九价HPV疫苗对宫颈细胞学ASC-US合并HR-HPV阳性患者的效果分析

doi:10.12092/j.issn.1009-2501.2026.04.005

中国临床药理学与治疗学 ›› 2026, Vol. 31 ›› Issue (4): 467-473.doi: 10.12092/j.issn.1009-2501.2026.04.005

九价HPV疫苗对宫颈细胞学ASC-US合并HR-HPV阳性患者的效果分析

田淑娜¹(), 施佳艳¹, 邢雅欣¹, 宁俊红²^,*(), 陈琪珍¹^,*()

1. 复旦大学附属中山医院吴淞医院妇产科，上海 200940
2. 复旦大学附属妇产科医院长三角一体化示范区青浦分院药学部，上海 201713

收稿日期:2025-09-02 修回日期:2025-10-21 出版日期:2026-04-26 发布日期:2026-04-30
通讯作者: 宁俊红,陈琪珍 E-mail:tianshuna19861106@126.com;q6155@fckqp.org.cn;qizhenchen@126.com
作者简介:田淑娜，硕士，主治医师，研究方向：妇科肿瘤。E-mail：tianshuna19861106@126.com
基金资助:
上海市卫生健康系统重点学科建设项目（2024ZDXK0068）；上海市宝山区A类重点专科资助（BSZK-2023-A02）；上海市宝山区吴淞中心医院院级课题项目（WSY202304）

Analysis of the effect of the 9-valent HPV vaccine in patients with cervical cytological ASC-US combined with HR-HPV positivity

Shuna TIAN¹(), Jiayan SHI¹, Yaxin XING¹, Junhong NING²^,*(), Qizhen CHEN¹^,*()

1. Department of Obstetrics and Gynecology, Wusong Branch, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200940, China
2. Pharmacy Department Obstetrics & Gynecology Hospital of Fudan University, Yangtze River Delta Integration Demonstration Zone (QingPu), Shanghai 201713, China

Received:2025-09-02 Revised:2025-10-21 Online:2026-04-26 Published:2026-04-30
Contact: Junhong NING,Qizhen CHEN E-mail:tianshuna19861106@126.com;q6155@fckqp.org.cn;qizhenchen@126.com

摘要/Abstract

摘要：

目的: 本研究旨在评估九价HPV疫苗对宫颈细胞学不能明确意义的非典型鳞状上皮细胞（atypical squamous cell of undetermined significance，ASC-US）合并高危型人乳头瘤病毒（high risk human papilloma virus，HR-HPV）阳性患者的病变转归及预后影响。方法: 采用前瞻性观察性队列研究设计，于2022年1月至2024年9月在复旦大学附属中山医院吴淞医院连续招募符合纳入标准的178例宫颈ASC-US合并HR-HPV阳性患者，经阴道镜病理检查分为鳞状上皮内病变组（SIL组）和宫颈炎组，其中SIL组包括低级别鳞状上皮内病变（LSIL）和高级别鳞状上皮内病变（HSIL）。SIL组经治疗后随机分为接种疫苗组和未接种疫苗组，宫颈炎组随机分为接种疫苗组和未接种疫苗组。于入组时、6个月后和12个月后比较两组的HR-HPV病毒载量及p16/Ki-67双染情况。结果: 入组时，接种疫苗组与未接种疫苗组的HR-HPV病毒载量及p16/Ki-67双染阳性率差异均无统计学意义（P>0.05）。随访6个月后，SIL组接种疫苗者的HPV16及其他12型HR-HPV病毒载量显著低于未接种疫苗组（P<0.05）；宫颈炎组接种疫苗者的HPV16病毒载量也明显低于未接种疫苗组（P<0.05）；接种疫苗组的p16/Ki-67双染阳性率均低于未接种疫苗组（P<0.05）。随访12个月后，接种疫苗组的HR-HPV病毒载量及p16/Ki-67双染阳性率均显著低于未接种疫苗组，差异均有统计学意义（P<0.05）。结论: 九价HPV疫苗的接种是预防HPV感染的有效方法，可以改善宫颈ASC-US合并HR-HPV阳性患者的预后。

关键词: HPV疫苗, ASC-US, HR-HPV, 病毒载量, p16/Ki67

Abstract:

