarker strategy, p16ink4a. Cancer Review NCI. 2020, December 18; 4 (6): pkaa082. doi:https://doi.org/10.1093/jncics/pkaa082. PMID: 33409457; PMCID: PMC7771421.
18. Hashmi A.A., Naz S., Hashmi K.K. et al. Prognostic value of immunohistochemical expression of p16 and p53 in triple negative breast cancer. BMC Clin Pathol. October 3, 2018;18:9. doi:https://doi.org/10.1186/s12907-018-0077-0 . PMID: 30305801; PMCID: PMC6171321.
19. Human papillomavirus and p16 protein expression as prognostic biomarkers in mobile tongue cancer // Acta Otolaryngol. 2017 Oct;137(10):1121-1126. doi:https://doi.org/10.1080/00016489.2017.1339327. Epub 2017 Jul 2.
20. Inoue K., Fry E.A. Aberrant expression of p16ink4a in human cancer - a new biomarker? Cancer Res Rev. 2018 Mar; 2 (2): 10.15761 / CR.1000145. doi: 10.15761 /CR.1000145. Epub 2018, January 15. PMID: 29951643; PMCID: PMC6018005.
21. Johnson M.E., Cantalupo P.G., Pipas J.M. Identification of head and neck cancer subtypes based on human papillomavirus presence and E2F-regulated gene expression. mSphere. 2018 Jan 10; 3(1). pii: e00580-17. https://doi.org/10.1128/mSphere.00580-17.
22. Kozhitsky S., Grzhegzholka D.J., Glatel-Palchinskaya N. et al. Expression of p16 and SATB1 in invasive breast cancer treatment is a preliminary study. In Vivo. July-August 2018; 32 (4): 731-736. doi:https://doi.org/10.21873/invivo.11301. PMID: 29936452; PMCID: PMC6117790.
23. Lewis J.S.Jr., Beadle B., Bishop J.A. et al. Human papillomavirus testing in head and neck carcinomas: guideline from the Sollege of American pathologists. Arch Pathol Lab Med. 2018 May; 142(5): 559-97. https://doi.org/10.5858/arpa.2017-0286-CP.
24. Ma D.J., Price K., Eric M.J. et al. Long-term results for MC1273, a phase II evaluation of de-escalated adjuvant radiation therapy for human papillomavirus associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC). Int. J. Radiat. Oncol. 2021;111(Suppl. 3):S61. Doi:https://doi.org/10.1016/j. ijrobp.2021.07.155.
25. Mendasa S., Fernandez-Yrigoyen J., Santamaria E. et al. The absence of nuclear p16 is a diagnostic and independent prognostic biomarker in squamous cell carcinoma of the cervix. Cervical carcinoma. March 19, 2020, 21 (6):2125. doi:https://doi.org/10.3390/ijms21062125. PMID: 32204550; PMCID: PMC7139571.
26. Mohammadizade F., Nasri F. Expression of p16 in human breast cancer and its relation to clinical and pathological parameters. Adv Biomed dated June 28, 2023;12:154. doi:https://doi.org/10.4103/abr.abr_180_22. PMID: 37564443; PMCID: PMC10410420.
27. Ottria L., Candotto V., Cura F., et al. HPV acting on E-cadherin, p53 and p16 literature review. J. Biol. Regul. Homeost. Agents. 2018;32(2 Suppl. 1):73-9.
28. Pandey A., Chandra S., Nautiyal R. et al. Expression of p16ink4a and human papillomavirus 16 with associated risk factors in precancerous and malignant lesions of the cervix. Cancer of Western Asia. October-December 2018; 7(4):236-239. doi:https://doi.org/10.4103/sajt.sajt_118_17. PMID: 30430091; PMCID: PMC6190388.
29. Prigge E.S., Arbyn M., Doeberitz M. von K., Reuschenbach M. Diagnostic accuracy of p16ink4a immunohistochemistry in oropharyngeal squamous cell carcinomas: A systematic review and meta-analysis. Int. J. Cancer. 2017;140(5):1186-98. Doi: https://doi.org/https://doi.org/10.1002/ijc.30516.
