The role of immunocytochemical biomarkers in diagnostics of precancerous pathology of cervix

I.Z. Gladchuk; N.M. Rozhkovska; N.M.  Kashtalian

doi:10.26641/2307-0404.2021.2.234521

Авторы

I.Z. Gladchuk Odessa National Medical University, Department of Obstetrics and Gynecology, Valikhovskiy lane, 2, Odessa, 65026, Ukraine, Ukraine https://orcid.org/0000-0003-2926-4125
N.M. Rozhkovska Odessa National Medical University, Department of Obstetrics and Gynecology, Valikhovskiy lane, 2, Odessa, 65026, Ukraine, Ukraine https://orcid.org/0000-0001-7860-3272
N.M. Kashtalian Odessa National Medical University, Department of Obstetrics and Gynecology, Valikhovskiy lane, 2, Odessa, 65026, Ukraine, Ukraine https://orcid.org/0000-0003-1386-3668

DOI:

https://doi.org/10.26641/2307-0404.2021.2.234521

Ключевые слова:

cervical dysplasia, cervical intraepithelial neoplasia, diagnostics, immunocytochemistry, biomarkers, p16, Ki-67

Аннотация

The last decades showed the worldwide tendency to finding consensus between diagnostics improvement and constant increase of cost of medical services in conditions of restricted financing. The aim of the article was to analyze the diagnostic value of p16 and Ki-67 biomarkers in diagnostics of precancerous diseases of cervix. Data of 80 patients with cervical dysplasia of varying degree who received excisional treatment were analyzed. It was shown that cytological study has a high sensitivity (79.17%) for the diagnosis of CIN 2-3, but low specificity (53.57%). The p16 immunocytochemical biomarker has a high sensitivity for the diagnosis of CIN 2 (0.92; 95% CI: 0.76-0.98) with good specificity (0.78; 95% CI: 0.67-0.82), for the diagnosis of CIN 3 both sensitivity (0.93; 95% CI: 0.82-0.98) and specificity (0.93; 95% CI: 0.82-0.98) is high. The immunocytochemical biomarker Ki-67 has a high sensitivity for CIN 2 (0.92; 95% CI: 0.65-0.99), but insufficient specificity (0.62; 95% CI: 0.54-0.64), for the diagnosis of CIN 3 the sensitivity is very high (0.96; 95% CI: 0.80-0.99) as well as specificity (0.78; 95% CI: 0.69-0.81). The combined use of p16 and Ki-67 biomarkers can significantly increase the diagnostic accuracy of the diagnosis of high-grade precancerous pathology of cervix and justify timely surgical intervention. Such an approach for the differential diagnosis of severe dysplasia, on the one hand, may contribute to a decrease in the risk of developing cervical cancer, and on the other hand, it will allow to avoid unnecessary operations and preserve reproductive function of women, reduce the economic costs of treatment.

Библиографические ссылки

Antomonov M. [Mathematical processing and analysis of biomedical data]. 2nd ed. Kyiv: MIC «Medinform». 2018. p. 579. Russian. ISBN 978-966-409-202-6

Hnatko OP, Skuriatina NH, Berezhna TA. [Diagnostic value of markers of proliferation in determination of the degree of severity of cervical precancerous lesions]. Aktalni pytannia pediatrii, akusherstva ta hinekologii. 2018;1:56-61. Ukrainian. Available from: https://ojs.tdmu.edu.ua/index.php/act-pit-pediatr/article/view/8736

Zaporozhan VM, et al. [National consensus in management of patients with cervical intraepithelial neoplasia caused by papillomaviral infection]. Zdorovia zhinky. 2017;123(7):16-24. Ukrainian. Available from: https://ecopharm.ua/wp-content/uploads/2016/10/ZZH-7_Consensus-2.pdf

Singer A, Khan A. [Cervical and lower genital tract precancer: diagnosis and treatment]. Moskow: HEOTAR-Media; 2017. p. 312 Russian. ISBN: 978-5-9704-4296-8

Tumanskii VA, Pyrohova ZA. [Specifics of Ki-67, p16ink4a, HPV16v immune histochemical expression in cervical intraepithelial neoplasia and cervical carcino¬ma]. Patolohiia. 2017;14(2):202-8. Ukrainian. Available from: http://pat.zsmu.edu.ua/article/view/109298

Chen CC, Huang LW, Bai CH, Lee CC. Predictive value of p16/Ki-67 immunocytochemistry for triage of women with abnormal Papanicolaou test in cervical cancer screening: a systematic review and meta-analysis. Annals of Saudi medicine. 2016;36(4):245-1. doi: https://doi.org/10.5144/0256-4947.2016.245

Khazaei S, Izadi B, Mirbahari SG, et al. Compa¬rison Between Two Detection Methods for HPV16, HPV18 and P16Ink4a Biomarkers in Diagnosis of Abnor¬mal Cervical Cytology. Asian Pac J Cancer Prev. 2016;17(12):5223-7. Published 2016 Dec 1. doi: https://doi.org/10.22034/APJCP.2016.17.12.5223

Zhang L, Dai Y, Chen J, et al. Comparison of the performance in detection of HPV infections between the high-risk HPV genotyping real time PCR and the PCR-reverse dot blot assays. J Med Virol. 2018;90(1):177-83. doi: https://doi.org/10.1002/jmv.24931

Rozemeijer K, Penning C, Siebers AG, Naber SK, Matthijsse SM, van Ballegooijen M, van Kemenade FJ, de Kok IM. Comparing SurePath, ThinPrep, and con¬ventional cytology as primary test method: SurePath is associated with increased CIN II+ detection rates. Cancer causes & control: CCC. 2016;27(1):15-25. doi: https://doi.org/10.1007/s10552-015-0678-1

Kyrgiou M, Kalliala IEJ, Mitra A, Fotopoulou C, Ghaem‐Maghami S, Martin‐Hirsch PPL, Cruickshank M, Arbyn M, Paraskevaidis E. Immediate referral to colposcopy versus cytological surveillance for minor cervical cytological abnormalities in the absence of HPV test. Cochrane Database of Systematic Reviews 2017;1:CD009836. doi: https://doi.org/10.1002/14651858.CD009836.pub2

Kyrgiou M, Athanasiou A, Kalliala IEJ, et al. Obstetric outcomes after conservative treatment for cervical intraepithelial lesions and early invasive disease. Cochrane Database Syst Rev. 2017;11(11):CD012847. Published 2017 Nov 2. doi: https://doi.org/10.1002/14651858.CD012847

Das D, Sengupta M, Basu K, Tirkey M, Datta C, Chatterjee U. Role of p16/Ki-67 Dual Immunostaining in Detection of Cervical Cancer Precursors. J Cytol. 2018;35(3):153-8. doi: https://doi.org/10.4103/JOC.JOC_4_17

Verma L, Shamsunder S, Malik S, Arora R. To Evaluate the Role of p16Ink4a Immunocytochemistry for Detection of CIN2+ in Women Detected Screen Posi¬tive by Visual Inspection Using Acetic Acid. J Cytol. 2020;37(2):82-86. doi: https://doi.org/10.4103/JOC.JOC_89_18

Ziemke P, Griesser H. p16-/Ki-67 in der Zervix-Zytologie: Indikationen [Indications for p16/Ki-67 in cervical cytology]. Pathologe. 2017;38(1):38-44. doi: https://doi.org/10.1007/s00292-016-0262-9