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

Objective: After treatment for cervical adenocarcinoma in situ (AIS) patients remain at risk for recurrent AIS, high-grade cervical intraepithelial neoplasia, and cervical carcinoma (combined AIS/CIN3+). This study aimed to determine the optimal follow-up strategy for high-risk HPV and cytology testing in conservatively treated patients with AIS.

Study design: Patients were selected from a nationwide, retrospective cohort, in which pathology reports from the Dutch Nationwide Pathology databank (Palga) and survival data from the Central Bureau of Genealogy were collected of patients conservatively treated for AIS between 1990 and 2021. The main outcomes were the 5-year cumulative incidence of AIS/CIN3+ stratified by single and consecutive HPV test and/or cytology results at 6, 12, 18 and 24 months.

Results: 3,411 patients were eligible for analysis. High-risk HPV and/or cytology results in the first 5 years of follow-up were available in 3,312 of 3,411 patients (97.1%), including 5,207 high-risk HPV results of 1,928 patients and 13,369 cytology results of 3,306 patients. Up to 5 years after a single high-risk HPV test at 6months after treatment, AIS/CIN3+ incidence was lower in high-risk HPV negative patients (2.3%, 95%CI: 0.8-3.7) in comparison to high-risk HPV positive patients (20.1%, 95%CI: 14.2-25.5). Patients with normal cytology 6 months after treatment for AIS had a lower incidence of AIS/CIN3+ (3%, 95%CI: 2.2-3.8) in comparison to patients with low-grade (5.9%, 95%CI: 3.4-8.4) or high-grade cytology (52.1%, 95%CI: 42.7-59.9). The 5-year cumulative incidence of AIS/CIN3+ in patients testing negative for high-risk HPV consecutively at 6 and 12, 6 and 18, and 6 and 24 months was 0.6% (95% CI: 0-1.8), 1.1 (95%CI: 0-3.4), and 0% (95% CI not applicable), respectively. Similarly, for patients with consecutive normal co-tests (high-risk HPV 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 AIS/CIN3+ was 0.6% (95% CI: 0-1.8), 1.2 (95%CI: 0-3.5), and 0% (95% CI not applicable), respectively.

Conclusion: After two consecutive negative high-risk HPV or normal co-tests within 2 years after conservative AIS treatment, the risk of AIS/CIN3+ is low and it seems acceptable to refer patients back to the national cervical cancer screening program, if applicable.