Extended diagnosis of cervical lesions

Aim. To improve the efficiency of diagnosing cervical pathologies using cytology and polymerase chain reaction (PCR) for human papillomavirus (HPV), taking into account the detection of HPV in upper parts of the endocervix.

Materials and methods. The study involved 60 patients with cervical pathology. The results of the cytological studies were verified according to The Bethesda system; the patients were divided into groups based on the results: Group I (n = 22) – negative for intraepithelial lesion or malignancy (NILM), Group II (n = 18) – low-grade squamous intraepithelial lesion (L-SIL), Group III (n = 12) – high-grade squamous intraepithelial lesion (H-SIL), Group IV (n = 8) – atypical squamous cells of undetermined significance (ASC-US). Standard PCR testing for HPV and PCR of the endocervical homogenate were conducted using the Hybrid Capture Digene test (RF Patent No. 2833119 dated December 14, 2023).

Results. Persistence of HPV in the upper endocervix was detected in 45 (75%) of patients. HPV was diagnosed significantly more often (p = 0.0157) in patients with L-SIL and H-SIL cytology – in 89% (16/18) и 100% (12/12) cases, respectively. Oncogenic HPV serotypes were found in 59% (13/22) of patients with NILM and in 50% (4/8) of patients with ASC-US. High frequency of discrepancies in the profile of the detected HPV strains between standard PCR and homogenate PCR testing was observed and was comparable across all groups: NILM 64% (14/22); L-SIL 61% (11/18); H-SIL 58% (7/12); ASC-US 75% (6/8), p > 0,05. Persistence of HPV in the upper parts of the cervix with negative standard PCR results was detected in 41% (9/22) of patients with NILM. A high viral load in the homogenate was detected more frequently in patients of the H-SIL group (p = 0.0374).

Conclusion. Extended diagnosis allows for a comprehensive assessment of the degree of cervical involvement in the pathology and helps determine the optimal management strategy for women at high risk (H-SIL, recurrent L-SIL, HPV persistence with high viral load).

1. Zhang Y., Qiu K., Ren J., Zhao Y., Cheng P. Roles of human papillomavirus in cancers: oncogenic mechanisms and clinical use. Signal Transduct. Target. Ther. 2025;10(1):44. DOI: 10.1038/s41392-024-02083-w.

2. Global strategy to accelerate the elimination of cervical cancer as a public health problem. Geneva: World Health Organization; 2020. Licence: CC BY-NC-SA 3.0 IGO.

3. Кондриков Н.И., Баринова И.В. Патология матки. Руководство для врачей; 2-е изд. М.: Практическая медицина, 2019:352.

4. Chen J.Y., Wang Z.L., Wang Z.Y., Yang X.S. The risk factors of residual lesions and recurrence of the high-grade cervical intraepithelial lesions (HSIL) patients with positive-margin after conization. Medicine (Baltimore). 2018;97(41):12792. DOI: 10.1097/MD.0000000000012792.

5. Rayner M., Welp A., Stoler M.H., Cantrell L.A. Cervical cancer screening recommendations: Now and for the Future. Healthcare (Basel). 2023;11(16):2273. DOI: 10.3390/healthcare11162273.

6. Feng T., Cheng B., Sun W., Yang Y. Outcome and associated factors of high-risk human papillomavirus infection without cervical lesions. BMC Womens Health. 2023;23(1):599. DOI: 10.1186/s12905-023-02764-8.

7. Adebamowo S.N., Befano B., Cheung L.C., Rodriguez A.C., Demarco M., Rydzak G. et al. Different human papillomavirus types share early natural history transitions in immunocompetent women. Int. J. Cancer. 2022;151(6):920–929. DOI: 10.1002/ijc.34128.

8. Louvanto K., Syrjänen K.J., Rintala M.A., Grénman S.E., Syrjänen S.M. Genotype-specific clearance of genital human papillomavirus (HPV) infections among mothers in the Finnish family HPV study. J. Clin. Microbiol. 2010;48(8):2665–2671. DOI: 10.1128/JCM.00783-10.

