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

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.

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.

Expanding eligibility and improving quality of cervical cancer screening in Estonia: The 2021 reforms.

Estonia has one of the highest death rates from cervical cancer in the European Union despite having had a population-based screening programme for over 15 years. In 2021, this high disease burden, alongside a new national cancer prevention plan, prompted a series of cervical cancer screening programme reforms to address low screening uptake and evidence of variable screening test quality. The reforms had three main elements: expansion of eligibility to all women aged 30-65 regardless of insurance status; increasing test provision by enabling family physicians to take screening samples and introducing self-sampling; and improving testing procedures, replacing cytology with HPV testing as the primary screening test. Although the impact of these changes is yet to be seen, early signs suggest increased programme participation. However, at 51 %, further action to address barriers to uptake will likely be necessary. If Estonia is to avoid another period of policy dormancy, as happened between 2006 and 2021, greater clarity on screening programme accountability is required. The establishment of the National Cancer Screening Group may enable this. The first test will be the delivery of an end-to-end evaluation of the reformed programme, with an emphasis on equity of access. The next step will be to develop and deliver solutions that respond to these needs.

Polygenic risk scores for cervical HPV infection, neoplasia and cancer show potential for personalised screening: comparison of two methods.

The era of precision medicine requires the achievement of accurate risk assessment. Polygenic risk scores (PRSs) have strong potential for increasing the benefits of nationwide cancer screening programs. The current pool of evidence on the role of a PRS as a risk stratification model in actual practice and implementation is limited. To better understand the impact of possible method-induced variance, we constructed and validated two PRSs for cervical cancer (CC) using the Estonian Biobank female population (691 CC cases and 13,820 controls) and evaluated their utility in predicting incident cervical neoplasia (CIN), cancer, and human papillomavirus (HPV) infection using two methods (LDPred and BayesRR-RC). This study demonstrated that two genetic risk scores were significantly associated with CIN, CC, and HPV infection incidence. Independent of the method, we demonstrated that women with elevated PRS values reached the observed cumulative risk levels of CIN or CC much earlier. Our results indicated that the PRS-based discrimination rules could differ substantially when the PRSs contain similar predictive information. In summary, our analysis indicated that PRSs represent a personalized genetic component that could be an additional tool for cervical cancer risk stratification, and earlier detection of abnormalities provides invaluable information for those at high risk.

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.

An overview of cervical cancer epidemiology and prevention in the Baltic States.

AIMS: To inform future Baltic States-specific policy analyses, we aimed to provide an overview of cervical cancer epidemiology and existing prevention efforts in Estonia, Latvia and Lithuania. METHODS: A structured desk review: we compiled and summarized data on current prevention strategies, population demography and epidemiology (high risk human papillomavirus (HPV) prevalence and cervical cancer incidence and mortality over time) for each Baltic State by reviewing published literature and official guidelines, performing registry-based analyses using secondary data and having discussions with experts in each country. RESULTS: We observed important similarities in the three Baltic States: high burden of the disease (high incidence and mortality of cervical cancer, changes in TNM (Classification of Malignant Tumors) stage distribution towards later stage at diagnosis), high burden of high-risk HPV in general population and suboptimal implementation of the preventive strategies as low screening and HPV vaccination coverage. CONCLUSIONS: Cervical cancer remains a substantial health problem in the region and the efforts in addressing barriers by implementing a four-step plan for elimination cervical cancer in Europe should be made. This goal is achievable through evidence-based steps in four key areas: vaccination, screening, treatment, and public awareness.

Prevaccination Prevalence of Type-Specific Human Papillomavirus Infection by Grade of Cervical Cytology in Estonia.

Importance: Large-scale data on type-specific human papillomavirus (HPV) prevalence and disease burden worldwide are needed to guide cervical cancer prevention efforts. Promoting the research and application of health care big data has become a key factor in modern medical research. Objective: To examine the prevaccination prevalence of high-risk HPV (hrHPV) and type distribution by cervical cytology grade in Estonia. Design, Setting, and Participants: This cross-sectional study used text mining and the linking of data from electronic health records and health care claims to examine type-specific hrHPV positivity in Estonia from 2012 to 2019. Participants were women aged at least 18 years. Statistical analysis was performed from September 2021 to August 2022. Main Outcomes and Measures: Type-specific hrHPV positivity rate by cervical cytological grade. Results: A total of 11 017 cases of cervical cytology complemented with data on hrHPV testing results between 2012 and 2019 from 66 451 women aged at least 18 years (mean [SD] age, 48.1 [21.0] years) were included. The most common hrHPV types were HPV16, 18, 31, 33, 51 and 52, which accounted for 73.8% of all hrHPV types detected. There was a marked decline in the positivity rate of hrHPV infection with increasing age, but the proportion did not vary significantly based on HPV type. Implementation of nonavalent prophylactic vaccination was estimated to reduce the number of women with high-grade cytology by 50.5% (95% CI, 47.4%-53.6%) and the number with low-grade cytology by 27.8% (95% CI, 26.3%-29.3%), giving an overall estimated reduction of 33.1% (95% CI, 31.7%-34.5%) in the number of women with precancerous cervical cytology findings. Conclusions and Relevance: In this cross-sectional study, text mining and natural language processing techniques allowed the detection of precursors to cervical cancer based on data stored by the nationwide health system. These findings contribute to the literature on type-specific HPV distribution by cervical cytology grade and document that α-9 phylogenetic group HPV types 16, 31, 33, 52 and α-7 phylogenetic group HPV 18 are the most frequently detected in normal-to-high-grade precancerous lesions in Estonia.

Cervical Cancer in the Baltic States: Can Intelligent and Personalized Cancer Screening Change the Situation?

