The Correlation Of Vaginal Microenvironment Multifactorial Changes And Cervical Intraepithelial Neoplasia

Objective:To study the vaginal flora, p H value and cytokines(IL-2, IL-10, CCL22) in vaginal washing fluid of patients with different grade of cervical intraepithelial neoplasia and people with normal cervical biopsy, then to analysis their impact on cervical intraepithelial neoplasia, and to explore the relationship between CIN lesion and emblance of vaginal microecosystem as well as local immune factors, hoping to provide an experimental basis for improving vaginal immune status, and discovery the potential biological indicators for CIN lesion, and provide novel findings for the prevention and treatment of cervical cancer.Methods:Individuals for health physical examination at maternal and child care service centre of jiexiu, shanxi of married women 20-65 years for the survey, from June 2014 to December 2014 were enrolled. In total 174 patients(CINⅠ137cases, CINⅡ/Ⅲ 37cases)diagnosed with CIN by biopsy were recruited, take 193 normal samples as control group.TCT was performed on all of them first, The vaginal p H was tested by short range p H paper. Vaginal discharge was examined under a microscope in a drop of 0.9% saline solution to check for trichomonads. detect for Candida spp or clue cells by Gram Stain and HPV-DNA by using PCR and Membrane hybridization technique for those who were diagnosed with ASCUS and above, take cervical tissues by using electron colposcope,get inflammatory factors(IL-2, IL-10, CCL-22)tested by enzyme-linked immunosorbent assay(ELISA).Results:1. HR-HPV detection in cervical exfoliated cells: With the increase of cervical lesion degree, HR-HPV infection rate increased gradually, CINⅡ/Ⅲ group is higher than the control group and CINⅠgroup(P < 0.001). While CIN I have no statistical difference with the control group.2. Micro-ecological detection in vaginal secretion: Vaginal p H value has comparative statistically significant differences among the control group, CINⅠgroup and CINⅡ/Ⅲgroup, the p H value in CINⅠgroup and CINⅡ/Ⅲ group are higher than control group(P< 0.001), while CINⅠgroup and CINⅡ/Ⅲ have no statistically significant differences. In addition, the incidence ratio of vaginal microbial flora disorder(including bacterial vaginal disease, trichomonas vaginitis, and vulva vagina candida disease) have no statistically significant difference in the control group, CINⅠgroup and CINⅡ/Ⅲ group.3.Immune cytokine detection in vaginal lavage: the expression of IL-10 has comparative statistically significant differences between the control group, CIN Ⅰ group and CINⅡ/Ⅲgroup. In the control group, among them, IL–10 in CINⅠgroup and CINⅡ/Ⅲgroup are significently lower than control group, while CINⅠgroup and CINⅡ/Ⅲhave no statistically significant differences. In addition, the expression level of CCL22 and IL-2 have no statistically significant difference in the control group, CINⅠ group and CINⅡ/Ⅲ group.4.The high-risk factors of CIN Ⅱ / Ⅲ :In multinomial logistic regression analysis,taking CIN II/III as control group, comparing with normal people, HPV negative resulting in CINⅡ/Ⅲ was 0.067 times as those HPV positive, elevated p H value resulting in CINⅡ/Ⅲ was 6.934 times as those normal p H value, IL-10<400 resulting in CINⅡ/Ⅲwas 4.115 times as those IL-10>400. Taking CINⅡ/Ⅲ as control group,comparing with CINI group,HPV negative resulting in CINⅡ/Ⅲ was 0.086 times as those HPV positive, elevated p H value resulting in CINⅡ/Ⅲ was 4.887 times as those normal p H value.Conclusion:1.Cervical intraepithelial neoplasia are associated with incrased HR-HPV infection,in the high grade CIN lesions, infection rates were significantly higher.2.Eelevated p H value are risk factors for CIN and the development of precursor lesions. An elevated vaginal p H may promote the development of CIN, but have no significant relationship with the degree of lesion. Vaginal microecological imbalance may be a risk factor for cervical lesions.Infection of human papillomavirus and elevated p H value are risk factors for CIN and the development of precursor lesions.3.The reduce of IL-10 is the early event for CIN. We can collect the vaginal lavage and detect the expression of IL-10, which can work as the biological indicators for CIN diagnosis.