Directions for Improving the Laboratory Component in Secondary Prevention of Cervical Cancer

Relevance. Effective responses are required due to the high incidence of cervical cancer (Cc) throughout the World. RT-PCRbased HPV-testing is becoming more prominent in secondary prevention worldwide, replacing cytology. Russian practice still relies on cytology as the primary method mainly because there is a lack of comparative evaluation of the diagnostic characteristics of cytology and HPV-tests. Aim. Evaluation of diagnostic characteristics of laboratory methods and the relevance of extended HPV genotyping for secondary prevention of cervical cancer. Materials & methods. The study included data (liquid cytology, histology, HPV-test results) from a survey of 653 women (M = 33.55 years old, ME = 32.0 years old, IQR: 26-38 years old) infected with 14 HPV types (16, 18, 31, 33, 35, 39, 45, 45, 51, 52, 56, 58, 59, 66, 68), with presence or absence of intraepithelial neoplasia of varying severity. The study analyzed the correlation of cervical cytology - histology, clinical sensitivity for high-grade squamous intraepithelial lesions (HSIL+), the incidence and the role of 14 oncogenic HPV types in the development of cervical intraepithelial pathology, positive predictive value (PPV) and the diagnostic accuracy of the HPV-test. Results. The agreement between cytology and histology is 67.20%. Clinical sensitivity of cytology is 83.78% for HSIL+ and 94.34% for any other than NILM result. The structure of the HPV population varies depending on the degree of neoplasia, with a constant predominance of HPV16. The clinical sensitivity of the laboratory component rises to 99.5% by conducting HPV-test for at least 12 types of virus. HSIL is more commonly associated with viruses of alpha-9 phylogenetic group, than with alpha-7 and alpha-5/6. The positive predictive value for HSIL+ is reduced depending on the HPV type: 16>33>58>35>45>31>18>52>39>59>58>56>68>66. Conclusions. Clinical sensitivity of the HPV-test exceeds that of cytology, so that secondary prevention of cervical cancer can be effectively achieved through HPV testing. The introduction of an extended genotyping provides more complete information about the risk of having HSIL+. The data obtained will form the basis for the development of directions for improving the epidemiological surveillance information subsystem of HPVassociated cervical diseases

1. Tservikalnaja intraepitelialnaja neoplasia, erosia i ektropion shejki matki. Klinicheskie rekomendatsii. Tservikalnaja intraepitelialnaja neoplasia, erosia i ektropion shejki matki. Klinicheskie rekomendatsii. 2020. Available at: https:.cr.minzdrav.gov.ru/recomend/597_1. Accessed: 22 February 2024. (In Russ.).

2. Sushinskaya TV, Volchenko NN, Dobrohotova EE, et al. Effectiveness of cytological diagnosis of cervical epithelial neoplasia and cervical cancer based on the tissue sampling method. Onkogynecologija.2017; 3:51–59 (In Russ.).

3. Tritz DM, Weeks JA, Spires SE, et al. Etiologies for non-correlating cervical cytologies and biopsies. Am J Clin Pathol. 1995;103(5):594 –597. doi:10.1093/ajcp/103.5.594

4. Tzeng JE, Chen JT, Chang MC, Ho WL. Discordance between uterine cervical cytology and biopsy: results and etiologies of a one-year audit. Kaohsiung J Med Sci. 1999;15(1):26 –31.

5. Meijer, Chris J L M et al. Guidelines for human papillomavirus DNA test requirements for primary cervical cancer screening in women 30 years and older. International journal of cancer .2009;124(3): 516 –20. doi:10.1002/ijc.24010

6. Domonova E.A., Popova A.A., Kuleshova O.B., et al. Raspostranennost virusa papillomi cheloveka razlichnogo kantserogennogo riska sredi naselenija Moskovskogo regiona. Svidetelstvo o registratsii bazi dannih №2022621655. 07.07.2022. (In Russ.).

