Anneli Uuskula

Understanding the high-risk human papillomavirus prevalence and associated factors in the European country with a high incidence of cervical cancer

Abstract Background High-risk human papillomavirus (HR-HPV) is a known cause of cervical cancer (CC). Latvia has a high incidence of CC compared with the average incidence in the European Union. This study aims to fill the data gap on the HR-HPV burden in Latvia, providing information on its prevalence and associated factors. Methods The cross-sectional study was conducted from February 2021 to April 2022. Participants 25–70 years old visiting a general practitioner (general population) or those referred to a colposcopy clinic with changes in their cervical cytology (colposcopy population) collected vaginal self-sample and completed a paper-based questionnaire. Samples were analyzed with Cobas 6800 System (Roche) for HPV16, HPV18 and other HR-HPV (HPV31/33/35/39/45/51/52/56/58/59/66/68). Descriptive statistics for categorical variables were performed. The Chi-square test was used to determine for the statistical significance of differences in the proportions of the dependent variable between subgroups of the independent variable. Univariate and multivariate binary logistic regression were used to identify factors associated with positive HR-HPV status. Results were considered statistically significant at P < 0.05. Results A total of 1274 participants provided a valid sample. The prevalence of any HR-HPV infection was 66.8% in the colposcopy group and 11.0% in the general population. Factors associated with positive HR-HPV status were marital status single/divorced/widowed (vs. married/cohabiting) [adjusted OR (aOR) 2.6; P = 0.003], higher number of lifetime sex partners [aOR 5.1 (P < 0.001) and 4.0 (P = 0.001)] for six or more and three to five partners in the general population; in the colposcopy group, the statistical significance remained only for Latvian ethnicity (vs. other) (aOR 1.8; P = 0.008) and current smoking (vs. never) (aOR 1.9; P = 0.01). Conclusion We documented a comparison to European Union HR-HPV infection burden in Latvia. Any HR-HPV positivity was significantly associated with sexual and other health behavior.

Cross-population evaluation of cervical cancer risk prediction algorithms

Cervical cancer is a preventable disease, despite being one of the most common types of female cancers worldwide. Integrating existing programs for cervical cancer screening with personalized risk prediction algorithms can improve population-level cancer prevention by enabling more targeted screening and contrive preventive healthcare innovations. While algorithms developed for cervical cancer risk prediction have shown promising performance in internal validation on more homogeneous populations, their ability to generalize to external populations remains to be assessed. To address this gap, we perform a cross-population comparative study of personalized prediction algorithms for more personalized cervical cancer screening. Using data from the Norwegian and Estonian populations, the algorithms are validated on internal and external datasets to study their potential biases and limitations when applied to different populations. We evaluate the algorithms in predicting progression from low-grade precancerous cervical lesions, simulating a clinically relevant application of more personalized risk stratification. As expected, our numerical experiments show that algorithm performance varies depending on the population. However, some algorithms show strong generalization capacity across different data sources. Using Kaplan-Meier estimates, we demonstrate the strengths and limitations of the algorithms in detecting cancer progression over time by comparing to the trends observed from data. We assess their overall discrimination performance in personalized risk predictions by analyzing the accuracy and confidence in individual risk estimates. This study examines the effectiveness of personalized prediction algorithms across different populations. Our results demonstrate the potential for generalizing risk prediction algorithms to external populations. These findings highlight the importance of considering population diversity when developing risk prediction algorithms.

Age-specific and genotype-specific carcinogenic human papillomavirus prevalence in a country with a high cervical cancer burden: results of a cross-sectional study in Estonia

Objectives To describe age-specific and type-specific carcinogenic human papillomavirus (HPV) prevalence prior to large-scale effect of HPV vaccines in Estonia and to analyse the risk factors associated with carcinogenic HPV. Design Cross-sectional study using self-administered questionnaire and self-collected vaginal swabs for detection of HPV infection. Setting Estonian Biobank database. Participants Stratified random sample of women aged 30–33, 57–60 and 67–70 years living in one of the three largest counties in Estonia. Of 3065 women approached, 1347 (43.9%) returned questionnaires and specimens for HPV DNA detection. Outcome measures HPV prevalence and fully adjusted ORs with 95% CIs for risk factors. Results HPV prevalence was highest among women aged 30–33 years (18.7%; 95% CI 15.8 to 21.9) followed by those aged 67–70 years (16.7%; 95% CI 12.4 to 22.0) and 57–60 years (10.2%; 95% CI 7.8 to 13.3). HPV16 and HPV56 were the most common among women aged 30–33 years (both 4.0%; 95% CI 2.7 to 5.9), and HPV68 was the most common among women aged 57–60 years (2.8%; 95% CI 1.5 to 4.7) and 67–70 years (6.4%; 95% CI 3.6 to 10.4). Vaccination with nonavalent vaccine would have halved the carcinogenic HPV prevalence among women aged 30–33 years. The odds of infection with carcinogenic HPV were higher among women with six or more sexual partners among younger (OR 2.99; 95% CI 1.54 to 5.81) and older (OR 3.80; 95% CI 1.25 to 11.55) women and lower (OR 0.35; 95% CI 0.17 to 0.72) among younger married women. Conclusions This study demonstrated U-shaped age-specific genotype profile of carcinogenic HPV prevalence, indicating that public health providers should focus on developing exit strategies for the cervical cancer screening programme in Estonia with a possible extension of HPV testing beyond the current screening age of 65 years. Generalisability of the findings of this study may be affected by the low response rate.

