The aim of this study is to analyse the association between vaginal microbiota and the histological finding of CIN. From July 2016 until June 2017, we included 110 consecutive patients with abnormal cervical cytology results referred for colposcopy to Riga East Clinical University Hospital Outpatient department in the study group. 118 women without cervical pathology were chosen as controls. Certified colposcopists performed interviews, gynaecological examinations and colposcopies for all participants. Material from the upper vaginal fornix was taken for pH measurement and wet-mount microscopy. Cervical biopsy samples were taken from all subjects in the study group and in case of a visual suspicion for CIN in the control group. Cervical pathology was more often associated with smoking (34.6% vs. 11.0%, p < 0.0001), low education level (47.2% vs. 25.5%, p = 0.001), increased vaginal pH (48.2% vs. 25.4%, p < 0.0001), abnormal vaginal microbiota (50% vs. 31.4%, p = 0.004) and moderate to severe aerobic vaginitis (msAV) (13.6% vs. 5.9%, p = 0.049) compared to controls. The most important independent risk factors associated with CIN2+ were smoking (OR 3.04 (95% CI 1.37–6.76), p = 0.006) and msAV (OR 3.18 (95% CI 1.13–8.93), p = 0.028). Bacterial vaginosis (BV) was found more often in CIN1 patients (8/31, 25.8%, p = 0.009) compared with healthy controls (8/118, 6.8%), or CIN2+ cases (8/79, 10.1%). In the current study msAV and smoking were the most significant factors in the development of CIN in HPV-infected women, especially high grade CIN. We suggest that AV changes are probably more important than the presence of BV in the pathogenesis of CIN and progression to cervix cancer and should not be ignored during the evaluation of the vaginal microbiota.

Elevated vaginal pH is associated with different types of abnormal vaginal flora and the presence of sperm cells.

No abstract

Summary Introduction. Cervical cancer is the fourth most common form of cancer in women [19]. The precancerous stages are divided into three distinctive stages, labelled cervical intraepithelial neoplasia (CIN) I, II and III. One of the aetiological factors is chronic inflammation in cervical tissue, most often induced by Human papilloma virus (HPV). 88,5% of the patients regress from low grade intraepithelial changes to unchanged epithelium [14]. It has been proposed that cytokine balance plays a key role in the development of high grade epithelial changes (CIN I – CIN III) in the remaining 11.5% of patients, however, the exact trigger of this event remains to be found. Aim of the Study. The aim of the study was to determine three pro-inflammatory (IL-1α, IL-6, IL-8) and one anti-inflammatory (IL-10) interleukin expression in different CIN cervix uteri biopsies. Material and methods. 16 biopsies were obtained with different CIN staging: one with CIN I stage, five with CIN II stage and 10 with CIN III stage. The samples were stained with haematoxylin and eosin and immunohistochemistry for IL-1α, IL-6, IL-8 and IL-10. Slides were evaluated semi-quantitatively grading the intensity of positively stained structures in the visual field. Results. Examination of the samples yielded the following: IL-1α expression increased from CIN II to CIN III in squamous epithelium, while IL-8 expression decreased. A few IL-1α containing inflammatory cells were found in all CIN stages. IL-8 expression in subepithelium and the number of inflammatory cells decreased from CIN II stage to CIN III, although, it increased in the blood vessel endothelium. Conclusions. There was constant moderate expression of both IL-6 and IL-10 during all CIN stages, except for inflammatory cells, where IL-6 expression was high during all stages, yet there were few IL-10 containing cells during CIN. The balanced expression of both cytokines suggests that pro- and anti-inflammatory cytokine balance has an important role in CIN morfopathogenesis. The high expression of IL-6 in inflammatory cells and constant expression trough CIN staging indicates sustentation of chronic inflammation and production of other cytokines, such as IL-8, IL-1α. The variable IL-8 expression and its decrease in CIN III stage suggests the depletion of IL-8 production. The high expression of cytokines in blood vessel endothelium indicates their important role in CIN morfopathogenesis.