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.

Objectives The aims of the study were to find out why some post-reproductive aged women did not participate in the organised cervical cancer screening programme in Latvia and to clarify factors that would motivate them to take part. Methods A cross-sectional study was carried out between January and July 2017 among female patients in three general practitioner (GP) practices. GP practice nurses used the Latvian national health service database to identify women aged 25-70 who had not participated in the organised programme for the last 3 years. Participants were asked to complete a specially developed questionnaire. The results were then compared between three age groups: 25-34, 35-49 and 50-70 years. Results Included in the study were 523 out of 992 women who had not attended screening; 41% were in the age group 50-70 years. Post-reproductive aged women statistically significantly more often did not take part in the programme because of lack of time (26.4%), too great a distance to the gynaecology screening clinic (10.4%), lengthy appointment waiting time (8.5%) and a belief that a smear test was unnecessary for them (8.5%); 32.1% of women in this age group indicated that if the cervical screen could be carried out by their GP it would facilitate their participation in the programme. Conclusion Post-reproductive aged women in Latvia often do not attend cervical cancer screening. Analysis of personal and organisational barriers confirmed that the involvement of GPs would encourage older women to participate in the organised screening programme.

High-risk human papillomavirus infection (HR-HPV) is necessary but not the only factor needed to develop cervical cancer. It is essential to estimate cervical cancer development risk in the population of high-risk HPV-positive women and to avoid unnecessary examinations and treatment in low-risk individuals. The study aimed to identify associations between different personal factors, vaginal microflora, sexually transmitted, high-risk HPV infection, and various degrees of cervical precancerous lesions. A study was performed in 2016–2020. The study group consisted of 112 patients with abnormal cervical cytology results referred for colposcopic examination. 120 women who came for a routine gynecological check-up were included in the control group. Material from the cervix and upper vaginal fornix was taken for pH measurement, wet mount microscopy, testing the six most common high-risk HPV DNA types (16/18, 31, 33, 45, 58), HPV E6/E7 mRNA, and 7 genital infections–C. trachomatis, N. gonorrhea, T. vaginalis, M. hominis, M. genitalium, U. urealyticum, U. parvum. Results showed that women with all grades of cervical intraepithelial neoplasia (CIN) more often were smokers, had increased vaginal pH levels, and had positive HR-HPV DNA and HR HPV E6/E7 mRNA expression. Abnormal vaginal microflora, especially types associated with aerobic vaginitis, and M. hominis were significantly more often found in women with CIN2+. The presence of C.trachomatis, U. parvum, and U.urealyticum did not differ between the groups. The most important factors independently associated with CIN2+ were positive high-risk HPV E6/E7 mRNA expression (OR 59.4, 95% CI 14.84–237.51), and positive high-risk HPV DNA (OR 3.9, 95% CI 1.16–13.23). Higher education level was associated with reduced risk of CIN2+ (OR 0.2, 95% CI 0.07–0.71). In conclusion, this study reports HR-HPV DNA of the most common six types and E6/E7 mRNA positivity as the most significant factors associated with CIN2+ lesions and higher education related to lower risk of high-grade cervical lesions.

Cervical cancer remains a significant public health challenge, particularly in regions where prevention programmes have not achieved optimal effectiveness. While persistent high-risk human papillomavirus infection is a necessary cause of cervical neoplasia, disease progression is influenced by a complex interplay of viral, host, microbial, and behavioural factors. This study aimed to identify associations between various social factors, the vaginal ecosystem, vaginal infections, including sexually transmitted infections and high-risk human papillomavirus, human leucocyte antigen (HLA) class II alleles, and different degrees of cervical precancerous changes. The study group included 112 consecutive new patients referred to Riga East University Hospital for colposcopy examination due to abnormal cervical cytology smear results. The control group consisted of 120 women who underwent a gynaecological examination for other reasons (routine examination, follow-up of other gynaecological pathology). All patients included in the study were interviewed, and a custom-designed questionnaire was filled out. After that, women had gynaecological examination, pH measurement of vaginal discharge; samples were taken for wet-mount microscopy, testing of HPV DNA, mRNA, vaginal infections, and HLA class II genes. As a next step, a colposcopy was performed, and biopsies were taken if indicated. The study revealed that smoking is a significant independent risk factor for CIN2+, whereas higher educational attainment has a protective effect. Disturbances of vaginal ecosystem, including elevated pH and abnormal microflora, were more common among women with cervical neoplasia. Specifically, bacterial vaginosis was linked to low-grade lesions. At the same time, aerobic vaginitis – exceptionally moderate to severe cases – demonstrated a strong, independent association with high-grade cervical lesions (CIN2+), highlighting the critical role of vaginal inflammation in cervical carcinogenesis. Detection of HR-HPV DNA and E6/E7 mRNA emerged as the most important predictors of high-grade cervical lesions. Although no significant associations were found between sexually transmitted infections and CIN, Mycoplasma hominis ranked as the third most important independent risk factor for CIN2+. Genetic analysis identified significant associations between specific HLA class II alleles (HLA-DRB1*11:01, DRB1*15:01, DQA1*01:03, DQA1*04:01, DQB1*03:01, and DQB1*04:01) and an increased risk of CIN2+, while other alleles (DRB1*14:01, DRB1*16:01, and DQA1*03:01) appeared to confer a protective effect. The findings underscore the limitations of universal, one-size-fits-all screening strategies and highlight the urgent need for personalised, risk-based cervical cancer prevention models that integrate viral, microbial, genetic, and epidemiological risk factors. Such individualised approaches could improve screening precision, resource allocation, and ultimately contribute to the elimination of cervical cancer as a public health concern. The Doctoral Thesis was developed at the Department of Obstetrics and Gynaecology of Rīga Stradiņš University and the Outpatient Department of Riga East University Hospital. Defence of the Doctoral Thesis will take place at the public session of the Promotion Council of Clinical Medicine on 23 of September 2026 at 13.00 in the Hippocrates Lecture Theatre, 16 Dzirciema iela, Rīga Stradiņš University. The Doctoral Thesis was developed with the support of the project “Research of clinical and molecular characteristics of cervical cancer research to improve the early diagnostics and treatment strategy” No.: RSU ZP 04/2013. 3.2. Clinical Medicine; Sub-Sector – Obstetrics and Gynaecology. Keywords: cervical intraepithelial neoplasia; high-risk human papillomavirus; personalised screening.