After treatment for cervical adenocarcinoma in situ, patients remain a risk for recurrent adenocarcinoma in situ, cervical intraepithelial grade 3, or cervical cancer.

This study aimed to determine the optimal follow-up strategy for high-risk human papillomavirus and cytology testing in conservatively treated patients with adenocarcinoma in situ.

Patients were selected from a nationwide, retrospective cohort that included pathology reports from the Dutch Nationwide Pathology Databank (Palga) and survival data from the Central Bureau for Genealogy for patients conservatively treated for adenocarcinoma in situ between 1990 and 2021. The main outcome was the 5-year cumulative incidence of recurrent adenocarcinoma in situ, cervical intraepithelial neoplasia grade 3, or cervical cancer stratified by single and consecutive human papillomavirus test and/or cytology results at 6, 12, 18, and 24 months.

A total of 3411 patients were eligible for analysis. High-risk human papillomavirus test and/or cytology results in the first 5 years of follow-up were available in 3312 of 3411 patients (97.1%), including 5207 high-risk human papillomavirus test results of 1928 patients and 13,369 cytology results of 3306 patients. Up to 5 years after a single high-risk human papillomavirus test at 6 months after treatment, the incidence of recurrent adenocarcinoma in situ, cervical intraepithelial neoplasia grade 3, or cervical cancer was lower among high-risk human papillomavirus–negative patients (2.3%; 95% confidence interval, 0.8–3.7) compared with high-risk human papillomavirus–positive patients (20.1%; 95% confidence interval, 14.2–25.5). Patients with normal cytology results 6 months after treatment for adenocarcinoma in situ had a lower incidence of recurrent adenocarcinoma in situ, cervical intraepithelial neoplasia grade 3, or cervical cancer (3%; 95% confidence interval, 2.2–3.8) compared with patients with low-grade (5.9%; 95% confidence interval, 3.4–8.4) or high-grade cytology (52.1%; 95% confidence interval, 42.7–59.9). The 5-year cumulative incidence of recurrent adenocarcinoma in situ, cervical intraepithelial neoplasia grade 3, or cervical cancer among patients testing negative for high-risk human papillomavirus consecutively at 6 and 12, 6 and 18, and 6 and 24 months was 0.6% (95% confidence interval, 0–1.8), 1.1% (95% confidence interval, 0–3.4), and 0% (95% confidence interval not applicable), respectively. Similarly, for patients with consecutive normal cotest results (high-risk human papillomavirus–negative with normal or low-grade cytology) at 6 and 12, 6 and 18, and 6 and 24 months, the 5-year cumulative incidence of recurrent adenocarcinoma in situ, cervical intraepithelial neoplasia grade 3, or cervical cancer was 0.6% (95% confidence interval, 0–1.8), 1.2% (95% confidence interval, 0–3.5), and 0% (95% confidence interval not applicable), respectively.

After 2 consecutive negative high-risk human papillomavirus or normal cotests within 2 years after conservative adenocarcinoma in situ treatment, the risk of recurrent adenocarcinoma in situ, cervical intraepithelial neoplasia grade 3, or cervical cancer is low, and it seems acceptable to refer patients back to the national cervical cancer screening program, if applicable.