7. Domonova EA, Tvorogova MG, Podkolzin AT, et al. Vzatije, transportirovka, hranenije klinicheskogo materiala dlia PCR-diagnostiki. Metodicheskie rekomemdatsii. Moscow: Tsentralnij nauchno-issledovatelskij institut epidemiologii 2021. (In Russ.). doi: https://doi.org/10.36233/978-5-6045286-6-2 Available at: https:.interlabservice.ru/consulting/adv/files/transporting_store.pdf/. Accessed: 22 February 2024. (In Russ.).

8. Kuleshova OB, Domonova EA, Romanuk TN, et al. Practical aspects of the implementation of screening for the detection of malignant neoplasms of the cervix during the medical examination of certain groups of the adult population Epidemiology and Vaccinal Prevention. 2023;22(4):75 –85. (In Russ.). https://doi:10.31631/2073-3046-2023-22-4-75-85

9. Barinova IV, Khan SO, Voloschuk IN, et al. Sopostavlenije rezultatov gistologicheskogo b tsitologicheskogo issledovanij pri patologii shejki matki. Vzgliad patologoanatoma. Russian News of Clinical Cytology. 2020;24(4):26 –30. (In Russ.). doi: 10.24412/1562-4943-2020-4-0005

10. Asaturova A, Dobrovolskaya D, Magnaeva A, et al. Cervical Cytology-Histology Correlation Based on the American Society of Cytopathology Guideline (2017) at the Russian National Medical Research Center for Obstetrics, Gynecology, and Perinatology. Diagnostics (Basel). 2022; 12(1):210. doi:10.3390/diagnostics12010210

11. Attoeva DI, Asaturova AV, Nazarova NM, et al. Comparison of the results of clinical and morphological methods of research in HPV-associated diseases of the cervics (retrospective study). Gynecology. 2021;23(1):78 –82. (In Russ.). DOI: 10.26442/20795696.2021.1.200647

12. Joste NE, Crum CP, Cibas ES. Cytologic/histologic correlation for quality control in cervicovaginal cytology. Experience with 1,582 paired cases. Am J Clin Pathol. 1995;103(1):32 –34. doi:10.1093/ajcp/103.1.32

13. Gupta R, Hariprasad R, Dhanasekaran K, et al. Reappraisal of cytology-histology correlation in cervical cytology based on the recent American Society of Cytopathology guidelines (2017) at a cancer research centre. Cytopathology. 2020;31(1):53 –58. doi:10.1111/cyt.12774

14. Koliopoulos G, Nyaga VN, Santesso N, et al. Cytology versus HPV testing for cervical cancer screening in the general population. Cochrane Database Syst Rev. 2017;8(8):CD008587. doi:10.1002/14651858.CD008587.pub2

15. Bruni L, Serrano B, Roura E, et al. Cervical cancer screening programmes and age-specific coverage estimates for 202 countries and territories worldwide: a review and synthetic analysis [published correction appears in Lancet Glob Health. 2023 Jul;11(7):e1011]. Lancet Glob Health. 2022;10(8):e1115-e1127. doi:10.1016/S2214-109X(22)00241-8

16. Adcock R, Cuzick J, Hunt WC, et al.; New Mexico HPV Pap Registry Steering Committee; Role of HPV Genotype, Multiple Infections, and Viral Load on the Risk of High-Grade Cervical Neoplasia. Cancer Epidemiol Biomarkers Prev. 2019;28(11):1816 –1824. doi:10.1158/1055-9965.EPI-19-0239

17. de Sanjose S, Quint WG, Alemany L, et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010;11(11):1048 –1056. doi:10.1016/S1470-2045(10)70230-8

18. Combes JD, Guan P, Franceschi S, et al. Judging the carcinogenicity of rare human papillomavirus types. Int J Cancer. 2015;136(3):740 –742. doi:10.1002/ijc.29019

