Recurrence of cervical intraepithelial neoplasia: modern view on the problem

DOI

https://dx.doi.org/10.18565/aig.2024.4

Klinyshkova T.V., Buyan M.S., Samosudova I.B.
1) Omsk State Medical University, Ministry of Health of Russia, Omsk, Russia; 2) Gynecological Hospital, Omsk, Russia; 3) Clinical Diagnostic Center "Ultramed", Omsk, Russia

Despite the high effectiveness of excision treatment in patients with CIN 2+, there is an increased risk of cervical cancer in patients who underwent treatment. An increased risk of cervical cancer is associated with the recurrence of precancerous lesions, which reaches 14.4%. A number of scientific studies have proven that a woman’s age, CIN at resection margins, positive HPV test, and abnormal cytology after treatment are predictors of the CIN recurrence. Given the correlation of the persistence of high-risk human papillomavirus (HPV) after conization with the risk of recurrence, it is necessary to repeat a negative HPV test in the dynamics of observation. It was possible to identify the independent risk factors for the persistence/recurrence of CIN using the assessment of the status of the CIN excision margins. These factors are a positive endocervical margin or both resection margins in comparison with the ectocervical margin. The combination of a positive resection margin and persistence of HPV type 16 significantly increases the risk of the persistence/recurrence of CIN 2+. A negative co-test after conization in the dynamics of observation contributes to a favorable prognosis. In order to prevent the recurrence, it is proposed to use a preventive HPV vaccine after excision treatment of CIN that can reduce the development of the CIN 2+ recurrence. The results of the studies show to date that it is necessary to continue the search for optimization of vaccination.
Conclusion: A multi-stage comprehensive approach, which includes the detection of cervical papillomavirus infection after excision treatment of CIN, assessment of the radicality of resection, as well as the subsequent active monitoring, makes it possible to prevent the recurrence and progression of precancerous lesions of the cervix.

Authors’ contributions: Klinyshkova T.V. – developing the concept and design of the study, editing the article; Buyan M.S., Samosudova I.B. – searching and analyzing the material; Klinyshkova T.V., Buyan M.S. – writing the text.
Conflicts of interest: The authors declare no possible conflicts of interest.
Funding: The study was conducted without sponsorship.
For citation: Klinyshkova T.V., Buyan M.S., Samosudova I.B. Recurrence of cervical intraepithelial neoplasia: modern view on the problem.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (4): 34-38 (in Russian)
https://dx.doi.org/10.18565/aig.2024.4

CIN

HSIL

human papillomavirus

conization

recurrence

margin status

posttreatment surveillance

Full text (in Russian)