30. Qi D., Li J., Jiang M. et al. The relationship between promoter methylation of p16 gene and bladder cancer risk: a meta-analysis // Int. J. Clin. Exp. Med. 2015. Vol. 8, N 11. P. 20701-20711.
31. Rana M.K., Rana A.P.S., Khera U. Expression of p53 and p16 in the tissue for many glands in the rocket: indicates a prognostic value or recognition. Cureus 2021 November 9; 13 (11): e19395. doi:https://doi.org/10.7759/cureus.19395. PMID: 34925997; PMCID: PMC8654126.
32. Salih M.M., Nigo A.A., Eed E.M. Comparative significance of p16 protein expression for breast cancer. In Vivo. January-February 2022; 36(1):336-340. doi:https://doi.org/10.21873/in vivo.12707. PMID: 34972731; PMCID: PMC8765164.
33. Safvan-Zaiter H., Wagner N., Wagner K.D. P16ink4a is something more than a marker of aging. Life (Basel). 2022 August 28;12 (9):1332. doi:https://doi.org/10.3390/life12091332. PMID: 36143369; PMCID: PMC9501954.
34. Sean J., Song R., Fuemmeler B.F. et al. The biological marker of aging p16ink4a in T cells and the risk of breast cancer. Cancer diseases (Basel). October 26, 2020; 12 (11):3122. doi: 10.3390/ cancers12113122. Error B: Cancers (Basel). January 17, 2021; 13 (2): PMID: 33114473; PMCID: PMC7692397.
35. Sedghizadeh P.P., Billington W.D., Paxton D., et al. Is p16-positive oropharyngeal squamous cell carcinoma associated with favorable prognosis? A systematic review and meta-analysis. Oral Oncol. 2016;54:15-27. Doi:https://doi.org/10.1016/j.oraloncology.2016.01.002.
36. Stukan A.I., Porkhanov V.A., Bodnya V.N. Clinical significance of r16-positive status and high index of proliferative activity in patients with oropharyngeal squamous cell carcinoma. Siberian journal of oncology. 2020;19(2):41-48. https://doi.org/10.21294/1814-4861-2020-19-2-41-48
37. Sung H., Ferley J., Siegel R.L. et al. Global Cancer Statistics 2020: GLOBOCAN estimates of morbidity and mortality worldwide for 36 types of cancer in 185 countries. CA Cancer J Clin. 2021 May; 71(3):209-249. doi:https://doi.org/10.3322/caac.21660. Epub 2021 February 4. PMID: 33538338.
38. Wang H., Zhang Y., Bai W. et al. Feasibility of immunohistochemical p16 staining in the diagnosis of human papillomavirus infection in patients with squamous cell carcinoma of the head and neck: A Systematic Review and Meta-Analysis. Front. Oncol. 2020;10. Doi:https://doi.org/10.3389/fonc.2020.524928.
39. Yap M.L., Allo G., Cuartero J. et al. Prognostic significance of human papilloma virus and p16 expression in patients with vulvar squamous cell carcinoma who received radiotherapy. Clin Oncol (R Coll Radiol). 2018 Apr;30(4):254-261. doi:https://doi.org/10.1016/j.clon.2018.01.011. Epub 2018 Feb 12. PMID: 29449057.
40. Yovanovich D.V., Mitrovich S.L., Milosavlevich M.Z. et al. Breast cancer and p16: role in proliferation, malignant transformation and progression. Healthcare (Basel). September 21, 2021;9 (9):1240. doi:https://doi.org/10.3390/healthcare9091240. PMID: 34575014; PMCID: PMC8468846.
41. Alexandrova A.K., Smolyannikova V.A. Modern ideas about the role of cyclin-dependent kinase inhibitor proteins p16 and p27 in the cell cycle // Kuban Scientific Medical Bulletin. 2016. №1. URL: https://cyberleninka.ru/article/n/sovremennye-predstavleniya-o-roli-v-kletochnom-tsikle-belkov-ingibitorov-tsiklin-zavisimyh-kinaz-r16-i-r-27.
42. Alyautdina O.S., Sinitsyna O.V. The significance of the test for cancer protein p16ink4a in the algorithm for diagnosing cervical cancer // International Journal of Applied and Fundamental Research. - 2016. - No. 11-1. - pp. 58-60.
