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. 2023 Nov 29:383:e075925.
doi: 10.1136/bmj-2023-075925.

Untreated cervical intraepithelial neoplasia grade 2 and subsequent risk of cervical cancer: population based cohort study

Kathrine Dyhr Lycke  1   2 , Johnny Kahlert  3 , Lone Kjeld Petersen  4   5 , Rikke Kamp Damgaard  6   2 , Li C Cheung  7 , Patti E Gravitt  8 , Anne Hammer  6   2
Affiliations

Untreated cervical intraepithelial neoplasia grade 2 and subsequent risk of cervical cancer: population based cohort study

Kathrine Dyhr Lycke et al. BMJ. .

Abstract

Objective: To describe the long term risk of cervical cancer in women with untreated (that is, undergoing active surveillance) or immediately treated cervical intraepithelial neoplasia grade 2 (CIN2).

Design: Nationwide population based historical cohort study.

Setting: Danish healthcare registries.

Participants: Women with CIN2 diagnosed in 1998-2020 and aged 18-40 years at diagnosis, who had either active surveillance or immediate treatment with large loop excision of the transformation zone (LLETZ). Women with a previous record of CIN2 or worse or LLETZ were excluded.

Main outcome measure: A Weibull survival model for interval censored time-to-event data was used to estimate the cumulative risk of cervical cancer. Inverse probability treatment weighting was used to adjust estimates for age, index cytology, calendar year, and region of residence.

Results: The cohort included 27 524 women with CIN2, of whom 12 483 (45%) had active surveillance and 15 041 (55%) had immediate LLETZ. During follow-up, 104 cases of cervical cancer were identified-56 (54%) in the active surveillance group and 48 (46%) in the LLETZ group. The cumulative risk of cervical cancer was comparable across the two groups during the active surveillance period of two years. Thereafter, the risk increased in the active surveillance group, reaching 2.65% (95% confidence interval 2.07% to 3.23%) after 20 years, whereas it remained stable in the LLETZ group at 0.76% (0.58% to 0.95%).

Conclusions: Undergoing active surveillance for CIN2, thereby leaving the lesion untreated, was associated with increased long term risk of cervical cancer compared with immediate LLETZ. These findings show the importance of continued follow-up of women having active surveillance.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the Danish Cancer Society, Central Region Denmark, Carpenter Axel Kastrup-Nielsen’s Memorial Fund, Manufacturer Einar Willumsen’s Memorial Fund, and Merchant AV Lykfeldt’s Grant; KDL has received a speaker’s fee from AstraZeneca; RKD and AH have received reagents at reduced cost from Roche Denmark; LP has received a speaker’s fee from MSD; no other relationships or activities that could appear to have influenced the submitted work.

Figures

Fig 1
Fig 1
Flowchart of study population. CIN2=cervical intraepithelial neoplasia grade 2; LLETZ=large loop excision of transformation zone
Fig 2
Fig 2
Cumulative risk of cervical cancer among women with cervical intraepithelial neoplasia grade 2 (CIN2) having active surveillance or immediate large loop excision of transformation zone (LLETZ). Model 1=follow-up from date of CIN2 diagnosis; model 2=follow-up from date of CIN2 diagnosis, with women in active surveillance group who were treated with LLETZ within 28 months of follow-up censored at date of LLETZ. An interactive version of this graphic is available at https://public.flourish.studio/visualisation/15560724/
Fig 3
Fig 3
Cumulative risk of cervical cancer among women with cervical intraepithelial neoplasia grade 2 (CIN2) having active surveillance or immediate large loop excision of transformation zone (LLETZ), stratified by age (<30, ≤30). Graph is based on model 1. An interactive version of this graphic is available at https://public.flourish.studio/visualisation/15561284/
See this image and copyright information in PMC

References

    1. Tainio K, Athanasiou A, Tikkinen KAO, et al. Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: systematic review and meta-analysis. BMJ 2018;360:k499. 10.1136/bmj.k499 - DOI - PMC - PubMed
    1. Loopik DL, Bentley HA, Eijgenraam MN, IntHout J, Bekkers RLM, Bentley JR. 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. 10.1097/LGT.0000000000000604 - DOI - PubMed
    1. Lycke KD, Kahlert J, Damgaard RK, et al. Clinical course of cervical intraepithelial neoplasia grade 2: a population-based cohort study. Am J Obstet Gynecol 2023;S0002-9378(23)00542-2. 10.1016/j.ajog.2023.08.008 - DOI - PubMed
    1. Kyrgiou M, Athanasiou A, Paraskevaidi M, et al. Adverse obstetric outcomes after local treatment for cervical preinvasive and early invasive disease according to cone depth: systematic review and meta-analysis. BMJ 2016;354:i3633. 10.1136/bmj.i3633 - DOI - PMC - PubMed
    1. Athanasiou A, Veroniki AA, Efthimiou O, et al. Comparative effectiveness and risk of preterm birth of local treatments for cervical intraepithelial neoplasia and stage IA1 cervical cancer: a systematic review and network meta-analysis. Lancet Oncol 2022;23:1097-108. 10.1016/S1470-2045(22)00334-5 - DOI - PMC - PubMed