Li Li, Ding Ling, Gao Tao, Lyu Yuanjing, Wang Ming, Song Li, Li Xiaoxue, Gao Wen, Han Yang, Jia Haixia, Wang Jintao
Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan, China.
Department of Preventive Medicine, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago 60611, USA.
J Cancer. 2020 Jan 1;11(2):284-291. doi: 10.7150/jca.35022. eCollection 2020.
There are other factors that contribute to cervical carcinogenesis except HPV infection. This study aimed to investigate the association between vaginal micro-environment factors, including HO, vaginal PH value, vagina cleanness, β-glucuronidase, coagulase, neuraminidase and leukocyte esterase and cervical intraeipithelial neoplasia (CIN). In total 1019 participants, including 623 normal cervical (NC) women, 303 patients with low-grade cervical intraepithelial neoplasia (CIN1) and 93 patients with high-grade cervical intraepithelial neoplasia (CIN2/3), were enrolled into the study. HPV genotyping was detected by flow-through hybridization and gene chip. Vaginal HO, β-glucuronidase, coagulase, neuraminidase and leukocyte esterase were detected by Aerobic Vaginitis (AV) / Bacterial Vaginal Disease (BV) Five Joint Test Kit. Vaginal PH was measured on the glass slide after microscopy, using color strips with a PH range of 3.8-5.4. Vagina cleanness was determined according to the National Clinical Laboratory Practice Guideline. test and Logistic regression were operated using SPSS 22.0 software. Our results showed that HPV16 infection rate and the abnormal rates of HO, PH, vagina cleanness, β-glucuronidase or neuraminidase increased gradually along with the severity of CIN (<0.05). Abnormities of HO, cleanness, β-glucuronidase and neuraminidase were risk factors for CIN regardless of HPV16 infection, furthermore, abnormities of PH value, leukocyte esterase could also increase the risk of CIN in HPV16 positive group. In addition, women with abnormal vaginal micro-environment factors in HPV16 positive group had a significantly higher risk of developing CIN than HPV16 negative group. The results from generalized multifactor dimensionality reduction (GMDR) model showed that there was interaction effect with abnormities of vagina cleanness, HO, β-glucuronidase and neuraminidase on CIN2/3 in HPV16 negative group, while, there was interaction effect with abnormities of vagina cleanness, β-glucuronidase and neuraminidase on CIN1 and with abnormities of vagina cleanness, PH, HO, β-glucuronidase, neuraminidase and leukocyte esterase on CIN2/3 in HPV16 positive group. Our results suggested that vaginal micro-environment disorder could increase the risk of CIN, especially, the abnormality of HO, cleanness, β-glucuronidase and neuraminidase. There were interaction effects with abnormities of HO, vagina cleanness, β-glucuronidase and neuraminidase on CIN whether HPV16 was infected or not.
除人乳头瘤病毒（HPV）感染外，还有其他因素会导致宫颈癌的发生。本研究旨在调查阴道微环境因素，包括过氧化氢（HO）、阴道pH值、阴道清洁度、β-葡萄糖醛酸酶、凝固酶、神经氨酸酶和白细胞酯酶与宫颈上皮内瘤变（CIN）之间的关联。共有1019名参与者纳入本研究，其中包括623名宫颈正常（NC）女性、303名低度宫颈上皮内瘤变（CIN1）患者和93名高度宫颈上皮内瘤变（CIN2/3）患者。采用导流杂交和基因芯片技术检测HPV基因分型。采用需氧性阴道炎（AV）/细菌性阴道病（BV）五联检测试剂盒检测阴道HO、β-葡萄糖醛酸酶、凝固酶、神经氨酸酶和白细胞酯酶。显微镜检查后，在载玻片上用pH范围为3.8 - 5.4的色带测量阴道pH值。根据国家临床检验操作规程确定阴道清洁度。使用SPSS 22.0软件进行检验和Logistic回归分析。我们的结果显示，随着CIN严重程度的增加，HPV16感染率以及HO、pH值、阴道清洁度、β-葡萄糖醛酸酶或神经氨酸酶的异常率逐渐升高（P<0.05）。无论HPV16感染情况如何，HO、清洁度、β-葡萄糖醛酸酶和神经氨酸酶的异常都是CIN的危险因素，此外，pH值、白细胞酯酶的异常在HPV16阳性组中也会增加CIN的风险。此外，HPV16阳性组中阴道微环境因素异常的女性发生CIN的风险显著高于HPV16阴性组。广义多因素降维（GMDR）模型结果显示，在HPV16阴性组中，阴道清洁度、HO、β-葡萄糖醛酸酶和神经氨酸酶异常对CIN2/3存在交互作用，而在HPV16阳性组中，阴道清洁度、β-葡萄糖醛酸酶和神经氨酸酶异常对CIN1存在交互作用，阴道清洁度、pH值、HO、β-葡萄糖醛酸酶、神经氨酸酶和白细胞酯酶异常对CIN2/3存在交互作用。我们的结果表明，阴道微环境紊乱会增加CIN的风险，尤其是HO、清洁度、β-葡萄糖醛酸酶和神经氨酸酶的异常。无论是否感染HPV16，HO、阴道清洁度、β-葡萄糖醛酸酶和神经氨酸酶异常对CIN均存在交互作用。
