Recurrent high-grade squamous intraepithelial lesion and early-stage cervical cancer (in situ): predictors, long-term treatment outcomes, and opportunities for treatment and prevention

Cover Page

Cite item

Full Text

Abstract

Background. The incidence of recurrent cervical dysplasia and early-stage cervical cancer varies between 2 % and 34 % depending on risk factors; thus, treatment and prevention strategies should be chosen individually. Constantly high incidence of cervical cancer and its recurrence necessitates improved preventive measures.

Aim. To identify predictors of intracervical recurrence of high-grade squamous intraepithelial lesion (HSIL) and earlystage cervical cancer using multivariate analysis in order to improve treatment strategies for newly diagnosed HSIL patients and patients with recurrent HSIL.

Materials and methods. This retrospective multicenter study included 322 patients newly diagnosed with HSIL (n = 300) and early-stage cervical cancer (n = 22), as well as patients with recurrent HSIL. The study was conducted at E.N. Meshalkin National Medical Research Center, Novosibirsk Regional Clinical Oncology Dispensary, Federal Research and Clinical Center for Specialized Medical Care and Medical Technologies of Federal Biomedical Agency of the Russian Federation, Siberian Center of Oncology and Gynecology “AvisMed” LLC, and “Zdorovye” LLC between 2011 and 2924.

All new patients with HSIL or cervical cancer in situ underwent loop radio-wave excision (conization) of the cervix and endocervical curettage. All patients were followed up after this procedure.

After histological examination patients tested positive for human papillomavirus (HPV) with a high recurrence risk were recommended antiviral therapy. Patients were divided into four groups according to the type of their treatment: 1) radio-wave conization of the cervix alone (control group); 2) radio-wave conization of the cervix in combination with laser photodynamic therapy of the cervix; 3) radio-wave conization of the cervix in combination with HPV quadrivalent vaccine; 4) radio-wave conization of the cervix in combination with Cervicon-DIM therapy. Patients with recurrent HSIL also had immunohistochemical or immunocytochemical assessment of p16 and Ki-67 coexpression.

Conclusion. Our study demonstrated the importance of identifying risk factors for recurrence and assessment of p16 and Ki-67 expression. The most significant risk factors included age over 36 years, positive resection margin, and involvement of endocervical crypts. Combination therapy with cervical conization plus local antiviral therapy with Cervicon-DIM was found to be most effective. Endocervical curettage using an endocervical resector can be used for the early diagnosis of HSIL and early-stage cervical cancer.

About the authors

A. O. Shumeykina

Novosibirsk National Research State University; Federal Research Center for Fundamental and Translational Medicine; Institute of Oncology and Neurosurgery, E. N. Meshalkin National Medical Research Center, Ministry of Health of Russia

Author for correspondence.
Email: nashum99@mail.ru

Anastasiya Olegovna Shumeykina

2 Pirogova St., Novosibirsk 630090

2 Timakova St., Novosibirsk 630060

15 Rechkunovskaya St., Novosibirsk 630055

Russian Federation

A. G. Kedrova

Federal Research and Clinical Center for Specialized Medical Care and Medical Technologies, Federal Biomedical Agency of the Russian Federation

ORCID iD: 0000-0003-1031-9376

28 Orekhovyy Bulvar, Moscow 115682

Russian Federation

E. A. Zhdanova

Novosibirsk National Research State University

2 Pirogova St., Novosibirsk 630090

Russian Federation

A. V. Tarkhov

City Clinical Hospital No. 1 of Novosibirsk Region

6 Zalesskogo St., Novosibirsk 630075

Russian Federation

S. E. Krasilnikov

Novosibirsk National Research State University; Federal Research Center for Fundamental and Translational Medicine

