Self-reported participation in cervical cancer screening among Polish women in 2004-2019.

OBJECTIVES: We aimed to assess self-reported participation in cervical cancer screening among Polish women between 2004 and 2019 and to identify the groups with the lowest participation rate. MATERIAL AND METHODS: Data on declared participation in cervical cancer screening were obtained from the European Health Interview Survey from 2004 to 2019. RESULTS: In 2019, 86.7% of Polish women aged ≥ 15 years declared that they had ever undergone a Pap test. Compared to 2004, the coverage of ever-screened women improved by 16.6 percentage points. The proxy population coverage was 72.9%. The highest proportion of women who underwent a Pap smear in the last three years was observed among those aged 35-44 years and 25-34 years (84.0% and 83.2%, respectively), and the lowest among women aged ≥ 75 years (20.5%). The proportion screened within the last three years also varied by education (up to lower secondary education 26.4%, up to post-secondary non-tertiary education 62.8%, and the highest level of education 83.7%), urbanization (large cities 66.7%, suburbs, and smaller cities 62.8%, and rural areas 59.0%), income (poorest households 42.5%, wealthiest households 70.6%), and declared health status (best 68.9%, worst 41.4%). The lowest participation in screening was observed in the southeastern regions and the highest in the northwestern regions of Poland. CONCLUSIONS: In Poland, in 2019, the approximate coverage of cervical cancer screening was high compared to other European countries and has improved over the last 15 years. A complete screening registry is required to confirm questionnaire-based self-reported data. Targeted interventions should be implemented to address low participation in the identified regions and socioeconomic groups.

HPV testing in Polish population-based cervical cancer screening programme (HIPPO project)-study protocol of a randomised healthcare policy trial.

BACKGROUND: An Organised Cervical Cancer Screening Programme (OCCSP) was started in Poland in 2006/2007. Each woman aged 25 to 59 is eligible for a free Pap test every 3 years in OCCSP. Despite implementation of the OCCSP, the age-standardised cervical cancer (CC) incidence and mortality rates in 2019 were 7.3/100 000 and 3.9/100 000 respectively and were still higher than those in Western European countries with well-organised screening programmes. Apart from low coverage of the OCCSP, suboptimal performance of the screening test (conventional cytology) may be partially responsible for this situation. Several countries have already incorporated high risk Human Papillomavirus (hrHPV) testing in CC screening as a more sensitive tool reducing the risk of missing precancerous lesions and allowing for extension of screening intervals. The European Guidelines for Quality Assurance in Cervical Cancer Screening recommend pilot evaluation of a new screening test in country-specific conditions before its implementation. METHODS: The HIPPO project (HPV testing In Polish POpulation-based cervical cancer screening program) is a randomised health services study nested in the OCCSP in Poland. The project will randomise 33 000 women aged 30-59 years to cytology or hrHPV testing (ratio: 1:1) with age stratification. In the cytology arm women with repeated Atypical Squamous Cells of Undetermined Significance (ASC-US) or ≥ Low-Grade Squamous Intraepithelial Lesions (LSIL) are referred for colposcopy. In the other arm, hrHPV ( +) women with ≥ ASC-US reflex Liquid-Based Cytology (LBC) are referred for colposcopy. Primary endpoints include detection rates of histologically confirmed high grade intraepithelial lesions or worse (CIN2 +) in each arm. DISCUSSION: This pilot randomised healthcare study nested in the OCCSP in Poland will assess and compare the performance of hrHPV testing to current standard-cytology in order to make decisions on implementation of HPV-based screening in the country. TRIAL REGISTRATION: This randomised healthcare service study was prospectively registered at https://clinicaltrials.gov/ (identifier: NCT04111835, protocol ID 28/2019) on 19th of September 2019.

Simple yet (more?) effective. Venous thromboembolism risk assessment model for germ cell tumour patients receiving first-line chemotherapy.