43. Association of Oncologists of Russia. Clinical recommendations "Cervical cancer", 2020.
44. Bebneva T.N. Evaluation of the expression of proteins p16 and Ki-67 as markers of cervical intraepithelial neoplasia during pregnancy // Obstetrics and gynecology: News. Opinions. Training. 2018. №3 (21). URL: https://cyberleninka.ru/article/n/otsenka-ekspressii-proteinov-p16-i-ki-67-kak-markerov-tservikalnoy-intraepitelialnoy-neoplazii-pri-beremennosti.
45. Vaneeva, E.V., Turubanova A.N., Sarpova M.V. and others. The prognostic value of the combined expression of p53 and p16 in diffuse B-large cell lymphoma // Bulletin of Hematology. 2022. Vol.18, No.2. pp.43-44.
46. Dimitriadi T.A., Burtsev D.V., Jenkova E.A. et al. Prognostic value of markers Ki-67 and p16ink4a in histological diagnosis of cervical dysplasia degree // Research'n Practical Medicine Journal. 2020. No.1. URL: https://cyberleninka.ru/article/n/prognosticheskoe-znachenie-markerov-ki-67-i-p16-ink4a-v-gistologicheskoy-diagnostike-stepeni-displazii-sheyki-matki.
47. Kazachkova E.A., Goshgarly A.V., Voropaeva E.E. Expression of r16ink4a protein in endometrial hyperplasia associated with chronic endometritis / - Text: electronic // Ural Medical Journal. 2018. Vol. 157, No. 2. pp. 97-100.
48. Kaprin A.D., StarinskiiV.V., PetrovaG.V. Sostoyanie onkologicheskoi pomoshchi v Rossii v 2018 godu. M., 2019. 250 s.
49. Kit O.I., Kovalenko, N.V. Maksimov A.Yu. et al. Bioinformatic and clinical aspects of the identification of differentially expressed genes by tumor cells in endometrial carcinoma and rare forms of uterine body cancer // Medical Bulletin of the North Caucasus. 2023. Vol.18, No. 1. pp. 37-41.
50. Kishore V., Patil A.G. Expression of p16ink4a protein in cervical intraepithelial neoplasia and invasive cervical carcinoma. J Clin Diagn Res. 2017 Sep;11(9): EC17-EC20. doi:https://doi.org/10.7860/JCDR/2017/29394.10644. Epub 2017 Sep 1. PMID: 29207716; PMCID: PMC5713738.
51. Popov S.V., Huseynov R.G., Scriabin O.N. and others. Molecular genetic and cytogenetic characteristics of sporadic kidney cancer: a literature review // Oncourology. 2022. No.3. pp.107-115.
52. Klinyshkova T.V., Mironova O. N. The effect of inosine pranobex on the expression of p16, Ki-67 in patients with HPV-associated cervical intraepithelial neoplasia // Gynecology. 2018. №4. URL: https://cyberleninka.ru/article/n/vliyanie-inozin-pranobeksa-na-ekspressiyu-r16-ki-67-u-bolnyh-s-vpch-assotsiirovannymi-tservikalnymi-intraepitelialnymi-neoplaziyami.
53. Shiman O.V., Aleksinsky V.S. Features of the local immune response and immunohistochemical markers of prognosis in cervical cancer // Journal of GrSMU. 2022. No.6. URL:https://cyberleninka.ru/article/n/osobennosti-lokalnogo-immunnogo-otveta-i-immunogistohimicheskie-arkery-prognoza-pri-rake-sheyki-matki.
54. Cavalcante Junior, Pinheiro L.C.P., Almeida C.U.R. et al. Association of breast cancer with infection caused by human papillomavirus (HPV), on Northeast Brazil: molecular evidence. Clinics (Sao Paulo). October 18, 2018; 73: e465. doi:https://doi.org/10.6061/blades/2018 /e465. PMID: 30365827; PMCID: PMC6172977
55. Ferris R.L., Flamand Y., Weinstein G.S., et al. Phase II randomized trial of transoral surgery and low-dose intensity modulated radiation therapy in resectable p16+ locally advanced oropharynx cancer: An ECOG-ACRIN Cancer Research Group Trial (E3311). J. Clin. Oncol. Off J. Am. Soc. Clin. Oncol. [Published on-line October 26]. 2021:JCO2101752. Doi:https://doi.org/10.1200/JCO.21.01752.
