宫颈锥切术后高危型人乳头瘤病毒持续感染的高危因素

doi:10.16150/j.1671-2870.2024.04.010

摘要/Abstract

摘要：

目的：分析宫颈锥形切除术后高危型人乳头瘤病毒（high-risk human papillomavirus，HR-HPV)持续感染的高危因素，从而识别宫颈锥切术后宫颈病变残留、复发高危人群。方法：收集2017年1月1日至2022年5月31日期间术前至少有1种HR-HPV阳性，且在我院门诊或病房行宫颈锥切手术的患者共467例。将宫颈锥切术后6个月内HR-HPV阳性者纳入HR-HPV持续感染组，HR-HPV阴性者纳入HR-HPV清除组。比较2组间的年龄、绝经状态、术前HR-HPV感染情况、术前液基薄层细胞学（thinprep cytologic test，TCT)、宫颈活检病理级别、锥切切缘状态、是否累腺、锥切手术的方式等差异。其中，年龄差异比较采用秩和检验，其他指标比较采用卡方检验。采用多因素Logistic回归分析，寻找宫颈锥切术后HR-HPV持续感染的高危因素。结果：宫颈锥切术后6个月内HR-HPV清除率为64.0%。年龄≥46岁（P<0.001）、绝经（P<0.001）、术前存在HPV 16、HPV 52、HPV 58中任一型别感染者（P=0.002）、术前多重HR-HPV感染者（P<0.001）、术前TCT<高级别上皮内瘤变（high-grade squamous intraepithelial lesion，HSIL)（P=0.005）、宫颈活检病理<HSIL（P=0.020）、切缘不净（P=0.003）、累及腺体（P=0.008）或采用宫颈环形电切术(loop electrosurgical excision procedure, LEEP)（P<0.001）者，在宫颈锥切术后发生HR-HPV持续感染的概率更高。多因素Logistic回归分析显示，绝经（OR=3.453, P<0.001）、术前HR-HPV多重感染（OR=2.683, P<0.001）、术前TCT<HSIL（OR=1.884, P=0.015）、切缘不净（OR=1.479, P=0.048）以及采用LEEP术式（OR=2.330, P=0.013），是宫颈锥切术后HR-HPV持续感染的独立危险因素。锥切术后6~24个月宫颈病变的残留、复发率为12.2%，相较于HR-HPV清除组，术后HR-HPV持续感染组在宫颈锥切术后6~24个月发生宫颈病变残留、复发的风险更高（28.6%比3.0%，χ²=65.585, P<0.001），宫颈残留、复发病变的病理级别为HSIL的风险亦更高（Fisher检验， P=0.027）。结论：本研究纳入较大样本量，识别出绝经、术前HR-HPV多重感染、术前TCT<HSIL、切缘不净、采用LEEP术式者是宫颈锥切术后HR-HPV持续感染的高危人群，此类人群术后发生宫颈病变（特别是HSIL病变）残留、复发风险更高。

关键词: 高危型人乳头瘤病毒, 宫颈病变, 宫颈癌, 子宫颈锥形切除术

Abstract:

