Diagnostic sensitivity and specificity complex in women with intraepithelial lesions of the cervix utery
DOI:
https://doi.org/10.15574/HW.2024.4(173).2125Keywords:
intraepithelial lesions of the cervix, diagnosis, liquid cytology, immunocytochemical method, oncoprotein p16ink4α, proliferation marker Ki67Abstract
Aim - study the molecular and biological features of cervical intraepithelial lesions (SIL) using the immunocytochemical method of determining the oncoprotein p16ink4α and the proliferation marker Ki67 in order to further develop a highly effective method for the early diagnosis cervical cancer.
Materials and methods. Examined 150 women with a histologically verified diagnosis of SIL, of which the group 1 - 74 women with low-grade squamous intraepithelial lesion of the uterine cervix (LSIL) and the group 2 - 76 women with high-grade squamous intraepithelial lesion of the uterine cervix (HSIL). The control group included 70 women without morphological changes negative for cervical intraepithelial lesion (NILM). The average age of the patients is 32.7±0.5 years. Liquid cytology was taken from all patients and an immunocytochemical method (ICH) was performed to determine the expression of the oncoprotein p16ink4α and the proliferation marker Ki67 and complex genotyping of HPV DNA of 28 types. Statistical processing of research results was carried out using standard Microsoft Excel 5.0 and Statistical 6.0 programs.
Results. The expression of the oncoprotein p16ink4α in patients of the group 1 (LSIL) was 27.2% of atypical squamous cells in the smear, the proliferation marker Ki67 was 11.6%. In women of the group 2 (HSIL), expression of oncoprotein p16ink4α - 58.9%, proliferation marker Ki67 - 30.7%. In patients of the control group (NILM), individual p16ink4α - positive cells were found in 0.72%, while they lacked the expression of the proliferation marker Ki67, which allowed to classify them as "senescent" cells. For p16ink4α, diagnostic sensitivity was 97.4%, diagnostic specificity was 76.8%. For the proliferation marker Ki67, diagnostic sensitivity was 100%, diagnostic specificity was 92.8%.
Conclusions. The most informative method for detecting SIL is p16ink4α/Ki67 coexpression: diagnostic sensitivity - 98.5%, specificity - 100% compared to liquid cytology and HPV test.
The research was conducted according to principles of Declaration of Helsinki. Protocol of research was proved by local ethical committee, mentioned in institution’s work. A informed sonsennt was collected in order to carry out the research.
The author is stating no conflict of interests is declared.
References
Avian A, Clemente N, Mauro E, Isidoro E, Di Napoli M, Dudine S et al. (2022, May 17). Clinical validation of full HR-HPV genotyping HPV Selfy assay according to the international guidelines for HPV test requirements for cervical cancer screening on clinician-collected and self-collected samples. J Transl Med. 20(1): 231. doi: 10.1186/s12967-022-03383-x. Erratum in: J Transl Med. 2023 Jan 26;21(1):49. PMID: 35581584; PMCID: PMC9115952. https://doi.org/10.1186/s12967-023-03882-5
Bhatla N, Singhal S. (2020, May). Primary HPV screening for cervical cancer. Best Pract Res Clin Obstet Gynaecol. 65: 98-108. Epub 2020 Mar 2. PMID: 32291178. https://doi.org/10.1016/j.bpobgyn.2020.02.008
Chiou PZ. (2023). HPV Primary and Co-testing: An Ethical Analysis Exploring the Role of Cytology in Cervical Cancer Screening and Management. J Allied Health. 52(4): 301-304. PMID: 38036477.
Dovnik A, Repše Fokter A. (2023, Oct 19). The Role of p16/Ki67 Dual Staining in Cervical Cancer Screening. Curr Issues Mol Biol. 45(10): 8476-8491. PMID: 37886977; PMCID: PMC10605736. https://doi.org/10.3390/cimb45100534
Elfström KM, Eklund C, Lamin H, Öhman D, Hortlund M, Elfgren K et al. (2021, Aug 23). Organized primary human papillomavirus-based cervical screening: A randomized healthcare policy trial. PLoS Med. 18(8): e1003748. PMID: 34424907; PMCID: PMC8423359. https://doi.org/10.1371/journal.pmed.1003748
Fontham ETH, Wolf AMD, Church TR, Etzioni R, Flowers CR, Herzig A et al. (2020, Sep). Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society. CA Cancer J Clin. 70(5): 321-346. Epub 2020 Jul 30. PMID: 32729638. https://doi.org/10.3322/caac.21628
Gavinski K, Di Nardo D. (2023, Mar). Cervical Cancer Screening. Med Clin North Am. 107(2): 259-269. Epub 2022 Dec 26. PMID: 36759096. https://doi.org/10.1016/j.mcna.2022.10.006
Giorgi Rossi P, Carozzi F, Ronco G, Allia E, Bisanzi S, Gillio-Tos A et al. (2021, Mar 1). p16/ki67 and E6/E7 mRNA Accuracy and Prognostic Value in Triaging HPV DNA-Positive Women. J Natl Cancer Inst. 113(3): 292-300. doi: 10.1093/jnci/djaa105. Erratum in: J Natl Cancer Inst. 2022 Feb 7; 114(2): 324. PMID: 32745170; PMCID: PMC7936054. https://doi.org/10.1093/jnci/djab107
Hammer A, Gravitt P. (2021, Mar). Clinical implications of transitioning from cytology to human papillomavirus-based cervical cancer screening. Acta Obstet Gynecol Scand. 100(3): 371-372. PMID: 33739440. https://doi.org/10.1111/aogs.14107
Jeromel S, Repše Fokter A, Dovnik A. (2024, Apr 23). P16/Ki67 Dual Staining in Glandular Cell Abnormalities of the Uterine Cervix. Cancers (Basel). 16(9): 1621. PMID: 38730573; PMCID: PMC11083027. https://doi.org/10.3390/cancers16091621
Liu J, Su S, Liu Y. (2022, May 9). The value of Ki67 for the diagnosis of LSIL and the problems of p16 in the diagnosis of HSIL. Sci Rep. 12(1): 7613. PMID: 35534530; PMCID: PMC9085733. https://doi.org/10.1038/s41598-022-11584-z
Mazurec K, Trzeszcz M, Mazurec M, Streb J, Halon A, Jach R. (2023, Oct 21). Triage Strategies for Non-16/Non-18 HPV-Positive Women in Primary HPV-Based Cervical Cancer Screening: p16/Ki67 Dual Stain vs. Cytology. Cancers (Basel). 15(20): 5095. PMID: 37894462; PMCID: PMC10605570. https://doi.org/10.3390/cancers15205095
Mintser AP. (2018). Statisticheskie metodyi issledovaniya v klinicheskoy meditsine. Prakticheskaya meditsina. 3: 41-45.