ORCID iD: 0000-0003-0687-0894

2 Pirogova St., Novosibirsk 630090

2 Timakova St., Novosibirsk 630060

Russian Federation

References

  1. Kulkarni A., Covens A., Durand N. et al. Role of HPV in the prediction of persistence/recurrence after treatment for cervical precancer. J Obstet Gynaecol Can 2023;45(10):102171. doi: 10.1016/j.jogc.2023.06.006
  2. Bittencourt D.D., Zanine R.M., Martins Sebastião A.P. et al. Risk factors for persistence or recurrence of high-grade cervical squamous intraepithelial lesions. Rev Col Bras Cir 2023;50:e20233537. doi: 10.1590/0100-6991e-20233537-en
  3. Ikeda M., Mikami M., Yasaka M. et al. Association of menopause, aging and treatment procedures with positive margins after therapeutic cervical conization for CIN 3: A retrospective study of 8,856 patients by the Japan Society of Obstetrics and Gynecology. J Gynecol Oncol 2021;32(5):e68. doi: 10.3802/jgo.2021.32.e68
  4. Andersson S., Megyessi D., Belkić K. et al. Age, margin status, high-risk human papillomavirus and cytology independently predict recurrent high-grade cervical intraepithelial neoplasia up to 6 years after treatment. Oncol Lett 2021;22:684. doi: 10.3892/ol.2021.12945
  5. Zhai F., Mu S., Song Yu. et al. Machine learning prediction of residual and recurrent high-grade CIN post-LEEP. Cancer Manag Res 2024;16:1175–87. doi: 10.2147/CMAR.S484057
  6. Bogani G., DI Donato V., Sopracordevole F. et al. Recurrence rate after loop electrosurgical excision procedure (LEEP) and laser conization: A 5-year follow-up study. Gynecol Oncol 2020;159(3):636–41. doi: 10.1016/j.ygyno.2020.08.025
  7. Giannini A., Di Donato V., Sopracordevole F. et al. Outcomes of high-grade cervical dysplasia with positive margins and HPV persistence after cervical conization. Vaccines (Basel) 2023;11(3):698. doi: 10.3390/vaccines11030698
  8. Ding T., Li L., Duan R. et al. Risk factors analysis of recurrent disease after treatment with a loop electrosurgical excision procedure for high-grade cervical intraepithelial neoplasia. Int J Gynaecol Obstet 2023;160(2):538–47. doi: 10.1002/ijgo.14340
  9. Casajuana-Pérez A., Ramírez-Mena M., Ruipérez-Pacheco E. et al. Effectiveness of prophylactic human papillomavirus vaccine in the prevention of recurrence in women conized for HSIL/ CIN 2–3: The VENUS Study. Vaccines 2022;10:288. doi: 10.3390/vaccines10020288
  10. Abdulaziz A.M.A., You X., Liu L. et al. Management of high-grade squamous intraepithelial lesion patients with positive margin after LEEP conization: A retrospective study. Medicine (Baltimore) 2021;100(20):e26030. doi: 10.1097/MD.0000000000026030
  11. Wang X., Xu J., Gao Y., Qu P. Necessity for subsequent surgery in women of child-bearing age with positive margins after conization. BMC Womens Health 2021;21(1):191. doi: 10.1186/s12905-021-01329-x. Erratum in: BMC Womens Health 2021;21(1):228. doi: 10.1186/s12905-021-01367-5
  12. 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):e12792. doi: 10.1097/MD.0000000000012792
  13. Bogani G., Lalli L., Sopracordevole F. et al. Development of a nomogram predicting the risk of persistence/recurrence of cervical dysplasia. Vaccines (Basel) 2022;10(4):579. doi: 10.3390/vaccines10040579
  14. Mkrtchyan L.S., Kiseleva V.I., Krikunova L.I. et al. Status and molecular genetic parameters of papillomavirus infection: individual characteristics and associations with clinical and morphological factors of cervical cancer. Yuzhno-Rossiyskiy onkologicheskiy zhurnal = South Russian Journal of Cancer 2024;5(2):53–65. (In Russ.). doi: 10.37748/2686-9039-2024-5-2-6
  15. Tanaka M., Yamanoi K., Taki M. et al. High-grade vaginal intraepithelial neoplasia after hysterectomy for high-grade cervical intraepithelial neoplasia: Is hysterectomy a “definitive” treatment compared to conization? J Obstet Gynaecol Res 2023;49(9):2361–9. doi: 10.1111/jog.15723
  16. Banerjee S. Attenuation of multi-targeted proliferation-linked signaling by 3,3’-diindolylmethane (DIM): From bench to clinic. Mutat Res 2011;728:47–66.
  17. Chang X., Tou J., Hong Ch. et al. 3,3’-Diindolylmethane inhibits angiogenesis and the growth of transplantable human breast carcinoma in athymic mice. Carcinogenesis 2005;26(4):771–8.
  18. Maruthanila V.L., Poornima J., Mirunalini S. Attenuation of carcinogenesis and the mechanism underlying by the influence of indole-3-carbinol and its metabolite 3,3’-diindolylmethane: A therapeutic marvel. Adv Pharmacol Sci 2014;2014:832161. doi: 10.1155/2014/832161
  19. Kruglova D.Yu., Tskhay V.B., Savchenko A.A. Efficacy of indole-3-carbinol in comprehensive therapy for HPV-associated cervical pathology in women. Rossiyskiy vestnik akushera-ginekologa = Russian Bulletin of Obstetrician-Gynecologist 2011;11(5):63–6. (In Russ.).
  20. Kiselev V.I. Vaginal suppositories with 3,3’-diindolylmethane (methindole). Patent No. RU2318510C1. Available at: https://patents.google.com/patent/RU2318510C1/ru. (In Russ.).
  21. Adamyan L.V., Makiyan Z.N., Shumeykina A.O., Krasilnikov S.E. Endocervical resector – utility model. Application from 06.12.2024.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c)



СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 36991 от  21.07.2009.