Beata Smolarz

Abstract Endometriosis is a common complex inflammatory condition characterised by the presence of endometrium-like tissue outside the uterus, mainly in the pelvic area. It is associated with chronic pelvic pain and infertility, and its pathogenesis remains poorly understood. The disease is typically classified according to the revised American Fertility Society (rAFS) 4-stage surgical assessment system, although stage does not correlate well with symptomatology or prognosis. Previously identified genetic variants mainly are associated with stage III/IV disease, highlighting the need for further phenotype-stratified analysis that requires larger datasets. We conducted a meta-analysis of 15 genome-wide association studies (GWAS) and a replication analysis, including 58,115 cases and 733,480 controls in total, and sub-phenotype analyses of stage I/II, stage III/IV and infertility-associated endometriosis cases. This revealed 27 genetic loci associated with endometriosis at the genome-wide p-value threshold (P<5×10 −8 ), 13 of which are novel and an additional 8 novel genes identified from gene-based association analyses. Of the 27 loci, 21 (78%) had greater effect sizes in stage III/IV disease compared to stage I/II, 1 (4%) had greater effect size in stage I/II compared to stage III/IV and 17 (63%) had greater effect sizes when restricted to infertility-associated endometriosis cases compared to overall endometriosis. These results suggest that specific variants may confer risk for different sub-types of endometriosis through distinct pathways. Analyses of genetic variants underlying different pain symptoms reported in the UK Biobank showed that 7/9 had positive significant (p<1.28×10 3 ) positive genetic correlations with endometriosis, suggesting a genetic basis for sensitivity to pain in general. Additional conditions with significant positive genetic correlations with endometriosis included uterine fibroids, excessive and irregular menstrual bleeding, osteoarthritis, diabetes as well as menstrual cycle length and age at menarche. These results provide a basis for fine-mapping of the causal variants at these 27 loci, and for functional follow-up to understand their contribution to endometriosis and its potential subtypes.

INTRODUCTION: Long-term infection with human papillomavirus (HPV) is the cause of cervical cancer and its precursor - cervical intraepithelial neoplasia (CIN). The presence of HPV infection can be presumed in more than 99% of cases of cervical cancer worldwide. The introduction of DNA testing for the presence of HPV has increased the effectiveness of screening programs for the detection of this cancer. This study aimed to analyze the prevalence of high risk HPV DNA (HR HPV) in females from Poland. MATERIAL AND METHODS: The study was performed on 280 cervical smear samples. In this work we used the Roche Cobas 4800 HPV test to detect the HR HPV in cervical smear samples. RESULTS: 56 patients (20%) proved to be positive regarding HPV-16 DNA and 40 patients (14.28%) regarding HPV-18 DNA. In overall assessment, in 94 patients (33.57%) we detected oncogenic HPV subtypes, other than the two mentioned above. In 90 patients (32.14%) no high risk HPV was detected. CONCLUSIONS: The Roche Cobas 4800 HPV test is a viable, effective, easy and quick tool in detecting high risk HPV DNA.

Long-term infection with human papillomavirus (HPV) is the cause of cervical cancer and its precursor - cervical intraepithelial neoplasia (CIN). The presence of HPV infection can be presumed in more than 99% of cases of cervical cancer worldwide. The introduction of DNA testing for the presence of HPV has increased the effectiveness of screening programs for the detection of this cancer.

Abstract During tumorigenesis, interactions between tumor and stromal cells progressively remodel the tumor microenvironment (TME) towards pro-tumoral functions. Understanding early TME remodeling dynamics is therefore crucial for developing interceptive therapies. However, clinical samples typically provide isolated, late tumorigenesis snapshots. To overcome this limitation, we generated triple-negative breast cancer mice that develop multifocal, asynchronous tumors along a continuous luminal-to-basal transdifferentiation trajectory. Ordering spatial transcriptomes from 100+ ducts along this trajectory reveals the spatiotemporal dynamics of TME remodeling and underlying molecular mechanisms. Cancer-associated myofibroblasts (myCAFs) emerge as key players in advanced tumors, where they orchestrate pro-invasive remodeling of the tumor-stromal interface. myCAFs are conserved in patient-derived xenograft models and steer tumor trajectories towards invasive phenotypes when co-injected with tumor cells in syngeneic mice. Our study shows that temporal ordering of spatially-resolved disease snapshots unravels some of the molecular “forces” that, starting from the cell-of-origin, propel cells/microenvironments along a disease trajectory.

OBJECTIVES: The frequency of endocervical adenocarcinoma is increasing in comparison with squamous cell carcinoma and it presents a very difficult diagnostic and therapeutic problem. DESIGN: The aim of this study was: 1) Evaluation of topography of the cervical glandular intraepithelial neoplasia (CGIN) 2) An analysis of the Human Papillomavirus (HPV) infection rate in samples. MATERIALS AND METHODS: 360 amputated uterine cervix samples with histologically-proven diagnosis of cervical intraepithelial neoplasia (CIN-3) were evaluated. The coexistence of pre-invasive lesions in squamous epithelium and endocervical columnar cell were investigated. Moreover CGIN topography and retrospective histopathological analysis were determined. A polymerase chain reaction (PCR) was performed using commercially available PCR Human Papillomavirus Typing Set to detect HPV infection. RESULTS: Among 360 positive cervical intraepithelial glandular neoplasia samples (CIN-3) 71 (19.7%) showed coexisting glandular lesions (CGIN-1, 2, 3). The lesions in endocervical glandular cells of CIGN-type were distributed from the distance up to 14 mm from the surface of cervix. Most of them were located no deeper than 1 mm from the surface of canal epithelium. HPV DNA was found in more than 90 preneoplastic glandular proliferations. The frequency of oncogenic HPV-16 and 18 presence was higher than non-oncogenic HPV. CONCLUSIONS: 1. CIN-3 is associated in about 20% with cervical glandular intraepithelial neoplasia (CGIN). 2. Topography of CGIN is important in planning the management. 3. Most of CIGN are associated with HPV infection.