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锥切术后HPV阳性女性残留/复发性宫颈疾病的风险取决于HPV整合状态。

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

作者信息

Lin Wenyu, Huang Yuxuan, Zhang Yan, Huang Lixiang, Cai Hongning, Huang Guanxiang, Li Ye, Zhang Qiaoyu, Xue Huifeng, Dong Binhua, Sun Pengming

机构信息

College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, 350001, China.

Fujian Key Laboratory of Women and Children's Critical Diseases Research, Fujian Maternity and Child Health Hospital (Fujian Women and Children's Hospital), Fuzhou, Fujian, 350001, China.

出版信息

Infect Agent Cancer. 2025 Jan 28;20(1):5. doi: 10.1186/s13027-025-00637-3.

DOI:10.1186/s13027-025-00637-3
PMID:39875925
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11773928/
Abstract

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.

摘要

背景

识别术后HPV感染且有残留/复发疾病高风险的患者至关重要。本研究旨在评估HPV整合与宫颈锥切术后HPV阳性女性临床结局之间的关联,并确定HPV整合断点。

方法

这项回顾性研究分析了2019年9月至2023年9月期间来自福建和湖北宫颈病变筛查队列的791例因宫颈上皮内瘤变2-3级(CIN2-3)接受宫颈锥切术的女性的数据。其中,73例锥切术后HPV感染的女性在HPV检测呈阳性后3个月内接受了HPV整合检测。HPV整合检测采用高通量病毒整合检测(HIVID),这是一种用于全基因组范围内调查HPV整合断点的灵敏方法。

结果

在73例锥切术后HPV感染的参与者中,10例(13.7%)HPV整合呈阳性。逻辑回归分析显示,HPV整合患者残留/复发病变的风险更高(OR = 3.917,p = 0.048)。根据Kaplan-Meier分析,年龄≥45岁(p = 0.016)和HPV整合(p = 0.035)与1年随访时残留/复发CIN的较高风险相关。HPV 52占HPV整合基因型的大多数(3/10,30.0%)。令人惊讶的是,HPV 16的HPV平均整合测序读数数量最高(n = 129),其次是HPV 31、58、52、59、35和39。该研究还确定了13个HPV断点,包括TP63、TLR4、USP10等。结论:HPV整合被确定为宫颈锥切术后HPV阳性女性残留/复发CIN的独立危险因素。HPV整合阳性的女性应注意仔细的术后随访。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef2a/11773928/e5da90d8a32d/13027_2025_637_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef2a/11773928/b61bae4d5fe3/13027_2025_637_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef2a/11773928/2b0ce765d64e/13027_2025_637_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef2a/11773928/0f32beb8dbd9/13027_2025_637_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef2a/11773928/e5da90d8a32d/13027_2025_637_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef2a/11773928/b61bae4d5fe3/13027_2025_637_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef2a/11773928/2b0ce765d64e/13027_2025_637_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef2a/11773928/0f32beb8dbd9/13027_2025_637_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef2a/11773928/e5da90d8a32d/13027_2025_637_Fig4_HTML.jpg

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