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.

Cervical microbiota dysbiosis associated with high-risk Human Papillomavirus infection.

High-risk Human Papillomavirus (HR-HPV) genotypes, specifically HPV16 and HPV18, pose a significant risk for the development of cervical intraepithelial neoplasia and cervical cancer. In the multifaceted cervical microenvironment, consisting of immune cells and diverse microbiota, Lactobacillus emerges as a pivotal factor, wielding significant influence in both stabilizing and disrupting the microbiome of the reproductive tract. To analyze the distinction between the cervical microbiota and Lactobacillus-dominant/non-dominant status of HR-HPV and non-infected healthy women, sixty-nine cervical swab samples were analyzed, included 44 with HR-HPV infection and healthy controls. All samples were recruited from Human Papillomavirus-based cervical cancer screening program and subjected to 16s rRNA sequencing analysis. Alpha and beta diversity analyses reveal no significant differences in the cervical microbiota of HR-HPV-infected women, including 16 and 18 HPV genotypes, and those with squamous intraepithelial lesion (SIL), compared to a control group. In this study we identified significantly lower abundance of Lactobacillus mucosae in women with HR-HPV infection compared to the control group. Furthermore, changes in bacterial diversity were noted in Lactobacillus non-dominant (LND) samples compared to Lactobacillus-dominant (LD) in both HR-HPV-infected and control groups. LND samples in HR-HPV-infected women exhibited a cervical dysbiotic state, characterized by Lactobacillus deficiency. In turn, the LD HR-HPV group showed an overrepresentation of Lactobacillus helveticus. In summary, our study highlighted the distinctive roles of L. mucosae and L. helveticus in HR-HPV infections, signaling a need for further research to demonstrate potential clinical implications of cervical microbiota dysbiosis.

Left and right ventricular systolic function impairment in type 1 diabetic young adults assessed by 2D speckle tracking echocardiography.

AIMS: Subclinical left ventricular (LV) and right ventricular (RV) systolic dysfunction has been proved in type 2 diabetes mellitus (DM). There is lack of uniform data on systolic myocardial function in type 1 DM. The aim of this study was to evaluate LV and RV function with 2D speckle tracking echocardiography (2D STE) in adult type 1 diabetic patients. METHODS AND RESULTS: Totally, 50 patients with type 1 DM and 50 control subjects in the same range of age were prospectively evaluated. The 2D STE assessment of LV longitudinal, radial, circumferential strain and RV free-wall longitudinal strain was performed. In diabetic group, left ventricular global longitudinal strain (LVGLS), left ventricular global circumferential strain (LVGCS), left ventricular radial strain at basal level (LVRS-basal), and right ventricular free-wall global longitudinal strain (RVGLS) were significantly lower compared with the controls: LVGLS (-20.3 ± 2.0% vs. -22.2 ± 1.8%, P < 0.001), LVGCS (-21.1 ± 2.5% vs. -22.2 ± 2.4%, P < 0.05), LVRS-basal (50.5% ± 11.5 vs. 57.1% ±17.0, P < 0.05), and RVGLS (-30.1% ± 3.5 vs. -32.7% ± 3.9, P < 0.01). Multivariable logistic regression analysis showed that the only independent predictor of reduced LVGLS was low-density lipoprotein cholesterol [odds ratio 3.65 (95% confidence interval: 1.27-10.5), P = 0.014]. CONCLUSION: Type 1 DM is associated with subclinical LV systolic dysfunction and worse RV systolic function, which can be detected with 2D STE.

Left Atrial Enlargement in Young High-Level Endurance Athletes - Another Sign of Athlete's Heart?

Enlargement of the left atrium is perceived as a part of athlete's heart syndrome, despite the lack of evidence. So far, left atrial size has not been assessed in the context of exercise capacity. The hypothesis of the present study was that LA enlargement in athletes was physiological and fitness-related condition. In addition, we tried to assess the feasibility and normal values of left atrial strain parameters and their relationship with other signs of athlete's heart. The study group consisted of 114 international-level rowers (17.5 ± 1.5 years old; 46.5% women). All participants underwent a cardio-pulmonary exercise test and resting transthoracic echocardiography. Beside standard echocardiographic measurements, two dimensional speckle tracking echocardiography was used to assess average peak atrial longitudinal strain, peak atrial contraction strain and early left atrial diastolic longitudinal strain. Mild, moderate and severe left atrial enlargement was present in 27.2°%, 11.4% and 4.4% athletes, respectively. There were no significant differences between subgroups with different range of left atrial enlargement in any of echocardiographic parameters of the left ventricle diastolic function, filling pressure or hypertrophy. A significant correlation was found between the left atrial volume index and maximal aerobic capacity (R > 0.3; p < 0.001). Left atrial strain parameters were independent of atrial size, left ventricle hypertrophy and left ventricle filling pressure. Decreased peak atrial longitudinal strain was observed in 4 individuals (3.5%). We concluded that LA enlargement was common in healthy, young athletes participating in endurance sport disciplines with a high level of static exertion and was strictly correlated with exercise capacity, therefore, could be perceived as another sign of athlete's heart.