Objective To analyze the risk factors of persistent infection of high-risk human papillomavirus (HR-HPV) after cervical conization, so as to identify the high-risk population of residual and recurrent cervical lesions after cervical conization. Method A total of 467 patients with one more HR-HPV infection and underwent cervical conization in the outpatient clinic and ward of our hospital from January 1,2017 to May 31,2022 were collected. After cervical conization,HR-HPV-positive patients within 6 months were included in the HR-HPV persistent infection group, and HR-HPV-negative patients were included in the HR-HPV clearance group. The differences in age, menopausal status, preoperative HR-HPV infection, preoperative thinprep cytologic test (TCT), pathological grade of cervical biopsy, conization margin status, glandular involvement, and conization surgery were compared between the two groups. Among them, the age difference was processed by rank sum test, and other indicators were compared by chi-square test. Multivariate Logistic regression analysis was used to find the high risk factors for HR-HPV persistent infection after cervical conization. Result The HR-HPV clearance rate was 64.0% within 6 months after cervical conization. Patients with age ≥ 46 years old (P<0.001 ), menopause (P<0.001), preoperative infection of any type of HPV 16, HPV 52 or HPV 58 (P=0.002), preoperative multiple HPV infection (P<0.001), preoperative TCT < high grade squamous intraepithelial lesion (HSIL) (P=0.005), cervical biopsy pathology < HSIL (P=0.020), unclean margin (P=0.003), gland involvement (P=0.008) or loop electrosurgical excision procedure (LEEP) (P<0.001), had a higher probability of HR-HPV persistent infection after cervical conization. Multivariate Logistic regression analysis showed that menopause (OR=3.453, P<0.001), preoperative HR-HPV multiple infection (OR=2.683, P<0.001), preoperative TCT < HSIL (OR=1.884, P=0.015), unclean margin (OR=1.479, P=0.048) and LEEP (OR=2.330, P=0.013) were independent risk factors for HR-HPV persistent infection after cervical conization.The residual and recurrence rate of cervical lesions at 6-24 months after conization was 12.2%. Compared with HR-HPV clearance group, HR-HPV persistent infection group had a higher rate of residual and recurrent cervical lesions at 6-24 months after cervical conization (28.6% vs 3.0%, χ²=65.585, P<0.001), and the risk of HSIL was also higher (Fisher test, P=0.027). Conclusions In this study, a large sample size is included, and menopause, preoperative HR-HPV multiple infection, preoperative TCT < HSIL, unclean margin, and LEEP are identified as high-risk factors for HR-HPV persistent infection after cervical conization, and a higher risk of residual and recurrent cervical lesions (especially HSIL lesions) after cervical conization.

Key words: High-risk human papillomavirus, Cervical lesions, Cervical cancer, Cervical conization

中图分类号:

R711.74

付溪娜, 许新, 李天杰, 金影. 宫颈锥切术后高危型人乳头瘤病毒持续感染的高危因素[J]. 诊断学理论与实践, 2024, 23(04): 416-423.

FU Xina, XU Xin, LI Tianjie, JIN Ying. Study on the risk factors for persistent infection of high-risk human papillomavirus after cervical conization[J]. Journal of Diagnostics Concepts & Practice, 2024, 23(04): 416-423.

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Before surgery	Status	HR-HPV after conization		χ²	P
Before surgery	Status	Persistent infection group (n=168)	Clearance group (n=299）	χ²	P
HPV 16 / 18 infection before surgery	Yes	80（47.6）	159（53.2）	1.330	0.249
	No	88（52.4）	140（46.8）
Any type of HPV 16,52 or 58 infection	Yes	71（42.3）	85（28.4）	9.253	0.002
	No	97（57.7）	214(71.6)
HR-HPV infection	Single type	78（46.4）	194（64.9）	15.062	<0.001
	Multiple type	90（53.6）	105（35.1）

Variation		HR-HPV persitent infection group (n=168)	HR-HPV after conization clearnce group (n=299）	χ²	P
Menopause	No	104（29.1）	254（70.9）	31.926	<0.001
	Yes	64(58.7)	45（41.3）
TCT	<HSIL	139（82.7）	212（70.9）	8.070	0.005
	≥HSIL	29（17.3）	87（29.1）
Pathological biopsy	<HSIL	28（16.7）	28（9.4）	5.435	0.020
	≥HSIL	140（83.3）	271（90.6）
Margin	Clean	137（81.5）	272（91.0）	8.779	0.003
	Nnclean	31(18.5)	27(9.0)
Glands involvement	Yes	91（54.2）	124（41.5）	6.978	0.008
	No	77（45.8）	175（58.5）
Surgery	LEEP	155（92.3）	238（79.6）	12.935	<0.001
	CKC	13（7.7）	61（20.4）

Variation	Single factor analysis		Multiple factor analysis
Variation	OR(95%CI)	P	OR（95%CI）	P
Menopause	3.474（2.227~5.417）	<0.001	3.453（2.146~5.555）	<0.001
Any type of HPV16,52 or 58 infection before surgery	1.843（1.240~2.738）	0.002
Multiple type of HR-HPV infection before surgery	2.887（1.993~4.182）	<0.001	2.683（1.825~3.944）	<0.001
TCT<HSIL	1.967（1.227~3.152）	0.005	1.884（1.130~3.142）	0.015
Pathological biopsy<HSIL	3.056（1.624~5.749）	0.001
Glands	1.668（1.140~2.441）	0.008
Margin clean	1.675（1.169~2.398）	0.005	1.479（1.003~2.181）	0.048
LEEP	3.056(1.624~5.749)	0.001	2.330（1.193~4.551）	0.013