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Incomplete excision of cervical intraepithelial neoplasia as a predictor of the risk of recurrent disease: a 16-year follow-up study
Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institute, Stockholm, Sweden.
Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institute, Stockholm, Sweden.
Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden; Karolinska University Laboratory, Karolinska University Hospital, Stockholm, Sweden.
Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institute, Stockholm, Sweden.
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2020 (English)In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 222, no 2, p. 172.e1-172.e12Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Women treated for high-grade cervical intraepithelial neoplasia (CIN, grade 2 or 3) are at elevated risk of developing cervical cancer. Suggested factors identifying women at highest risk for recurrence post-therapeutically include incomplete lesion excision, lesion location, size and severity, older age, treatment modality and presence of high-risk human papilloma virus (hrHPV) after treatment. This question has been intensively investigated over decades, but there is still substantial debate as to which of these factors or combination of factors most accurately predict treatment failure.

OBJECTIVES: In this study, we examine the long-term risk of residual/recurrent CIN2+ among women previously treated for CIN2 or 3 and how this varies according to margin status (considering also location), as well as comorbidity (conditions assumed to interact with hrHPV acquisition and/or CIN progression), post-treatment presence of hrHPV and other factors.

STUDY DESIGN: This prospective study included 991 women with histopathologically-confirmed CIN2/3 who underwent conization in 2000-2007. Information on the primary histopathologic finding, treatment modality, comorbidity, age and hrHPV status during follow-up and residual/recurrent CIN2+ was obtained from the Swedish National Cervical Screening Registry and medical records. Cumulative incidence of residual/recurrent CIN2+ was plotted on Kaplan-Meier curves, with determinants assessed by Cox regression.

RESULTS: During a median of 10 years and maximum of 16 years follow-up, 111 patients were diagnosed with residual/recurrent CIN2+. Women with positive/uncertain margins had a higher risk of residual/recurrent CIN2+ than women with negative margins, adjusting for potential confounders (hazard ratio (HR)=2.67; 95% confidence interval (CI): 1.81-3.93). The risk of residual/recurrent CIN2+ varied by anatomical localization of the margins (endocervical: HR=2.72; 95%CI: 1.67-4.41) and both endo- and ectocervical (HR=4.98; 95%CI: 2.85-8.71). The risk did not increase significantly when only ectocervical margins were positive/uncertain. The presence of comorbidity (autoimmune disease, human immunodeficiency viral infection, hepatitis B and/or C, malignancy, diabetes, genetic disorder and/or organ transplant) was also a significant independent predictor of residual/recurrent CIN2+. In women with positive hrHPV findings during follow-up, the HR of positive/uncertain margins for recurrent/residual CIN2+ increased significantly compared to women with hrHPV positive findings but negative margins.

CONCLUSIONS: Patients with incompletely excised CIN2/3 are at increased risk of residual/recurrent CIN2+. Margin status combined with hrHPV results and consideration of comorbidity may increase the accuracy for predicting treatment failure.

Place, publisher, year, edition, pages
Elsevier, 2020. Vol. 222, no 2, p. 172.e1-172.e12
Keywords [en]
Cox regression analysis, conization, ectocervical margins, endocervical margins, excisional diathermy, invasive cervical cancer, laser, margin status, pre-cancerous cervical lesions, treatment failure
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
URN: urn:nbn:se:oru:diva-76100DOI: 10.1016/j.ajog.2019.08.042ISI: 000509495500016PubMedID: 31473226Scopus ID: 2-s2.0-85073935509OAI: oai:DiVA.org:oru-76100DiVA, id: diva2:1349800
Funder
Swedish Cancer Society, 11 0544 CAN 2011/471Stockholm County Council, 20130097 20160155 20160083King Gustaf V Jubilee Fund, 154022 151202
Note

Funding Agencies:

European Federation for Colposcopy (Birmingham, UK)  

COSPCC study (University Hospital of Amiens, Amiens, France) - Institut National du Cancer (Paris, France)  

COHEAHR Network - 7th Framework Programme of DG Research and Innovation, European Commission (Brussels, Belgium)  603019

Available from: 2019-09-10 Created: 2019-09-10 Last updated: 2020-02-06Bibliographically approved

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