Evaluating efficacy of active surveillance for CIN2

Cervical intraepithelial neoplasia (CIN) can be detected by cervical cancer screening, preventing progression to cervical cancer. Categories of CIN based on severity include CIN1, CIN2, and CIN3, which are mild, moderate, and severe, respectively. 

Women with CIN2 or higher are at an increased risk of cervical cancer and are often recommended immediate loop electrosurgical excision procedure (LEEP). However, LEEP has been associated with significant rates of CIN2 regression, indicating immediate LEEP of CIN2 may lead to overtreatment.

Multiple countries have been engaging in active surveillance over LEEP for patients with CIN2. However, there is little data on the outcomes of active surveillance for CIN2. To evaluate regression and progression rates in women undergoing active surveillance for CIN2 in Denmark, investigators conducted a nationwide population-based cohort study.

Participants included women aged 18 to 40 years diagnosed with CIN2 for the first time between January 1, 1998, and December 31, 2020, receiving active surveillance. Exclusion criteria included a previous record of CIN2+, LEEP, vulvar, or vaginal cancer.

Investigators defined active surveillance as, “having a subsequent record of a cervical biopsy within 10 months after their CIN2 diagnosis.” Records in the Danish Pathology Registry were evaluated to determine whether women were receiving active surveillance.

Free and equal cervical cancer screening has been offered to women aged 23 to 59 years in Denmark since the 1960s, with women aged 60 to 64 years included since 2007. Active surveillance is available for women planning future pregnancy, making it often offered to women aged below 40 years.

Women receiving active surveillance complete semiannual follow-up visits for up to 2 years. Patients with a regression to CIN1 or normal receive an additional cervical cytology after 1 year, while those with progression to CIN3 or persistent disease after 2 years are recommended LEEP.

Data was obtained from the Danish National Pathology Registry, Civil Registration System, Danish Cancer Registry, and Danish Patient Registry. Diagnoses on subsequent cervical histologic samples were used to determine regression and progression rates.

There were 11,056 women included in the final analysis, of whom 71% were aged under 30 years, 82% had an abnormal index cytology, and 53% were diagnosed after 2013. A histologic regression within 6 months was reported in 27.9% of women, and in 62.9% at 24 months of follow-up. 

Of women who regressed, 90% reported regression within the first 12 months, 54% reported regressing to normal, and 46% reported regressing to CIN1.

Histologically verified progression was reported in 15.1% of patients within 6 months and 33.3% within 24 months. Of patients who progressed, 90% reported progression within the first 12 months. Cervical cancer within 24 months was reported by 0.3% of participants, none of which were worse than stage 2 and almost 60% of which were stage 1a.

LEEP within 24 months was reported in 37.6% of women, 75% of whom underwent the procedure within 1 year. The risk of LEEP was reduced by 11% in women aged 19 to 22 years at CIN2 diagnosis compared to women aged 23 to 29 years.

These results indicated efficacy from active surveillance in measuring regression and progression in women with CIN2. Investigators recommended research be conducted to determine long-term outcomes of active surveillance.

Reference

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;229:656.e1-15.