56. Fu H.C., Chuang I.C., Yang Y.C. et al. Low r16ink4A expression associated with high expression of cancer stem cell markers predicts poor prognosis in cervical cancer after radiotherapy. Int J Mol Sci. 2018 Aug 27;19(9):2541. doi: 0.3390/ijms19092541. PMID: 30150594; PMCID: PMC6164400.
57. Hajjar S.S., Dil A.M., Reder-Hey K.E. et al. The effect of adjuvant chemotherapy regimens for breast cancer on the expression of the biomarker strategy, p16ink4a. Cancer Review NCI. 2020, December 18; 4 (6): pkaa082. doi:https://doi.org/10.1093/jncics/pkaa082. PMID: 33409457; PMCID: PMC7771421.
58. Hashmi A.A., Naz S., Hashmi K.K. et al. Prognostic value of immunohistochemical expression of p16 and p53 in triple negative breast cancer. BMC Clin Pathol. October 3, 2018;18:9. doi:https://doi.org/10.1186/s12907-018-0077-0 . PMID: 30305801; PMCID: PMC6171321.
59. Human papillomavirus and p16 protein expression as prognostic biomarkers in mobile tongue cancer. // Acta Otolaryngol. 2017 Oct;137(10):1121-1126. doi:https://doi.org/10.1080/00016489.2017.1339327. Epub 2017 Jul 2.
60. Inoue K., Fry E.A. Aberrant expression of p16ink4a in human cancer - a new biomarker? Cancer Res Rev. 2018 Mar; 2 (2): 10.15761 / CR.1000145. doi: 10.15761 /CR.1000145. Epub 2018, January 15. PMID: 29951643; PMCID: PMC6018005.
61. Johnson M.E., Cantalupo P.G., Pipas J.M. Identification of head and neck cancer subtypes based on human papillomavirus presence and E2F-regulated gene expression. mSphere. 2018 Jan 10; 3(1). pii: e00580-17. https://doi.org/10.1128/mSphere.00580-17.
62. Kozhitsky S., Grzhegzholka D.J., Glatel-Palchinskaya N. et al. Expression of r16 and SATB1 in invasive breast cancer treatment is a preliminary study. In Vivo. July-August 2018; 32 (4): 731-736. doi:https://doi.org/10.21873/invivo.11301. PMID: 29936452; PMCID: PMC6117790.
63. Lewis J.S.Jr., Beadle B., Bishop J.A. et al. Human papillomavirus testing in head and neck carcinomas: guideline from the College of American pathologists. Arch Pathol Lab Med. 2018 May; 142(5): 559-97. https://doi.org/10.5858/arpa.2017-0286-CP
64. Ma D.J., Price K., Eric M.J., et al. Long-Term Results for MC1273, a phase II evaluation of de-escalated adjuvant radiation therapy for human papillomavirus associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC). Int. J. Radiat. Oncol. 2021;111(Suppl. 3):S61. Doi:https://doi.org/10.1016/j. ijrobp.2021.07.155.
65. Mendasa S., Fernandez-Yrigoyen J., Santamaria E. et al. The absence of nuclear p16 is a diagnostic and independent prognostic biomarker in squamous cell carcinoma of the cervix. Cervical carcinoma. March 19, 2020, 21 (6):2125. doi:https://doi.org/10.3390/ijms21062125. PMID: 32204550; PMCID: PMC7139571.
66. Mohammadizade F., Nasri F. Expression of r16 in human breast cancer and its relation to clinical and pathological parameters. Adv Biomed dated June 28, 2023;12:154. doi:https://doi.org/10.4103/abr.abr_180_22. PMID: 37564443; PMCID: PMC10410420.
67. Ottria L., Candotto V., Cura F., et al. HPV acting on E-cadherin, p53 and p16 literature review. J. Biol. Regul. Homeost. Agents. 2018;32(2 Suppl. 1):73-9.
