Background
Women treated for high-grade cervical intraepithelial neoplasia (grade 2 or 3) are
at elevated risk for 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 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.
Objective
In this study, we examine the long-term risk of residual/recurrent high-grade cervical
intraepithelial neoplasia among women previously treated for cervical intraepithelial
neoplasia 2/3 and how this varies according to margin status (considering also location),
as well as comorbidity (conditions assumed to interact with high-risk human papilloma
virus acquisition and/or cervical intraepithelial neoplasia progression), posttreatment
presence of high-risk human papilloma virus, and other factors.
Materials and Methods
This prospective study included 991 women with histopathologically confirmed cervical
intraepithelial neoplasia 2/3 who underwent conization in 2000–2007. Information on
the primary histopathologic finding, treatment modality, comorbidity, age, and high-risk
human papilloma virus status during follow-up, and residual/recurrent high-grade cervical
intraepithelial neoplasia was obtained from the Swedish National Cervical Screening
Registry and medical records. Cumulative incidence of residual/recurrent high-grade
cervical intraepithelial neoplasia was plotted on Kaplan–Meier curves, with determinants
assessed by Cox regression.
Results
During a median of 10 years and maximum of 16 years of follow-up, 111 patients were
diagnosed with residual/recurrent high-grade cervical intraepithelial neoplasia or
worse. Women with positive/uncertain margins had a higher risk of residual/recurrent
high-grade cervical intraepithelial neoplasia or worse than women with negative margins,
adjusting for potential confounders (hazard ratio, 2.67; 95% confidence interval,
1.81–3.93). The risk of residual/recurrent high-grade cervical intraepithelial neoplasia
or worse varied by anatomical localization of the margins (endocervical: hazard ratio,
2.72; 95% confidence interval, 1.67–4.41) and both endo- and ectocervical (hazard
ratio, 4.98; 95% confidence interval, 2.85–8.71). The risk did not increase significantly
when only ectocervical margins were positive or 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 high-grade cervical intraepithelial neoplasia
or worse. In women with positive high-risk human papilloma virus findings during follow-up,
the hazard ratio of positive/uncertain margins for recurrent/residual high-grade cervical
intraepithelial neoplasia or worse increased significantly compared to that in women
with positive high-risk human papilloma virus findings but negative margins.
Conclusion
Patients with incompletely excised cervical intraepithelial neoplasia 2/3 are at increased
risk for residual/recurrent high-grade cervical intraepithelial neoplasia or worse.
Margin status combined with high-risk human papilloma virus results and consideration
of comorbidity may increase the accuracy for predicting treatment failure.
Key words
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Article info
Publication history
Published online: August 29, 2019
Accepted:
August 24,
2019
Received in revised form:
August 7,
2019
Received:
May 21,
2019
Footnotes
M.A. discloses support from the 7th Framework Programme of DG Research and Innovation, European Commission, Grant, Meta-analysis on new methods to prevent HPV-related cancer via the COHEAHR Network (grant No. 603019). The other authors report no conflict of interest.
Support for this work was provided by the Swedish Cancer Foundation (11 0544, CAN 2011/471) URL: www.cancerfonden.se; Stockholm County Council (20130097, 20160155) URL: www.skl.se; The Gustaf V Jubilee Fund (154022) URL: www.rahfo.se, The Gustaf V Jubilee Fund (151202) URL: www.rahfo.se; Stockholm County Council (20160083) URL: www.skl.se, European Federation for Colposcopy (Birmingham, UK); the COSPCC study (University Hospital of Amiens, Amiens, France), funded by Institut National du Cancer (Paris, France); and the COHEAHR Network (grant number 603019), funded by the 7th Framework Programme of DG Research and Innovation, European Commission (Brussels, Belgium). The study sponsors had no role in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.
Cite this article as: Alder S, Megyessi D, Sundström 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 Obstet Gynecol 2020;222:172.e1-12.
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