BACKGROUND: Germ cell tumours (GCT) are highly curable malignancies. Venous thromboembolism (VTE) is a serious complication, needing better risk assessment models (RAM). AIM: Identification of VTE incidence and risk factors in metastatic GCT patients starting first-line chemotherapy. Developing a RAM and comparing it to Khorana risk score (KRS) and Padua Prediction Score (PPS). MATERIAL AND METHODS: We retrospectively analysed GCT patients staged IS-IIIC. VTE risk factors were identified with logistic regression. Area under curve of receiver operating characteristic (AUC-ROC), Akaike and Bayesian Information Criteria (AIC, BIC) were calculated for the developed RAM, KRS and PPS. RESULTS: Among 495 eligible patients, VTE occurred in 69 (13.9%), including 40 prior to chemotherapy. Vein compression (OR: 8.96; 95% CI: 2.85-28.13; p < 0.001), clinical stage IIIB-IIIC (OR: 5.68; 95% CI: 1.82-17.70; p = 0.003) and haemoglobin concentration (OR for 1 g/dL decrease: 1.32; 95% CI: 1.03-1.67; p = 0.026) were significant in our RAM. KRS ≥ 3 (OR: 3.31; 95% CI: 1.77-6.20; p < 0.001), PPS 4-5 (OR: 3.06; 95% CI: 1.49-6.29; p = 0.002) and PPS > 5 (OR 8.05; 95% CI 3.79-17.13; p < 0.001) correlated with VTE risk. Diagnostic criteria (AUC-ROC, AIC, BIC) for the developed RAM, KRS and PPS were (0.885; 0.567; -1641), (0.588; 0.839; -1576) and (0.700; 0.799; -1585), respectively. In the numerical score, the optimal cut-off point for high-risk was ≥9, with sensitivity, specificity, positive and negative predictive value of 0.78, 0.77, 0.35 and 0.96, respectively. CONCLUSIONS: Our RAM, based on vein compression, clinical stage and haemoglobin concentration proved superior to both KRS and PPS. VTE is frequent in GCT patients.

Reasons for truly negative cytology reports preceding the diagnoses of invasive cervical cancer-Results of a false-negative cytology audit in Polish Cervical Cancer Screening Programme.

BACKGROUND: False-negative (FN) results in cervical cancer (CC) screening pose significant risk for participants and should be audited. The aim of the study was to analyse the results of audit of FN slides collected in 2010-2013 in Polish Cervical Cancer Screening Program (CCSP) and to seek for risk factors of obtaining true-negative result (TN; not containing abnormal cells as confirmed in audit) before CC diagnosis. METHODS: Screening database was merged with National Cancer Registry to identify negative slides preceding histologically confirmed CC diagnosis up to 42 months. Two blinding slides were randomly assigned per each FN. The whole set was reassessed independently by three pathologists with 30 years of experience in cytology evaluation. Final audit result was established in the case of ≥2 coherent reports. Agreement rates and kappa (κ) coefficients were calculated. Logistic analysis of risk factors for obtaining TN result was performed. RESULTS: Of 374 included FNs, 204 were considered abnormal (54.6%) and 91 were confirmed negative for intraepithelial neoplasia (24.3%). Agreement between experts was moderate for FNs (κ = 0.266) and fair for blinding slides (κ = 0.142) when grouping abnormal slides. Adenocarcinoma diagnosis elevated the risk of TN result (OR = 3.83); detection of macroscopic changes on the cervix and smoking lowered the risk (OR = 0.39, OR = 0.40 respectively). CONCLUSIONS: Misinterpretation was the main reason for FN cytology in the CCSP which indicated the need of further personnel training to increase screening quality. Rather low agreement between auditors requires further insight. A standardised process of auditors' selection should be planned to increase audit quality.

False Negative Results in Cervical Cancer Screening-Risks, Reasons and Implications for Clinical Practice and Public Health.

False negative (FN) results in cervical cancer (CC) screening pose serious risks to women. We present a comprehensive literature review on the risks and reasons of obtaining the FN results of primary CC screening tests and triage methods and discuss their clinical and public health impact and implications. Misinterpretation or true lack of abnormalities on a slide are the reasons of FN results in cytology and p16/Ki-67 dual-staining. For high-risk human papillomavirus (HPV) molecular tests, those include: truly non-HPV-associated tumors, lesions driven by low-risk HPV types, and clearance of HPV genetic material before sampling. Imprecise disease threshold definition lead to FN results in visual inspection with acetic acid. Lesions with a discrete colposcopic appearance are a source of FN in colposcopic procedures. For FAM19A4 and hsa-miR124-2 genes methylation, those may originate from borderline methylation levels. Histological misinterpretation, sampling, and laboratory errors also play a role in all types of CC screening, as well as reproducibility issue, especially in methods based on human-eye evaluation. Primary HPV-based screening combined with high quality-assured immunocytochemical and molecular triage methods seem to be an optimal approach. Colposcopy with histological evaluation remains the gold standard for diagnosis but requires quality protocols and assurance measures.

