Risk of residual/recurrent cervical diseases in HPV-positive women post-conization depends on HPV integration status.

Background: It is crucial to identify post-operative patients with HPV infection who are at high risk for residual/recurrent disease. This study aimed to evaluate the association between HPV integration and clinical outcomes in HPV-positive women after cervical conization, as well as to identify HPV integration breakpoints.

Methods: This retrospective study analyzed data of 791 women who underwent cervical conization for cervical intraepithelial neoplasia grades 2-3 (CIN2-3) between September 2019 and September 2023, sourced from the Fujian and Hubei cervical lesion screening cohorts. Among these, 73 women with HPV infection post-conization underwent HPV integration test within 3 months after a positive HPV test. HPV integration test was performed using the high-throughput viral integration detection (HIVID), a sensitive method for genome-wide survey of HPV integration breakpoints.

Results: Among the 73 participants with HPV infection post-conization, 10 cases (13.7%) were positive for HPV integration. The logistic regression analysis showed a higher residual/recurrent lesions risk in patients with HPV integration (OR = 3.917, p = 0.048). According to the Kaplan-Meier analysis, age ≥ 45 years (p = 0.016) and HPV integration (p = 0.035) were associated with a higher risk of residual/recurrent CIN at the 1-year follow-up. HPV 52 accounted for the majority of HPV integration genotype (3/10, 30.0%). Surprisingly, HPV 16 had the highest number of HPV average integration sequencing reads (n = 129), followed by HPV 31, 58, 52, 59, 35, and 39. The study also identified 13 HPV breakpoints, including TP63, TLR4, USP10, etc. CONCLUSIONS: HPV integration was identified as an independent risk factor for residual/recurrent CIN in HPV-positive women post-conization. Women with positive HPV integration should pay attention to careful post-treatment follow-up.