19. Perkins RB, Guido RS, Castle PE, et al. 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors. J Low Genit Tract Dis. 2020;24(2):102 –131. doi:10.1097/LGT.0000000000000525

20. Bosch FX, Burchell AN, Schiffman M, et al. Epidemiology and natural history of human papillomavirus infections and type-specific implications in cervical neoplasia. Vaccine. 2008;26 Suppl 10:K1-K16. doi:10.1016/j.vaccine.2008.05.064

21. Guan P, Howell-Jones R, Li N, et al. Human papillomavirus types in 115,789 HPV-positive women: a meta-analysis from cervical infection to cancer. Int J Cancer. 2012;131(10):2349 –2359. doi:10.1002/ijc.27485

22. Mkrtchian LS, Kaprin AD, Ivanov SA, et al. Rasprostranennost’ virusa papillomi cheloveka visokogo kantserogennogo riska pri neoplasticheskih patologijah shejki matki. Radiatsija i risk.2018; 27(3):55 –64. (In Russ.). DOI: 10.21870/0131-3878-2018-27-3-55-64

23. Smolyakova RM, Matylevich OP, Gutkovskaya EA, et al. Molecular-genetic diagnostics of human papillomavirus under dysplasia and cervical carcinoma. Health and Ecology issues. 2010. Suppl1(23):52 –54. (In Russ.).

24. Viazovaia AA, Kuevda DA, Trofimova OB, et al. The identification of viruses of human papilloma of high carcinogenic risk and evaluation of physical status of viral DNA using technique of polymerase-chain reaction under affection of cervical epithelium. Klin Lab Diagn. 2013 Aug:(8):24–6. (In Russ.).

25. Brusnigina NF, Makhova MA, Chernevskaya OM, et al. Detection rates of human papillomavirus associated with cervical cancer in women of Nyzhny Novgorod. Public Health and Life Environment – PH&LE.2020;3(324):44 –47. (In Russ.). DOI: http://doi.org/10.35627/2219-5238/2020-324-3-44-47.

26. Dolgushina VF, Abramovskikh OS. Rasprostranennost’ razlichnikh genotipov virusa papilloma cheloveka pri patologii shejki matki. Akusherstvo I ginekologija. 2011;4:69 –74. (In Russ.).

27. Cuzick J, Ho L, Terry G, et al. Individual detection of 14 high risk human papilloma virus genotypes by the PapType test for the prediction of high grade cervical lesions. J Clin Virol. 2014;60(1):44-49. doi:10.1016/j.jcv.2014.02.002

28. Franceschi S, Clifford GM. Re: A study of the impact of adding HPV types to cervical cancer screening and triage tests. J Natl Cancer Inst. 2005;97(12):938 –941. doi:10.1093/jnci/dji159

29. Nakamura Y, Matsumoto K, Satoh T, et al. HPV genotyping for triage of women with abnormal cervical cancer screening results: a multicenter prospective study. Int J Clin Oncol. 2015;20(5):974–981. doi:10.1007/s10147-015-0789-4

30. Tao X, Austin RM, Yu T, et al. Risk stratification for cervical neoplasia using extended high-risk HPV genotyping in women with ASC-US cytology: A large retrospective study from China. Cancer Cytopathol. 2022;130(4):248–258. doi:10.1002/cncy.22536

31. Martinelli M, Giubbi C, Saderi L, et al. Evaluation of Human Papilloma Virus (HPV) Genotyping and Viral Load Determination as Diagnostic Biomarkers of Cervical Cancer Risk. International Journal of Molecular Sciences. 2023; 24(2):1320. https://doi.org/10.3390/ijms24021320

32. Nazarova NM, Burmenskaja OV, Sulamadze LA, et al. Rasprostranennost’ tipov virusa papillomi cheloveka anogenital’noj oblasti u patsientok s VPCHassotsiirovannimi zabolevanijami shejki matki. Akusherstvo i ginekologija.2015;12. 89–96. (In Russ.).