Interlaboratory agreement in assessment of gynaecological cytology in Cervical Cancer Screening Programme in Poland - a pilot evaluation.

In our pilot study we have aimed to assess interlaboratory variability of cytological diagnoses in selected laboratories participating in the Polish Cervical Cancer Screening Programme (CCSP) to establish grounds for certification system for cytodiagnosticians and to monitor the quality of services. Set of 50 selected Pap smears, previously reassessed by an expert on the grounds of clinical, colposcopic and histological data was blinded and sent to 15 laboratories in Poland with request for evaluation according to routine practice according to the Bethesda 2001 system. Concordance with expert diagnoses reached a median of 82% (range: 66% to 92%), with median unweighted κ coefficient at κ = 0.67 (range 0.40 to 0.86) depending on laboratory. This indicates substantial agreement among laboratories, however with essential differences in proper evaluation in some outlying laboratories. Agreement was highest in samples with high-grade, lower for low-grade abnormalities. Slides with ASC-US and ASC-H expert diagnoses were most troubling for cytodiagnosticians. Sets of highly selected cytological slides with expert diagnoses may serve as a tool in the process of comprehensive periodic recertification of cytodiagnosticians in the screening programme. A benchmark level of agreement with expert diagnoses should be established to guide corrective actions for cytodiagnosticians with lowest agreement.

Risk factors of cervical cancer after a negative cytological diagnosis in Polish cervical cancer screening programme.

Risk factors of cervical cancer (CC) development are well investigated, however, those influencing the risk of a potential false negative cytology preceding diagnosis of an invasive CC are not. We have aimed to explore these factors according to the data from Organised Cervical Cancer Screening Programme (OCCSP) in Poland. A total of 2.36 million of Pap tests sampled in 2010-2012 within OCCSP were merged with the Polish National Cancer Registry to identify CC cases after abnormal cytology and after normal cytology within 3 years of screening. Of 1460 invasive CCs, 1025 were preceded by abnormal and 399 by normal cytology result. Multivariate logistic analysis indicated that the presence of microorganisms in the Pap (OR = 2.18, 95% CI 1.65-2.87), evaluation by smaller (below 9000 slides processed per year) laboratories (OR = 1.60, 95% CI 1.22-2.09) and non-squamous histology of cancer increased the odds for a potential false negative result (OR = 3.39, 95% CI 2.37-4.85 for adenocarcinoma, OR = 1.99, 95% CI 1.11-3.55 for other types of carcinoma), whereas cervical ectropion, other macroscopic changes on the cervix and smoking decrease the odds for a potential false negative Pap test result preceding CC (OR = 0.61, 95% CI 0.45-0.82, OR = 0.41, 95% CI 0.25-0.67, OR = 0.60, 95% CI 0.46-0.78, respectively). Proper triage of women with microscopic signs of microorganisms in the Pap smear should be reconsidered and cytology should be assessed in laboratories processing over 9000 slides annually to decrease the odds for negative Pap test result in 2 years before CC diagnosis. Information on macroscopic changes on the cervix provided to cytomorphologist may reduce the risk of a potential false negative cytology result.

Why are Polish women diagnosed with invasive cervical cancer after negative cytology in the organized screening programme - a pilot reevaluation of negative Pap smears preceding diagnoses of interval cancers.

We have aimed to study reasons for reporting false-negative cytology results preceding diagnosis of interval cervical cancers (CC) in Poland. Data on all Pap smears collected in the organised screening in 2010-2015 were retrieved from the electronic database and linked with Polish National Cancer Registry (PNCR) data. False-negative results were defined as those sampled and assessed normal up to 3.5 years before diagnosis of invasive CC. False-negative slides were then seeded among twice as many randomly selected slides from the same lab and reviewed independently by three expert cytomorphologists. New diagnosis was established when experts agreed on a result. Of 48 selected false-negative slides, 1 case was diagnosed as a low-grade abnormality, 22 cases as a high-grade abnormalities, 3 cases as unsatisfactory for evaluation and 5 as no intraepithelial lesion of malignancy (NILM) by all three experts. There was no agreement in 17 cases. Percentages of agreement between experts was 64.6. Interobserver agreement rate was moderate with Fleiss' κ values. Our pilot study indicates evaluation errors as the main reason of false-negative cytology preceding interval CC in the organized screening programme in Poland. True lack of abnormal cells on the slide is the next reason.