Loopik D.L., Bentley H.A., Eijgenraam M.N., IntHout J., Bekkers R.L.M., Bentley J.R. The natural history of cervical intraepithelial neoplasia grades 1, 2, and 3: a systematic review and meta-analysis. J. Low Genit. Tract. Dis. 2021; 25: 221-31. https://dx.doi.org/10.1097/LGT.0000000000000604.
Skorstengaard M., Lynge E., Suhr J., Napolitano G. Conservative management of women with cervical intraepithelial neoplasia grade 2 in Denmark: a cohort study. BJOG. 2020; 127(6): 729-736. https://dx.doi.org/10.1111/1471-0528.16081.
Tainio K., Athanasiou A., Tikkinen K.A.O., Aaltonen R., Cárdenas J., Hernándes, Glazer-Livson S. et al. Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: systematic review and meta-analysis. BMJ. 2018; 360: k499. https://dx.doi.org/10.1136/bmj.k499.
Lycke K.D., Kahlert J., Petersen L.K., Damgaard R.K., Cheung L.C., Gravitt P.E. et al. Untreated cervical intraepithelial neoplasia grade 2 and subsequent risk of cervical cancer: population based cohort study. BMJ. 2023; 383: e075925. https://dx.doi.org/10.1136/bmj-2023-075925.
Kalliala I., Athanasiou A., Veroniki A.A., Salanti G., Efthimiou O., Raftis N. et al. Incidence and mortality from cervical cancer and other malignancies after treatment of cervical intraepithelial neoplasia: a systematic review and meta-analysis of the literature. Ann. Oncol. 2020; 31(2): 213-27. https://dx.doi.org/10.1016/j.annonc.2019.11.004.
Прилепская В.Н., Байрамова Г.Р., Асатурова А.В., Андреев А.О., Перемыкина А.В., Пронина В.А. Современные представления о предикторах и методах профилактики рецидивов цервикальной интраэпителиальной неоплазии после петлевой электроэксцизии. Акушерство и гинекология. 2020; 12: 81-8. [Prilepskaya V.N., Bairamova G.R., Asaturova A.V., Andreyev A.O., Peremykina A.V., Pronina V.A. Current understanding of predictors and methods for preventing recurrent cervical intraepithelial neoplasia after loop electrosurgical excision procedure. Obstetrics and Gynecology. 2020; (12): 81-8. (in Russian)]. https://dx.doi.org/10.18565/aig.2020.12.81-88.
Прилепская В.Н., Юрова М.В. Современные направления в диагностике, лечении и профилактике ВПЧ-ассоциированных заболеваний шейки матки (в помощь клиницисту). Гинекология. 2023; 25(2): 245-50. [Prilepskaya V.N., Iurova M.V. Current approaches in the diagnosis, treatment and prevention of HPV-associated cervical diseases: practical recommendations. A review. Gynecology. 2023; 25(2): 245-50. (in Russian)]. https://dx.doi.org/10.26442/20795696.2023.2.202193.
Tanaka Y., Ueda Y., Kakuda M., Kubota .S, Matsuzaki .S, Iwamiya T. et al. Predictors for recurrent/persistent high-grade intraepithelial lesions and cervical stenosis after therapeutic conization: a retrospective analysis of 522 cases. Int. J. Clin. Oncol. 2017; 22(5): 921-6. https://dx.doi.org/10.1007/s10147-017-1124-z.
Bogani G., Lalli L., Sopracordevole F., Ciavattini A., Ghelardi A., Simoncini T. et al. Development of a nomogram predicting the risk of persistencerRecurrence of cervical dysplasia. Vaccines (Basel). 2022; 10(4): 579. https://dx.doi.org/10.3390/vaccines10040579.
Arbyn M., Redman C.W.E., Verdoodt F., Kyrgiou M., Tzafetas M., Ghaem-Maghami S. et al. Incomplete excision of cervical precancer as a predictor of treatment failure: a systematic review and meta-analysis. Lancet Oncol. 2017; 18(12): 1665-79. https://dx.doi.org/10.1016/S1470-2045(17)30700-3.
Belkić K., Andersson S., Alder S., Mints M., Megyessi D. Predictors of treatment failure for adenocarcinoma in situ of the uterine cervix: Up to 14 years of recorded follow-up. Oncol. Lett. 2022; 25; 24(4): 357. https://dx.doi.org/10.3892/ol.2022.13477.
Bittencourt D.D., Zanine R.M., Sebastião A.P.M., Ribas C.M. Risk factors for persistence or recurrence of high-grade cervical squamous intraepithelial lesions. Rev. Col. Bras. Cir. 2023; 50: e20233537. https://dx.doi.org/10.1590/0100-6991e-20233537-en.
Garutti P., Borghi C., Bedoni C., Bonaccorsi G., Greco P., Tognon M. et al. HPV-based strategy in follow-up of patients treated for high-grade cervical intra-epithelial neoplasia: 5-year results in a public health surveillance setting. Eur. J. Obstet. Gynecol. Reprod. Biol. 2017; 210: 236-41. https://dx.doi.org/10.1016/j.ejogrb.2016.12.018.
Chen M., Li C., Cui Q., Zhou C., Chen P., Yao S. The efficacy of human papillomavirus prophylactic vaccination after conization in preventing cervical intraepithelial neoplasia recurrence: A prospective observational study in China. Eur. J. Obstet. Gynecol. Reprod. Biol. 2023; 286: 10-5. https://dx.doi.org/10.1016/j.ejogrb.2023.04.014.
Ikeda M., Mikami M., Yasaka M., Enomoto T., Kobayashi Y., Nagase S. 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. https://dx.doi.org/10.3802/jgo.2021.32.e68.
Fan A., Wang C., Han C., Wang Y., Xue F., Zhang L. Factors affecting residual/recurrent cervical intraepithelial neoplasia after cervical conization with negative margins. J. Med. Virol. 2018; 90(9): 1541-8. https://dx.doi.org/10.1002/jmv.25208.
