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Original Research

Open Access

Predictive value of HPV genotyping for recurrence of CIN2−3 in women treated by LEEP with negative resection margins

  • In Yeong Jo1
  • Woo Dae Kang1,*,
  • U Chul Ju1
  • Seok Mo Kim1

1Department of Obstetrics and Gynecology, Chonnam National University Medical School, 61469 Gwangju, Republic of Korea

DOI: 10.22514/ejgo.2023.047 Vol.44,Issue 5,October 2023 pp.97-103

Submitted: 03 April 2023 Accepted: 28 April 2023

Published: 15 October 2023

*Corresponding Author(s): Woo Dae Kang E-mail:


The aim of our study was to determine whether the HPV genotype identified by the HPV DNA chip (HDC) test could predict the recurrence of high-grade cervical intraepithelial neoplasia (CIN2–3) in women who had undergone a loop electrosurgical excision procedure (LEEP) and had negative margins. We analyzed the data of 1021 women with CIN2–3 treated by LEEP where histology confirmed negative resection margins. The women were followed up with HDC and endocervical cytology tests at 3, 6, 9, 12, 18 and 24 months during the first 2 years and annually thereafter. Among the 1021 patients, the pre-LEEP HDC test was positive for 992 (97.2%). A total of 90 (8.8%) patients experienced recurrence of CIN2–3 and the post-LEEP follow-up HDC tests were positive, thus demonstrating a persistent high-risk HPV infection of the same genotype, which showed a sensitivity and negative predictive value of 100%in predicting recurrence. We also examined the correlation between pre-LEEP high-risk HPV genotypes and recurrence. The most common subtypes were HPV16, HPV18 and HPV31. Persistence of HPV18 had the highest risk of recurrence of CIN2–3 (p < 0.05). Our study suggests that type-specific persistent high-risk HPV infection, particularly the HPV18 subtype, is a significant predictor of recurrence in patients with negative resection margins in the LEEP specimens. Thus, these patients require careful monitoring, and gynecologic oncologists should conduct short-term follow-up tests.


Loop electrosurgical excision procedure; High-grade cervical intraepithelial neoplasia; Cone margin; High-risk-human papillomavirus testing

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In Yeong Jo,Woo Dae Kang,U Chul Ju,Seok Mo Kim. Predictive value of HPV genotyping for recurrence of CIN2−3 in women treated by LEEP with negative resection margins. European Journal of Gynaecological Oncology. 2023. 44(5);97-103.


[1] Luthra UK, Prabhakar AK, Seth P, Agarwal SS, Murthy NS, Bhatnagar P, et al. Natural history of precancerous and early cancerous lesions of the uterine cervix. Acta Cytologica. 1987; 31: 226–234.

[2] Cohen PA, Jhingran A, Oaknin A, Denny L. Cervical cancer. The Lancet. 2019; 393: 169–182.

[3] Arbyn M, Tommasino M, Depuydt C, Dillner J. Are 20 human papillomavirus types causing cervical cancer? The Journal of Pathology. 2014; 234: 431–435.

[4] Chen L, Liu L, Tao X, Guo L, Zhang H, Sui L. Risk factor analysis of persistent high-grade squamous intraepithelial lesion after LEEP electrosurgical procedure conization. Journal of Lower Genital Tract Disease. 2019; 23: 24–27.

[5] Alonso I, Torné A, Puig-Tintoré LM, Esteve R, Quinto L, Campo E, et al. Pre- and post-conization high-risk HPV testing predicts residual/recurrent disease in patients treated for CIN 2–3. Gynecologic Oncology. 2006; 103: 631–636.

[6] Massad LS, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M, et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstetrics & Gynecology. 2013; 121: 829–846.

[7] 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. American Journal of Obstetrics and Gynecology. 2020; 222: 172.e1–172.e12.

[8] Choi Y, Jung W, Nam J, Choi H, Park C. Detection of HPV genotypes in cervical lesions by the HPV DNA chip and sequencing. Gynecologic Oncology. 2005; 98: 369–375.

[9] Kyrgiou M, Athanasiou A, Paraskevaidi M, Mitra A, Kalliala I, Martin-Hirsch P, et al. Adverse obstetric outcomes after local treatment for cervical preinvasive and early invasive disease according to cone depth: systematic review and meta-analysis. The BMJ. 2016; 354: i3633.

[10] Sadler L, Saftlas A, Wang W, Exeter M, Whittaker J, McCowan L. Treatment for cervical intraepithelial neoplasia and risk of preterm delivery. Obstetrical & Gynecological Survey. 2004; 59: 698–699.

[11] Massad LS, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M, et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstetrics & Gynecology. 2013; 121: 829–846.

[12] Ding T, Li L, Duan R, Chen Y, Yang B, Xi M. Risk factors analysis of recurrent disease after treatment with a loop electrosurgical excision procedure for high‐grade cervical intraepithelial neoplasia. International Journal of Gynecology & Obstetrics. 2023; 160: 538–547.

[13] Arbyn M, Redman CWE, 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. The Lancet Oncology. 2017; 18: 1665–1679.

[14] Yang EJ, Kim NR, Choi JY, Kim WY, Lee SJ. Loop electrosurgical excision procedure combined with cold coagulation for cervical intraepithelial neoplasia and adenocarcinoma in-situ: a feasible treatment with a low risk of residual/recurrent disease. Infectious Agents and Cancer. 2020; 15: 58.

[15] PRATO B, GHELARDI A, GADDUCCI A, MARCHETTI I, Di CRISTOFANO C, Di COSCIO G, et al. Correlation of recurrence rates and times with posttreatment human papillomavirus status in patients treated with loop electrosurgical excision procedure conization for cervical squamous intraepithelial lesions. International Journal of Gynecological Cancer. 2008; 18: 90–94.

[16] Bollen LJM, Tjong-A-Hung SP, van der Velden J, Mol B, ten Kate FWJ, ter Schegget J, et al. Prediction of recurrent and residual cervical dysplasia by human papillomavirus detection among patients with abnormal cytology. Gynecologic Oncology. 1999; 72: 199–201.

[17] Fernández‐Montolí M, Tous S, Medina G, Castellarnau M, Gar-cía‐Tejedor A, Sanjosé S. Long‐term predictors of residual or recurrent cervical intraepithelial neoplasia 2–3 after treatment with a large loop excision of the transformation zone: a retrospective study. BJOG: An International Journal of Obstetrics & Gynaecology. 2020; 127: 377–387.

[18] Gogoladze T, Tkeshelashvili V, Alibegashvili T, Jorbenadze M, Manjgal-adze K. Evaluation of residual lesions following conservative treatment of high grade cervical intraepithelial neoplasia. Georgian Medical News. 2018; 284: 13–18.

[19] Zhang J, Cheng K, Wang Z. Prevalence and distribution of human papillomavirus genotypes in cervical intraepithelial neoplasia in China: a meta-analysis. Archives of Gynecology and Obstetrics. 2020; 302: 1329–1337.

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