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高危型人乳头瘤病毒（High-risk human papillomavirus, HR-HPV）持续感染是诱发宫颈癌的，但其载量与相关分子机制及宫颈癌病变的关系尚未明确。Hipp0-YAP信号通路的关键分子为Hipp0-Yes相关蛋白1(YAP1)，其表达异常可导致Hipp0-YAP调节异常，诱导肿瘤形成。为阐明HR-HPV感染在Hipp0-YAP通路调节及宫颈癌发病中的作用，本研究分析了HR-HPV载量与Hipp0-YAP通路及宫颈癌病变的关系。首先检测宫颈癌患者、宫颈上皮内瘤变（CIN）患者及子宫良性病变患者HR-HPV感染及YAP1表达情况，分析HR-HPV载量与YAP1的关系、HRHPV感染和YAP1阳性与CIN分级和宫颈癌患者临床特征的关系；然后以CIN及宫颈癌患者中HR-HPV阴性表达为参照，采用单因素Logistic模型分别分析HR-HPV感染与宫颈癌病变的关系及HR-HPV载量与宫颈癌病变的关系。结果显示，宫颈癌组、CIN组HR-HPV感染率及YAP1阳性率均高于对照组，宫颈癌组HR-HPV感染率及YAP1阳性率高于CIN组（P<0.05）,CIN Ⅲ期及CIN Ⅱ期患者HR-HPV感染率、YAP1阳性率均高于CIN Ⅰ期患者（P<0.05），且宫颈癌患者HR-HPV感染率与分化程度、FIGO分期、淋巴结转移有关，YAP1表达情况与FIGO分期、淋巴结转移有关（P<0.05）;HR-HPV载量与YAP1表达呈正相关（P<0.05）;HR-HPV单一感染和多重感染均可增加CIN患病风险，且多重感染可增加宫颈癌风险；中、高HR-HPV载量可增加宫颈癌患病风险，低、中、高HRHPV载量均可增加CIN患病风险。以上结果表明，HR-HPV载量与YAP1表达呈正相关，高HR-HPV载量可增加宫颈癌病变风险。
Abstract：Persistent infection with high-risk human papillomavirus(HR-HPV) is a major cause of cervical cancer, however, the relationship between its viral load, associated molecular mechanisms, and cervical cancer lesions remains unclear. The key molecule in the Hipp0-YAP signaling pathway is Hippo-Yes-associated protein1(YAP1), whose abnormal expression can disrupt Hippo-YAP regulation and promote tumor formation. To elucidate the role of HR-HPV infection in regulating the Hipp0-YAP pathway and the development of cervical cancer, this study analyzed the relationship between HR-HPV load, YAP1 expression, and cervical cancer lesions. First, HR-HPV infection and YAP1 expression were assessed in patients with cervical cancer, cervical intraepithelial neoplasia(CIN), and benign uterine lesions. The relationship between HR-HPV load and YAP1 expression, as well as the correlation between HR-HPV infection, YAP1 positivity, CIN grade, and clinical characteristics of cervical cancer patients, was analyzed. Next, using HR-HPV negative expression in CIN and cervical cancer patients as a reference, a univariate logistic regression model was employed to analyze the relationship between HR-HPV infection and cervical cancer lesions, as well as the relationship between HR-HPV load and cervical cancer lesions. The results indicated that the HR-HPV infection rate and YAP1 positivity rate were higher in the cervical cancer and CIN groups compared to the control group, with the cervical cancer group showing significantly higher rates than the CIN group(P < 0.05).Additionally, the HR-HPV infection rate and YAP1 positivity rate were higher in CIN Ⅲ and CIN Ⅱ patients than in CIN Ⅰ patients(P < 0.05). In cervical cancer patients, HR-HPV infection was associated with degree of differentiation, FIGO stage, and lymph node metastasis, while YAP1 expression correlated with FIGO stage and lymph node metastasis(P < 0.05). HR-HPV load was positively correlated with YAP1 expression(P <0.05). Both single and multiple HR-HPV infections increased the risk of CIN, with multiple infections further increasing the risk of cervical cancer. Medium and high HR-HPV loads were found to elevate the risk of cervical cancer, while all levels of HR-HPV load(Low, medium, and high) were associated with an increased risk of CIN. These findings suggest that HR-HPV load is positively correlated with YAP1 expression, and that high HR-HPV load can increase the risk of cervical cancer lesions.
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基本信息:
DOI：10.13242/j.cnki.bingduxuebao.240277
中图分类号:R737.33
引用信息:
[1]徐燕,申晓娟,李姗姗.高危型人乳头瘤病毒载量与Hipp0-YAP通路蛋白表达水平及宫颈癌病变的关系研究[J].病毒学报,2025,41(04):1196-1202.DOI:10.13242/j.cnki.bingduxuebao.240277.
基金信息:
盐城市卫生健康委科研项目（项目号：YK2023135）,题目：花粉薏仁汤治疗湿热下注型宫颈HPV感染的临床研究~~
2024-11-20
2024
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2025-06-04
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