68. Pandey A., Chandra S., Nautiyal R. et al. Expression of p16ink4a and human papillomavirus 16 with associated risk factors in precancerous and malignant lesions of the cervix. Cancer of Western Asia. October-December 2018; 7(4):236-239. doi:https://doi.org/10.4103/sajt.sajt_118_17. PMID: 30430091; PMCID: PMC6190388.
69. Prigge E.S., Arbyn M., Doeberitz M. von K., Reuschenbach M. Diagnostic accuracy of p16ink4a immunohistochemistry in oropharyngeal squamous cell carcinomas: A systematic review and meta-analysis. Int. J. Cancer. 2017;140(5):1186-98. Doi: https:// doi.org/10.1002/ijc.30516
70. Qi D., Li J., Jiang M. et al. The relationship between promoter methylation of p16 gene and bladder cancer risk: a meta-analysis // Int. J. Clin. Exp. Med. 2015. Vol. 8, N 11. P. 20701-20711.
71. Rana M.K., Rana A.P.S., Khera U. Expression of p53 and p16 in the tissue for many glands in the rocket: indicates a prognostic value or recognition. Cureus 2021 November 9; 13 (11): e19395. doi:https://doi.org/10.7759/cureus.19395. PMID: 34925997; PMCID: PMC8654126.
72. Salih M.M., Nigo A.A., Eed E.M. Comparative significance of p16 protein expression for breast cancer. In Vivo. January-February 2022; 36(1):336-340. doi:https://doi.org/10.21873/in vivo.12707. PMID: 34972731; PMCID: PMC8765164.
73. Safvan-Zaiter H., Wagner N., Wagner K.D. P16ink4A is something more than a marker of aging. Life (Basel). 2022 August 28;12 (9):1332. doi:https://doi.org/10.3390/life12091332. PMID: 36143369; PMCID: PMC9501954.
74. Sean J., Song R., Fuemmeler B.F. et al. The biological marker of aging p16ink4a in T cells and the risk of breast cancer. Cancer diseases (Basel). October 26, 2020; 12 (11):3122. doi: 10.3390/ cancers12113122. Error B: Cancers (Basel). January 17, 2021; 13 (2): PMID: 33114473; PMCID: PMC7692397.
75. Sedghizadeh P.P., Billington W.D., Paxton D. et al. Is p16-positive oropharyngeal squamous cell carcinoma associated with favorable prognosis? A systematic review and meta-analysis. Oral Oncol. 2016;54:15-27. Doi:https://doi.org/10.1016/j.oraloncology.2016.01.002.
76. Stukan A.I., Porkhanov V.A., Bodnya V.N. Clinical significance of r16-positive status and high index of proliferative activity in patients with oropharyngeal squamous cell carcinoma. Siberian journal of oncology. 2020;19(2):41-48. https://doi.org/10.21294/1814-4861-2020-19-2-41-48
77. Sung H., Ferley J., Siegel R.L. et al. Global Cancer Statistics 2020: GLOBOCAN estimates of morbidity and mortality worldwide for 36 types of cancer in 185 countries. CA Cancer J Clin. 2021 May; 71(3):209-249. doi:https://doi.org/10.3322/caac.21660. Epub 2021 February 4. PMID: 33538338.
78. Wang H., Zhang Y., Bai W. et al. Feasibility of immunohistochemical p16 staining in the diagnosis of human papillomavirus infection in patients with squamous cell carcinoma of the head and neck: A Systematic Review and Meta-Analysis. Front. Oncol. 2020;10. Doi:https://doi.org/10.3389/fonc.2020.524928.
79. Yap M.L., Allo G., Cuartero J. et al. Prognostic significance of human papilloma virus and p16 expression in patients with vulvar squamous cell carcinoma who received radiotherapy. Clin Oncol (R Coll Radiol). 2018 Apr;30(4):254-261. doi:https://doi.org/10.1016/j.clon.2018.01.011. Epub 2018 Feb 12. PMID: 29449057.
80. Yovanovich D.V., Mitrovich S.L., Milosavlevich M.Z. et al. Breast cancer and p16: role in proliferation, malignant transformation and progression. Healthcare (Basel). September 21, 2021;9 (9):1240. doi:https://doi.org/10.3390/healthcare9091240. PMID: 34575014; PMCID: PMC8468846.