How can cervical screening meet the needs of vulnerable women? A qualitative comparative study with stakeholder perspectives from seven European countries

Objective This study explored and compared stakeholder perspectives on enhancements to cervical cancer screening for vulnerable women across seven European countries. Design In a series of Collaborative User Boards, stakeholders were invited to collaborate on identifying facilitators to improve cervical cancer screening. Setting This study was part of the CBIG-SCREEN project which is funded by the European Union and targets disparities in cervical cancer screening for vulnerable women ( www.cbig-screen.eu ). Data collection took place in Bulgaria, Denmark, Estonia, France, Italy, Portugal and Romania. Participants Represented stakeholders at various levels, including user representatives (vulnerable women), healthcare professionals, social workers, programme managers and decision makers. Methods 14 meetings lasting 2 hours each were held in these seven countries between October 2021 and June 2022. The meetings were audio or video recorded, transcribed and translated into English for qualitative framework analysis. Results We engaged 120 participants in the Collaborative User Boards. Proposed solutions targeted both provider and system levels. In all countries, fostering trusting relationships between vulnerable women and social or healthcare professionals, coupled with community outreach for awareness and access to testing was a consistent recommendation. Participants in Estonia, Denmark, France, Italy, Portugal and Romania advocated for tailoring healthcare services to meet the unique needs of vulnerable populations through a holistic approach. In Bulgaria and Romania, participants advocated for the need to secure free access, from screening to follow-up, and emphasised the need for organised screening with target population screening registries. Conclusion The study offers insights into stakeholders' recommendations for enhancing cervical cancer screening services for vulnerable women across seven European countries. Despite variations in the implementation level of population-based screening programmes, the imperative to optimise outreach and proximity work to improve cervical cancer screening resonated across all countries.

What are the barriers towards cervical cancer screening for vulnerable women? A qualitative comparative analysis of stakeholder perspectives in seven European countries

Objectives The aim of this study was to map and compare stakeholders’ perceptions of barriers towards cervical cancer screening for vulnerable women in seven European countries. Design In Collaborative User Boards, stakeholders were invited to participate to identify barriers towards participation in cervical cancer screening. Setting The study is nested in the European Union-funded project CBIG-SCREEN which aims to tackle inequity in cervical cancer screening for vulnerable women ( www.cbig-screen.eu ). Data collection took place in Bulgaria, Denmark, Estonia, France, Italy, Portugal and Romania. Participants Participants represented micro-level stakeholders covering representatives of users, that is, vulnerable women, meso-level stakeholders covering healthcare professionals and social workers, and macro-level stakeholders covering programme managers and decision-makers. Methods Across the seven countries, 25 meetings in Collaborative User Boards with a duration of 2 hours took place between October 2021 and June 2022. The meetings were video recorded or audio recorded, transcribed and translated into English for a qualitative framework analysis. Results 120 participants took part in the Collaborative User Boards. Context-specific barriers were related to different healthcare systems and characteristics of vulnerable populations. In Romania and Bulgaria, the lack of a continuous screening effort and lack of ways to identify eligible women were identified as barriers for all women rather than being specific for women in vulnerable situations. The participants in Denmark, Estonia, France, Italy and Portugal identified providers’ lack of cultural and social sensitivity towards vulnerable women as barriers. In all countries, vulnerable women’s fear, shame and lack of priority to preventive healthcare were identified as psychological barriers. Conclusion The study provides an overview of stakeholders’ perceived barriers towards vulnerable women’s cervical cancer screening participation in seven European countries. The organisation of healthcare systems and the maturity of screening programmes differ between countries, while vulnerable women’s psychological barriers had several similarities.