Predictors of residual disease after loop electrosurgical excision procedure

Ana Carolina Dantas Fabricio de Hollanda; Ana Katherine Gonçalves; Carlos André Jatobá; Teresa Neumann Dantas Fabricio; Adalberto Fabricio da Silva; Ricardo Ney Cobucci

Ana Carolina Dantas Fabricio de Hollanda Gynecological Resident, Federal University of Rio Grande do Norte, UFRN, Natal, Brazil
Ana Katherine Gonçalves Department of Gynecology and Obstetrics, Federal University of Rio Grande do Norte, UFRN, Natal, Brazil
Carlos André Jatobá Department of Pathology, Federal University of Rio Grande do Norte, UFRN, Natal, Brazil
Teresa Neumann Dantas Fabricio Teaching and Research Management, Federal University of Rio Grande do Norte, UFRN, Natal, Brazil
Adalberto Fabricio da Silva Federal University of Rio Grande do Norte, UFRN, Natal, Brazil
Ricardo Ney Cobucci Department of Gynecology and Obstetrics, Potiguar University, UnP, Natal, Brazil

Keywords: Cervical intraepithelial neoplasia, Minimal residual disease, Conization, Papillomavirus infections

Abstract

The study aims to evaluate the importance of resection margins in the risk of residual disease (RD) and to investigate other factors that could potentially predict RD before patients engage in follow-up. Eighty-six women with a histologically confirmed diagnosis of cervical intraepithelial neoplasms (CIN) treated by loop electrosurgical excision procedure (LEEP), were included in this retrospective study, between January 2015 and May 2016. Age, smoking habit, menopause status, and LEEP margins were evaluated as possible predictors of RD. The mean age at diagnosis was 35.8 years (range 18-61). The mean follow-up period was 12 months. 11.6% of patients (09/86) were lost in follow-up. 64% of patients (55/86) had clear margins in the specimen and 34.8% of patients had positive surgical margins (30/86). In 1.2% of patients (01/86) the resection margins were uncertain. RD was demonstrated by positive Pap Smear and by colposcopy-guided biopsy in 26.7% of patients (23/86). We found significant differences in the frequency of RD depending on the status of margins: 65.2% of cases with positive margins vs. 24.5% of cases with negative margins (p<0.0001). Multivariate analysis showed that only high-grade squamous intraepithelial lesion (H-SIL) detection in cervical biopsy and status of the LEEP margins were significantly predictive of RD (OR 5.4, 95%CI 1.08-27.7, p<0.05 and OR 7.05, 95%CI 2.1-23.1, p=0.001; respectively). The combination of histological examination of resection margins plus H-SIL detection in cervical biopsy would help to classify LEEP-treated patients into categories of different risk levels of residual disease.

DOI: http://dx.doi.org/10.5281/zenodo.1173700

References

1. Chen Y, Lu H, Wan X, Lv W, Xie X. Factors associated with positive margins in patients with cervical intraepithelial neoplasia grade 3 and postconization management. Int J Gynecol Obstet. 2009; 107(2): 107-110.

2. Bittencourt DD, Zanine RM, Sebastião AM, Taha NS, Speck NG, Ribalta JCL. Number of fragments, margin status and thermal artifacts of conized specimens from LLETZ surgery to treat cervical intraepithelial neoplasia. Sao Paulo Med J. 2012; 130(2): 92-96.

3. Prendiville W, Cullimore J, Norman S. Large loop excision of the transformation zone (LLETZ): a new method of management for women with cervical intraepithelial neoplasia. Br J Obstet Gynecol. 1989; 96: 1054-1060.

4. van Hamont D, van Ham MAPC, van der Zanden PHTH, Keijser KGG, Bulten J, Melchers WJG, et al. Long-term follow-up after large-loop excision of the transformation zone: evaluation of 22 years treatment of high-grade cervical intraepithelial neoplasia. Int J Gynecol Cancer. 2006; 16(2): 615-619.

5. Papoutsis D, Rodolakis A, Mesogitis S, Sotiropoulou M, Antsaklis A. Appropriate cone dimensions to achieve negative excision margins after large loop excision of transformation zone in the uterine cervix for cervical intraepithelial neoplasia. Gynecol Obstet Invest. 2013; 75(3): 163-168.

6. Serati M, Siesto G, Carollo S, Formenti G, Riva C, Cromi A, et al. Risk factors for cervical intraepithelial neoplasia recurrence after conization: a 10-year study. Eur J Obstet Gynecol Reprod Biol. 2012; 165(1): 86-90.

7. Ghaem-Maghami S, Sagi S, Majeed G, Soutter WP. Incomplete excision of cervical intraepithelial neoplasia and risk of treatment failure: a meta-analysis. Lancet Oncol. 2007; 8(11): 985-993.

8. Treacy A, Devaney D, Mulligan NJ, Boyd W, Keane JC. Can a more detailed evaluation of excision margins refine cytologic follow-up of women post-LLETZ for high-grade dysplasia? Int J Gynecol Pathol. 2010; 29(5): 479-482.

9. Lubrano A, Medina N, Benito V, Arencibia O, Falcón JM, Leon L, et al. Follow-up after LLETZ: a study of 682 cases of CIN 2–CIN 3 in a single institution. Eur J Obstet Gynecol Reprod Biol. 2012; 161(1): 71-74.

10. Baloglu A, Uysal D, Bezircioglu I, Bicer M, Inci A. Residual and recurrent disease rates following LEEP treatment in high-grade cervical intraepithelial lesions. Arch Gynecol Obstet. 2010; 282(1): 69-73.

11. Fu Y, Cheng X, Wang X, Xie X, Lü W, Chen C, et al. Residual disease and risk factors in patients with high-grade cervical intraepithelial neoplasia and positive margins after initial conization. Ther Clin Risk Manag. 2015; 2015(11): 851.

12. Figueira P, Reis B, Tacla M. Positive margins at loop electrosurgical excision procedure: are they a predictor of residual cervical intraepithelial neoplasia? Rev Bras Genitoscopia. 2008; 3(2): 41-45.

13. Nayar R, Wilbur DC. The Pap test and Bethesda 2014. Acta Cytologica. 2015; 59: 121-132.

14. Kalliala I, Anttila A, Pukkala E, Nieminen P. Risk of cervical and other cancers after treatment of cervical intraepithelial neoplasia: retrospective cohort study. BMJ. 2005; 331: 1183-1185.

15. Cejtin HE, Zimmerman L, Mathews M, Patel A. Predictors of persistent or recurrent disease after loop electrosurgical excision procedure. J Low Genit Tract Dis. 2017; 21(1): 59-63.

16. Liss J, Alston M, Krull MB, Mazzoni SE. Predictors of positive margins at time of loop electrosurgical excision procedure. J Low Genit Tract Dis. 2017; 21(1): 64-66.

17. Nunes JD, Vidal FC, Ferraro CT, Chein MB, Brito LM, Monteiro SC. Molecular detection of human papillomavirus in Brazilian women with cervical intrapithelial neoplasia in a northeast Brazilian city. Genet Mol Res. 2014; 13(4): 9077-9085.