Moiseienko RO, Zhylka NIa, Hoida NH, Dudina OO, Holubchykov MV, Oktysiuk ZhS. (2023). Stan reproduktyvnoho zdorovia zhinok Ukrainy. Ukraina. Zdorovia natsii. (1): 51-59. https://doi.org/10.32782/2077-6594/2023.1/09
Patarapadungkit N, Khonhan P, Pisuttimarn P, Pientong C, Ekalaksananan T, Koonmee S. (2020, Jul 1). Human Papillomavirus Detection and Abnormal Anal Cytology in HIV-infected Patients Using p16/Ki-67 Dual-Staining. Asian Pac J Cancer Prev. 21(7): 2013-2019. PMID: 32711427; PMCID: PMC7573428. https://doi.org/10.31557/APJCP.2020.21.7.2013
Pimple SA, Mishra GA, Deodhar KK. (2020, Apr). Evidence based appropriate triage strategies for implementing high risk HPV as primary technology in cervical cancer screening. Minerva Ginecol. 72(2): 96-105. PMID: 32403908. https://doi.org/10.23736/S0026-4784.20.04511-6
Rajaram S, Gupta B. (2021, Aug). Screening for cervical cancer: Choices & dilemmas. Indian J Med Res. 154(2): 210-220. PMID: 34854432; PMCID: PMC9131755. https://doi.org/10.4103/ijmr.IJMR_857_20
Staats PN, Davey DD, Witt BL, Ghofrani M, Zhao C, Dodd LG et al. (2022, Mar-Apr). Performance of specific morphologic features in distinguishing low-grade squamous intraepithelial lesions from high-grade squamous intraepithelial lesions in borderline cases: a College of American Pathologists Cytopathology Committee multiobserver study. J Am Soc Cytopathol. 11(2): 102-113. Epub 2021 Nov 10. PMID: 34903496. https://doi.org/10.1016/j.jasc.2021.11.001
Tantitamit T, Khemapech N, Havanond P, Termrungruanglert W. (2020, Jan-Dec). Cost-Effectiveness of Primary HPV Screening Strategies and Triage with Cytology or Dual Stain for Cervical Cancer. Cancer Control. 27(1): 1073274820922540. PMID: 32372659; PMCID: PMC7218320. https://doi.org/10.1177/1073274820922540
Wentzensen N, Clarke MA. (2021, Mar). Cervical Cancer Screening-Past, Present, and Future. Cancer Epidemiol Biomarkers Prev. 30(3): 432-434. PMID: 33857013. https://doi.org/10.1158/1055-9965.EPI-20-1628
Xiao T, Wang C, Yang M, Yang J, Xu X, Shen L et al. (2023, Aug 1). Use of Virus Genotypes in Machine Learning Diagnostic Prediction Models for Cervical Cancer in Women With High-Risk Human Papillomavirus Infection. JAMA Netw Open. 6(8): e2326890. PMID: 37531108; PMCID: PMC10398410. https://doi.org/10.1001/jamanetworkopen.2023.26890
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Ukrainian Journal Health of Woman
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The policy of the Journal UKRAINIAN JOURNAL «HEALTH OF WOMAN» is compatible with the vast majority of funders' of open access and self-archiving policies. The journal provides immediate open access route being convinced that everyone – not only scientists - can benefit from research results, and publishes articles exclusively under open access distribution, with a Creative Commons Attribution-Noncommercial 4.0 international license (СС BY-NC).
Authors transfer the copyright to the Journal UKRAINIAN JOURNAL «HEALTH OF WOMAN» when the manuscript is accepted for publication. Authors declare that this manuscript has not been published nor is under simultaneous consideration for publication elsewhere. After publication, the articles become freely available on-line to the public.
Readers have the right to use, distribute, and reproduce articles in any medium, provided the articles and the journal are properly cited.
The use of published materials for commercial purposes is strongly prohibited.