9. Curry S.J., Krist A.H., Owens D.K., Barry M.J., Caughey A.B. et al. Screening for Cervical Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;320(7):674–686. DOI: 10.1001/jama.2018.10897.

10. Feldstein O., Gali-Zamir H., Schejter E., Feinberg T., Yehuda-Shnaidman E., Bornstein J. et al. High-risk HPV testing vs liquid-based cytology for cervical cancer screening among 25- to 30-year-old women: A historical cohort study. Acta. Obstet. Gynecol. Scand. 2023;102(2):226–233. DOI: 10.1111/aogs.14482. Epub 2022 Dec 7.

11. WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention, second edition. Geneva: World Health Organization; 2021. Licence: CC BY-NC-SA 3.0 IGO.

12. Tai Y.J., Chen Y.Y., Hsu H.C., Chiang C.J., You S.L., Chen H.C. et al. Taiwan Cervical Cancer Control Task Force. Clinical management and risk reduction in women with lowgrade squamous intraepithelial lesion cytology: A population-based cohort study. PLoS One. 2017;12(12):e0188203. DOI: 10.1371/journal.pone.0188203.

13. Buick C., Jembere N., Wang L., Kupets R. Cervical screening and colposcopy management of women age 24 and under. J. Obstet. Gynaecol. Can. 2020;42(12):1518–1524. DOI: 10.1016/j.jogc.2020.06.013.

14. Min C.J., Massad L.S., Dick R., Powell M.A., Kuroki L.M. Assessing physician adherence to guidelines for cervical cancer screening and management of abnormal screening results. J. Low. Genit. Tract. Dis. 2020;24(4):337–342. DOI: 10.1097/LGT.0000000000000558.

15. Malagón T., Volesky K.D., Bouten S., Laprise C., El-Zein M., Franco E.L. Cumulative risk of cervical intraepithelial neoplasia for women with normal cytology but positive for human papillomavirus: Systematic review and meta-analysis. Int. J. Cancer. 2020;147(10):2695–2707. DOI: 10.1002/ijc.33035.

16. Kang W.D., Ju U.C., Kim S.M. Human papillomavirus genotyping for predicting disease progression in women with biopsy-negative or cervical intraepithelial neoplasia grade 1 of low-grade intraepithelial lesion cytology. Int. J. Gynecol. Cancer. 2024;34(1):12–18. DOI: 10.1136/ijgc2023-004902.

17. Firnhaber C., Swarts A., Goeieman B., Rakhombe N., Mulongo M., Williamson A.L. et al. Cryotherapy Reduces Progression of Cervical Intraepithelial Neoplasia Grade 1 in South African HIV-Infected Women: A Randomized, Controlled Trial. J. Acquir. Immune. Defic. Syndr. 2017;76(5):532–538. DOI: 10.1097/QAI.0000000000001539.

18. Zhou D., Xue J., Sun Y., Zhu L., Zhao M., Cui M. et al. Patterns of single and multiple HPV infections in female: A systematic review and meta-analysis. Heliyon. 2024;10(17):e35736. DOI: 10.1016/j.heliyon.2024.e35736.

19. Tao X., Zhang H., Zhang H., Xiao Y., Zhong F., Zhou X. et al. The clinical utility of extended high-risk HPV genotyping in risk-stratifying women with L-SIL cytology: A retrospective study of 8726 cases. Cancer Cytopathol. 2022;130(7):542– 550. DOI: 10.1002/cncy.22573.

20. Ni X., Hu J., Huang Y., Tao J., Zhu H. Higher clearance rates of multiple HPV infections may explain their lower risk of HSIL: A retrospective study in Wenzhou, China. J. Med. Virol. 2023;95(2):e28526. DOI: 10.1002/jmv.28526. PMID: 36698241.

21. Zhang Y., Ni Z., Wei T., Liu Q. Persistent HPV infection after conization of cervical intraepithelial neoplasia - a systematic review and meta-analysis. BMC Womens Health. 2023;23(1):216. DOI: 10.1186/s12905-023-02360-w.