Andersson S., Megyessi D., Belkić K., Alder S., Östensson E., Mints M. 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(3): 684. https://dx.doi.org/10.3892/ol.2021.12945.
Alder S., Megyessi D., Sundström K., Östensson E., Mints M., Belkić K. et al. Incomplete excision of cervical intraepithelial neoplasia as a predictor of the risk of recurrent disease-a 16-year follow-up study. Am. J. Obste.t Gynecol. 2020; 222(2): 172.e1-172.e12. https://dx.doi.org/10.1016/j.ajog.2019.08.042.
Sundqvist A., Nicklasson J., Olausson P., Borgfeldt C. Post-conization surveillance in an organized cervical screening program with more than 23,000 years of follow-up. Infect. Agent. Cancer. 2023; 18(1): 81. https://dx.doi.org/10.1186/s13027-023-00545-4.
Cuschieri K., Ronco G., Lorincz A., Smith L., Ogilvie G., Mirabello L. et al. Eurogin 2017 Roadmap: Triage strategies for the management of HPV-positive women in cervical screening programs. Int. J. Cancer. 2018; 143(4): 735-45. https://dx.doi.org/10.1002/ijc.31261.
Министерство здравоохранения Российской Федерации. Клинические рекомендации «Цервикальная интраэпителиальная неоплазия, эрозия и эктропион шейки матки». 2020. [Ministry of Health of the Russian Federation. Clinical guidelines “Cervical intraepithelial neoplasia, erosion and ectropion of the cervix”. 2020. (in Russian)].
Клинышкова Т.В. Стратегии цервикального скрининга: современный взгляд. Российский вестник акушера-гинеколога. 2023; 23(4): 20-6. [Klinyshkova T.V. Cervical screening strategies: a modern perspective. Russian Bulletin of Obstetrician-Gynecologist. 2023; 23(4): 20-6. (in Russian)].
Simms K.T., Keane A., Nguyen D.T.N., Caruana M., Hall M..T, Lui G. et al. Benefits, harms and cost-effectiveness of cervical screening, triage and treatment strategies for women in the general population. Nat. Med. 2023; 29(12): 3050-8. https://dx.doi.org/10.1038/s41591-023-02600-4.
Bogani G., Di Donato V., Sopracordevole F., Ciavattini A., Ghelardi A., Lopez S. 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. https://dx.doi.org/10.1016/j.ygyno.2020.08.025.
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. https://dx.doi.org/10.1186/s12905-023-02360-w.
Rositch A.F., Soeters H.M., Offutt-Powell T.N., Wheeler B.S., Taylor S.M., Smith J.S. The incidence of human papillomavirus infection following treatment for cervical neoplasia: a systematic review. Gynecol. Oncol. 2014; 132(3): 767-79. https://dx.doi.org/10.1016/j.ygyno.2013.12.040.
Giannini A., Di Donato V., Sopracordevole F., Ciavattini A., Ghelardi A., Vizza E. et al. Vaccines (Basel) 2023; 11(3): 698. https://dx.doi.org/10.3390/vaccines11030698.
Peng H., Liu W., Jiang J., Du H. Extensive lesions and a positive cone margin are strong predictors of residual disease in subsequent hysterectomy following conization for squamous intraepithelial lesion grade 2 or 3 study design. BMC Womens Health. 2023; 23(1): 454. https://dx.doi.org/10.1186/s12905-023-02568-w.
Murakami I., Ohno A., Ikeda M., Yamashita H., Mikami M., Kobayashi Y. et al. Analysis of pathological and clinical characteristics of cervical conization according to age group in Japan. Heliyon. 2020; 6(10): e05193. https://dx.doi.org/10.1016/j.heliyon.2020.e05193.
Kechagias K.S., Kalliala I., Bowden S.J., Athanasiou A., Paraskevaidi .M, Paraskevaidis E. et al. Role of human papillomavirus (HPV) vaccination on HPV infection and recurrence of HPV related disease after local surgical treatment: systematic review and meta-analysis. BMJ. 2022; 378: e070135. https://dx.doi.org/10.1136/bmj-2022-070135.
Eriksen D.O., Jensen P.T., Schroll J.B., Hammer A. Human papillomavirus vaccination in women undergoing excisional treatment for cervical intraepithelial neoplasia and subsequent risk of recurrence: a systematic review and meta-analysis. Acta Obstet. Gynecol. Scand. 2022; 101(6): 597-607. https://dx.doi.org/10.1111/aogs.14359.
Petráš M., Dvořák V., Lomozová D., Máčalík R., Neradová S., Dlouhý P. et al. Timing of HPV vaccination as adjuvant treatment of CIN2+ recurrence in women undergoing surgical excision: a meta-analysis and meta-regression. Sex. Transm. Infect. 2023; 99(8): 561-70. https://dx.doi.org/10.1136/sextrans-2023-055793.

Received 15.01.2024

Accepted 02.04.2024

Tatiana V. Klinyshkova, Dr. Med. Sci., Professor, Professor of the Obstetrics and Gynecology Department, Omsk State Medical University, Ministry of Health of Russia, 644099, Russia, Omsk, Lenina str., 12, klin_tatyana@mail.ru, https://orcid.org/0000-0002-0544-8184
Maria S. Buyan, PhD, obstetrician-gynecologist, Gynecological hospital, 644052, Russia, Omsk, 22nd Рarty congress str., 4, mam_agata@mail.ru,
https://orcid.org/0000-0002-8413-3809
Irina B. Samosudova, PhD, obstetrician-gynecologist, Clinical Diagnostic Center "Ultramed", Russia, Omsk, Chkalova str., 12, i.samosudova@mail.ru,
https://orcid.org/0000-0002-2853-0471
Corresponding author: Tatiana V. Klinyshkova, klin_tatyana@mail.ru

Recurrence of cervical intraepithelial neoplasia: modern view on the problem

Klinyshkova T.V., Buyan M.S., Samosudova I.B.

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