Značilnosti okužb s človeškimi papilomavirusi po uvedbi cepljenja proti raku materničnega vratu
Year: 2026
Type: dissertation
Study design: Observational Study
Abstract: Introduction The main aetiological factor in the development of cervical cancer is long-term, persistent infection with high-risk human papillomavirus (HPV) types. Due to HPV being a necessary, though not exclusive, causal factor, cervical cancer is unique among human malignancies, as it can be effectively prevented and potentially eliminated through coordinated public health interventions. According to European guidelines for quality assurance in cervical cancer screening, HPV testing is advocated as the primary screening method. However, these guidelines also emphasise the importance of evaluating local epidemiological conditions, particularly HPV prevalence, before transitioning from successful cytology-based screening programmes to HPV-based screening. The Slovenian organised, population-based National Cervical Cancer Screening Programme (NCCSP) for early detection of precancerous lesions and cervical cancer provides triennial cytological screening (Pap tests) for women aged 20–64 years. Since its establishment in 2003, the programme has consistently achieved screening coverage exceeding 70%, and cervical cancer incidence in Slovenia has been reduced by half. However, in the last decade, the cervical cancer incidence has plateaued, highlighting the need to optimise preventive strategies in the era of HPV vaccination. In 2009–2010, the first nationwide cross-sectional survey was carried out to assess cervical HPV prevalence prior to the implementation of school-based HPV vaccination programme in Slovenia. The study included over 4,400 Slovenian women aged 20–64 years participating in routine NCCSP screening. The overall prevalence of cervical infections with 14 HPV types prior to vaccination was estimated at 13.3%, as determined using the clinically validated Alinity m HR HPV Assay, which was also employed in the present study. In the same period, during the 2009/2010 school year, HPV vaccination was introduced into the national immunisation programme for girls in the 5th–6th grades of primary school (ages 11–12), offering free vaccination with three doses of the quadrivalent HPV vaccine. The first seven birth cohorts of women who had the opportunity to receive HPV vaccination through this national school-based programme were aged 20–27 at the time of the present study and had entered the NCCSP screening programme, providing a unique opportunity to evaluate the real-time population impact of HPV vaccination on cervical HPV prevalence in Slovenia. Studies from Western, Northern, and Southern Europe report significant reductions in cervical HPV prevalence following vaccination. conversely, data from Central and Eastern European countries remain limited and methodologically less robust, hindering straightforward comparison with findings from Western and Northern Europe. To the best of our knowledge, this is the first and largest study in the region to assess HPV vaccination effectiveness and associated population-level effects, including herd immunity, cross-protection, and potential genotype replacement. It is also the first study in Central and Eastern Europe with methodologically consistent comparison of cervical HPV prevalence before and after the implementation of a national school-based HPV vaccination programme. Methods We conducted a prospective cross-sectional study enrolling Slovenian women aged 20–64 years attending routine gynaecological screening visits within the NCCSP from December 2023 to March 2025 at 21 participating gynaecological practices throughout Slovenia. Eligible participants included women with a normal Pap result in the previous screening round or women undergoing their first cervical sampling upon programme entry. Exclusion criteria were pregnancy, menstruation, colpitis or cervicitis, hysterectomy, conditions preventing adequate cervical sampling, follow-up smears after pathological results, post-treatment smears, or suspected malignancy. All participants provided written informed consent. The study was approved by the National Medical Ethics Committee of Slovenia (consent number 0120-218/2023/10). Cervical specimens for HPV testing were obtained using a CervexBrush (Rovers Medical Devices, Oss, the Netherlands) and stored in ThinPrep PreservCyt Solution (Hologic Inc., Marlborough, MA, USA). Gynaecologists documented participants’ HPV vaccination status on a standardised form, while participants completed an anonymous questionnaire confirming their HPV vaccination history. All samples and data were anonymised using unique codes. Cervical specimens were tested using the clinically validated Alinity m HR HPV Assay (Abbott Molecular, Des Plaines, IL, USA) on the automated Alinity m system according to manufacturer instructions. All Alinity-positive samples were subsequently tested using the clinically validated Allplex HPV HR Detection Assay (Seegene Inc., Seoul, South Korea) according to manufacturer instructions. We assessed the overall, age-stratified prevalence of cervical infections with 14 HPV types detectable by the Alinity assay (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) (hereby 14-Alinity targeted HPV types) and the type-specific, age stratified prevalence of cervical infections with 12 high-risk HPV types (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) classified as Group 1 “carcinogenic to humans” by the International Agency for Research on Cancer (IARC) (hereby 12-IARC defined hrHPV types), excluding HPV66 and HPV68. We additionally assessed cervical HPV prevalence among women, aged 20–24 at the time of study inclusion, who were eligible for HPV vaccination during adolescence, stratifying the analysis by vaccination status. Data collected in 2023–2025, following the implementation of the school-based HPV vaccination programme, were compared with those from a methodologically comparable cross-sectional study conducted in 2009–2010, prior to the school-based HPV vaccination programme. Both studies enrolled Slovenian women aged 20–64 years attending the NCCSP, applied the same inclusion and exclusion criteria and used the same clinically validated HPV assay, allowing for a direct comparison. HPV prevalence was estimated with 95% confidence intervals (CI) using the Wilson method for proportions. Differences in prevalence were assessed using Pearson’s chi-square test or Fisher’s exact test for small sample sizes. Statistical significance was defined as a two-sided p-value < 0.05. All analyses were performed using IBM SPSS Statistics version 30 (IBM Corp., Armonk, NY, USA) and R version 4.5.1 (Free Software Foundation, Boston, MA, USA). Results A total of 4,419 women were included in the final dataset for analysis. In 2023–2025, the overall prevalence of cervical infections with 14-Alinity targeted HPV types among Slovenian women aged 20–64 years was 10.0% (95% CI: 9.2%–10.9%), significantly lower than the 13.3% prevalence observed in 2009–2010 (95% CI: 12.3%–14.3%
Author: Lasič, Mateja
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7160971299