The three Baltic States (Estonia, Latvia, and Lithuania) are among the European Union countries with the highest incidence and mortality rates for cervical cancer. In order to tackle this public health challenge, there is an urgent need to implement more advanced and effective methods in cervical cancer prevention in Baltic countries. Nationwide cervical cancer screening programs in the Baltic States commenced in 2004-2009. While the organized screening programs in these countries differ in some relevant details (target age groups, screening interval), the underlying principles and problems, barriers are universal. However, the outcomes of present screening programs are unsatisfactory. In addition, universal screening programs are extremely costly. There is a potential need for more intelligent and personalized cervical cancer screening program. In 2019 the project "Towards elimination of cervical cancer: intelligent and personalized solutions for cancer screening" (2020-2023) was developed with the main objective - to develop improved and personalized cancer screening methods within a sustainable health care system. It is expected, that more sophisticated cervical cancer screening model will be implemented in Estonia, Latvia, and Lithuania, and will have a positive impact to epidemiology of cervical cancer and public health in general.

Long-term mortality following SARS-CoV-2 infection: A national cohort study from Estonia.

Background: The objective of this study was to describe 12-month mortality following SARS-CoV-2 infection compared with a reference population with no history of SARS-CoV-2. Methods: Nationwide cohort study using electronic health care data on SARS-CoV-2 RNA positive cases (n= 66,287) and reference group subjects (n=254,969) with linkage to SARS-CoV-2 testing and death records. Findings: People infected with SARS-COV-2 had more than three times the risk of dying over the following year compared with those who remained uninfected (aHR 3·1, 95%CI 2·9-3·3). Short-term mortality (up to 5 weeks post-infection) was significantly higher among COVID-19 group (1623·0/10 000) than in the reference group (118/10 000). For COVID-19 cases aged 60 years or older, increased mortality persisted until the end of the first year after infection, and was related to increased risk for cardiovascular (aHR 2·1, 95%CI 1·8-2·3), cancer (aHR 1·5, 95%CI 1·2-1·9), respiratory system diseases (aHR 1·9, 95%CI 1·2-3·0), and other causes of death (aHR 1·8, 95%CI 1·4-2·2). Interpretation: Increased risk of death from SARS-CoV-2 is not limited to the acute illness: SARS-CoV-2 infection carries a substantially increased mortality in the following 12 months. This excess death mainly occurs in older people and is driven by broad array of causes of death. Funding: Research was carried out with the support of Estonian Research Council (grants PRG1197, PRG198), European Regional Development Fund (RITA 1/02-120) and European Social Fund via IT Academy program.

Cervical cancer screening patterns among HIV-positive women in Estonia: a population-based retrospective cohort study.

BACKGROUND: The World Health Organisation (WHO) calls for the elimination of cervical cancer (CC) as a public health issue. To achieve elimination, efforts must be aligned and accelerated. Women living with HIV (WLWH) have excess risk for developing, and dying from, CC over the general population. Estimates of cervical cancer screening programme coverage in Eastern European countries that have experienced HIV epidemics since the early 2000's are scarce. METHOD: This population-based retrospective study uses a healthcare administrative database and follows cohorts of all WLWH in a ratio of 1:3 randomly matched (age, region) HIV negative women from 2009 to 2018. Annual and longitudinal (over the whole study period) coverage for cervical cancer screening (opportunistic, organised, HIV specific) and adjusted odds ratios (AORs) for longitudinal screening coverage predictors were estimated from 2009 to 2018. RESULTS: Among WLWH and HIV-negative women, the mean annual coverage with opportunistic screening was 61.45 and 65.59%; and organised screening was 20.4 and 28.7%, respectively (both: p < 0.00001). 19.01% (95% CI 18.05-19.97) HIV-negative and 13.9% (95% CI 12.35-15.45) WLWH were longitudinally covered with organised cervical cancer screening. Among WLWH, the mean annual HIV-specific cervical cancer screening coverage was 49.4, and 24.3% were longitudinally covered. Longitudinal coverage with HIV-specific cervical cancer screening was inversely associated with age, hepatitis C virus (HCV) co-infection (AOR 0.754, 95% CI 0.619, 0.916), not having insurance (AOR 0.331, 95% CI 0.264, 0.412), drug abuse (AOR 0.459, 95% CI 0.336, 0.618) and higher among those retained in HIV care (AOR 1.972, 95% CI 1.615, 2.410). Among HIV-negative women, longitudinal coverage with organised cervical cancer screening was inversely associated with residence in the region and higher among older women. CONCLUSIONS: Our results highlight unacceptably low coverage of cervical cancer screening of WLWH in Estonia. There is need for dedicated cervical cancer screening efforts for WLWH considering the high cancer risk and rate in the study population.

The mortality and psychological burden caused by response to COVID-19 outbreak.

The world is experiencing a severe COVID-19 outbreak. To control this outbreak, many governments in the world have imposed lockdown or quarantine measures. We hypothesize that these measures may cause additional mortality and morbidity in the (near) future due to delay in diagnosing diseases and other indirect effect on health (such as economic crisis). To support this hypothesis and to estimate the additional mortality that may linked to the COVID-19 controlling policy, we performed a step-by-step pragmatical approach. First, we chose a country (The Netherlands), and looked at the most common causes of mortality in this country. Then, we performed a literature study on the additional mortality when these causes were diagnosed late, and selected a paper with the most severe scenario. We also performed a literature study on the effect of economic crisis on additional mortality. The mortality data were then extrapolated to the demography of The Netherlands, and the results were compared with the present data on deaths directly due to COVID-19. Roughly, we forecast 388 additional deaths a week in The Netherlands in 5 years due to the direct and indirect effects of the lockdown measures. The most important implications of this hypothesis is that the additional mortality and increased mental health problem should be considered in evaluating the necessity of lock down and quarantine policy.