Optimal follow-up strategy using high-risk human papillomavirus testing and cytology after conservative treatment for cervical adenocarcinoma in situ

Mirte Schaafsma; Teska N Schuurman; Ingrid S van Maurik; Ruud L M Bekkers; Petra L M Zusterzeel; Maaike C G Bleeker; Albert G Siebers; Constantijne H Mom; Johannes Berkhof; Nienke E van Trommel

doi:10.1016/j.ajog.2025.05.040

Optimal follow-up strategy using high-risk human papillomavirus testing and cytology after conservative treatment for cervical adenocarcinoma in situ

Am J Obstet Gynecol. 2025 Jun 5:S0002-9378(25)00367-9. doi: 10.1016/j.ajog.2025.05.040. Online ahead of print.

Affiliations

¹ Department of Gynecologic Oncology, Center of Gynecologic Oncology Amsterdam, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Department of Pathology, Amsterdam University Medical Center location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; Imaging and Biomarkers, Cancer Center Amsterdam, Amsterdam, The Netherlands. Electronic address: m.schaafsma@amsterdamumc.nl.
² Department of Gynecologic Oncology, Center of Gynecologic Oncology Amsterdam, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
³ Department of Epidemiology, Noordwest Ziekenhuisgroep, Alkmaar, The Netherlands.
⁴ Department of Gynecology, Catharina Hospital, Eindhoven, The Netherlands; Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Obstetrics and Gynaecology, Maastricht University Medical Center+ and GROW - Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands.
⁵ Department of Obstetrics and Gynaecology, Maastricht University Medical Center+ and GROW - Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands.
⁶ Department of Pathology, Amsterdam University Medical Center location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; Imaging and Biomarkers, Cancer Center Amsterdam, Amsterdam, The Netherlands.
⁷ Palga, the Dutch Nationwide Pathology Databank, Houten, The Netherlands.
⁸ Imaging and Biomarkers, Cancer Center Amsterdam, Amsterdam, The Netherlands; Department of Gynecologic Oncology, Center of Gynecologic Oncology Amsterdam, Amsterdam University Medical Center location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
⁹ Department of Epidemiology and Data Science, Amsterdam University Medical Center, location Vrije Universiteit Amsterdam, The Netherlands.

PMID: 40482946
DOI: 10.1016/j.ajog.2025.05.040

Abstract

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

Objective: 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.

Study design: 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.

Results: 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.

Conclusion: 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.

Keywords: adenocarcinoma in situ; cervical cancer; cytology; follow-up; high-risk human papillomavirus.