AIM: To evaluate the effects of the nine-valent HPV vaccine on lesion progression and prognosis in patients with cervical atypical squamous cells of undetermined significance (ASC-US) combined with high-risk HPV (HR-HPV) positivity. METHODS: Using a prospective observational cohort study design, 178 eligible patients with cervical ASC-US combined with HR-HPV positivity were consecutively recruited at Wusong Hospital, affiliated to Zhongshan Hospital of Fudan University, from January 2022 to September 2024. Based on colposcopy-directed histopathology, participants were classified into a squamous intraepithelial lesion (SIL) group and a cervicitis group; the SIL group included low-grade (LSIL) and high-grade (HSIL) lesions. After completion of standard treatment, participants in each diagnostic category were randomized (1:1) to a vaccination arm or a no-vaccination (control) arm. High-risk human papillomavirus (HR-HPV) viral load and p16/Ki-67 dual-stain status were compared between arms at enrollment (baseline), 6 months, and 12 months. RESULTS: At enrollment, there were no statistically significant differences in HR-HPV viral load or p16/Ki-67 dual staining positivity rate between the vaccine and non-vaccine groups (P>0.05). At the 6-month follow-up, vaccine recipients in the SIL group exhibited significantly lower HPV16 and other 12-type HR-HPV viral loads compared to non-vaccine group (P<0.05); In the cervicitis group, vaccine recipients also had significantly lower HPV16 viral load than non-vaccine recipients (P<0.05). Moreover, the p16/Ki-67 dual staining positivity rate in the vaccine group was lower than that in the non-vaccine group (P<0.05). At the 12-month follow-up, both HR-HPV viral load and the p16/Ki-67 dual staining positivity rate in the vaccine group were significantly lower than those in the non-vaccine group, with statistically significant differences (P<0.05). CONCLUSION: Vaccination with the nine-valent HPV vaccine is an effective strategy for preventing HPV infection and can improve the prognosis in patients with cervical ASC-US and HR-HPV positivity.

Key words: HPV vaccine, ASC-US, HR-HPV, viral load, p16/Ki67

中图分类号:

田淑娜, 施佳艳, 邢雅欣, 宁俊红, 陈琪珍. 九价HPV疫苗对宫颈细胞学ASC-US合并HR-HPV阳性患者的效果分析[J]. 中国临床药理学与治疗学, 2026, 31(4): 467-473.

Shuna TIAN, Jiayan SHI, Yaxin XING, Junhong NING, Qizhen CHEN. Analysis of the effect of the 9-valent HPV vaccine in patients with cervical cytological ASC-US combined with HR-HPV positivity[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(4): 467-473.

图/表 7

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Influencing factors	Vaccinated group	Unvaccinated group	χ2 value	P value
Age (years)			1.65	>0.05
20-25	15	10
26-35	20	18
36-45	10	12
Parity			0.19	>0.05
≤2 times	35	30
>2 times	10	10
Number of sexual partners			1.29	>0.05
<3	40	32
≥3	5	8

Influencing factors	Vaccinated group	Unvaccinated group	χ2 value	P value
Age (years)			1.65	>0.05
20-25	15	10
26-35	20	18
36-45	10	12
Parity			0.19	>0.05
≤2 times	35	30
>2 times	10	10
Number of sexual partners			1.29	>0.05
<3	40	32
≥3	5	8

Influencing factors	Vaccinated group	Unvaccinated group	χ2 value	P value
Age (years)			1.75	>0.05
20-25	18	12
26-35	22	20
36-45	8	10
Parity			0.12	>0.05
≤2 times	35	32
>2 times	13	10
Number of sexual partners			0.16	>0.05
<3	36	33
≥3	12	9

Influencing factors	Vaccinated group	Unvaccinated group	χ2 value	P value
Age (years)			1.75	>0.05
20-25	18	12
26-35	22	20
36-45	8	10
Parity			0.12	>0.05
≤2 times	35	32
>2 times	13	10
Number of sexual partners			0.16	>0.05
<3	36	33
≥3	12	9

Time point	HPV type	Vaccinated group	Unvaccinated group	P value
At baseline
	HPV16	5.17±0.26	4.73±0.24	0.158
	HPV18	5.31±0.24	5.04±0.23	0.162
	Other 12 types	4.79±0.23	4.65±0.27	0.170
6 months later
	HPV16	4.43±0.26	5.01±0.3	0.042
	HPV18	4.58±0.25	4.02±0.26	0.068
	Other 12 types	4.31±0.27	5.16±0.24	0.040
12 months later
	HPV16	4.31±0.24	4.47±0.25	0.015
	HPV18	3.37±0.24	3.57±0.25	0.012
	Other 12 types	3.21±0.21	4.28±0.22	0.014

九价HPV疫苗对宫颈细胞学ASC-US合并HR-HPV阳性患者的效果分析

Analysis of the effect of the 9-valent HPV vaccine in patients with cervical cytological ASC-US combined with HR-HPV positivity

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Time point	Vaccinated group	Unvaccinated group	χ2 value	P value
At baseline	22/48	20/42	0.02	0.88
6 months later	18/48	23/42	4.25	0.04
12 months late	15/48	22/42	5.96	0.02

Time point	Vaccinated group	Unvaccinated group	χ2 value	P value
At baseline	22/48	20/42	0.02	0.88
6 months later	18/48	23/42	4.25	0.04
12 months late	15/48	22/42	5.96	0.02