The COVID-19 pandemic threatens the impact of cervical cancer screening and global cervical cancer elimination goals. As cervical cancer screening programmes were adjusting to the new situation, we ...evaluated the intensity, quality, and outcomes of cervical cancer screening in Slovenia in the first seven months of the pandemic.
Historical observational study on data from a population-based cervical cancer screening registry. Number of cervical cytopathology (screening and follow-up), histopathology (diagnostic procedures, invasive procedures and number of newly diagnosed CIN2+ cases) and HPV test results from the entire Slovenian women population between January 1st and September 30th 2020 were compared to a three-year average of the years 2017–19.
A two-month screening lock-down between March 12th and May 8th 2020 resulted in an epidemic deficit of screening (-92%), follow-up (-70%), and HPV triage tests (-68%), as well as invasive diagnostic (-47%) and treatment (-15%) of cervical lesions. Time to diagnosis and treatment did not increase; times to laboratory results fluctuated but stayed within standards. Slovenia has entered the second epidemic intending to add as little as possible to the pandemic deficit of screening smears (-23%) and yearly CIN2+ cases (-10%). Women aged 30–39 were most affected, with the highest pandemic deficit of screening smears (-26%) and yearly CIN2+ cases (-19%).
The pandemic has deeply affected all levels of our lives. New vulnerable groups and inequalities have emerged that require recognition and action. To prevent long-term increases in the cervical cancer burden due to the COVID-19 pandemic, it is crucial that organised screening is maintained and monitored in settings where it can be safely and comprehensively provided.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
In the last ten years, clinical oncology has been revolutionized by the introduction of oncological immunotherapy, mainly in the form of immune checkpoint inhibitors (ICIs) that transformed the ...standard of care of several advanced solid malignancies. Using ICIs for advanced gynecological cancers has yielded good results, especially for endometrial cancer. In ovarian or cervical cancer, combining ICIs with other established agents has shown some promise. Concurrently with the clinical development of ICIs, biomarkers that predict responses to such therapy have been discovered and used in clinical trials. The translation of these biomarkers to clinical practice was somewhat hampered by lacking assay standardization and non-comprehensive reporting of biomarker status in trials often performed on a small number of gynecological cancer patients. We can expect increased use of ICIs combined with other agents in gynecological cancer in the near future. This will create a need for reliable response prediction tools, which we believe will be based on biomarker, clinical, and tumor characteristics. In this article, we review the basic biology of ICIs and response prediction biomarkers, as well as the latest clinical trials that focus on subgroup effectiveness based on biomarker status in gynecological cancer patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Certainty-Based Marking (CBM) involves asking students not only the answer to an objective question, but also how certain they are that their answer is correct. In a mixed method design employing an ...embedded approach with a quasi-experimental design, we have examined the use of CBM during a 5-week Gynaecology and Obstetrics course. The study was conducted as a non-mandatory revision exam with two additional questionnaires on Moodle. Majority of students perceive CBM as fair (78%) and useful (94%). Most students would immediately want CBM to be used for revision exams, but more practice would be needed for CBM to be used in graded exams. The lowest self-evaluation of knowledge was mostly seen by worst (less than 70% Accuracy) and best achievers (more than 90% Accuracy); the worst achievers probably have knowledge gaps, and the best achievers probably correctly guessed at least one question. Our findings conclude that CBM does not discriminate any learner type (
= 0.932) and does not change the general distribution of the exam scores, since there is no significant differences between Certainty-Based Score (
= 80.4%,
= 10.4%) and Accuracy (
= 79.8%,
= 11.1%);
(176) = 0.8327,
= 0.4061. These findings are widely applicable, as learner type study models are used extensively in education. In the future, larger samples should be studied and the implementation of CBM on question types other than MCQ should be investigated.
Background and Objectives Several reports indicate that women with von Willebrand disease (VWD) are at an increased risk of bleeding and other complications during pregnancy and childbirth. The aim ...of this study was to investigate the effect of VWD on the course of pregnancy, childbirth, and the postpartum period. Materials and Methods This was a retrospective study that compared many variables between women with VWD (n = 26) and women without VWD (n = 297,111) who gave birth between 2002 and 2016 in Slovenia. Data were obtained from the Slovenian National Perinatal Information System. Results Women with VWD were not more likely to have a miscarriage, vaginal bleeding during pregnancy, anemia, intrauterine growth restriction, or imminent premature labor. However, women with VWD were more likely to experience childbirth trauma-related bleeding (OR, 10.7; 95% CI: 1.4, 78.9), primary postpartum hemorrhage (OR, 3.7; 95% CI: 0.9, 15.8), and require blood transfusion after childbirth (OR, 16.3; 95% CI: 2.2, 120.3). No cases of stillbirth or early neonatal death were observed in women with VWD. Conclusion Although women with VWD did not demonstrate an increased risk of vaginal bleeding during pregnancy or poor fetal outcomes, they had a higher risk of primary postpartum hemorrhage and requiring blood transfusion.
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In endometrial cancer, biomarkers for preoperative identification of patients with low risk for disease progression would enable stratification according to the extent of surgery ...needed, and would avoid the complications that can be associated with radical surgery. A panel of proteins, amino acids, enzymes, and miRNA has been investigated as potential biomarkers for endometrial cancer. At the time of the manuscript submission targeted metabolomics/lipidomics approaches have not been applied to biomarker research in endometrial cancer. Using electrospray ionization–tandem mass spectrometry we quantified 163 metabolites in 126 plasma samples (61 patients with endometrial cancer, 65 control patients). Three single phosphatidylcholines were identified with significantly decreased levels in patients with endometrial cancer. A diagnostic model was defined as the ratio between acylcarnitine C16 and phosphatidylcholine PCae C40:1, the ratio between proline and tyrosine, and the ratio between the two phosphatidylcholines PCaa C42:0 and PCae C44:5; which provided sensitivity of 85.25%, specificity of 69.23%, and AUC of 0.837. Addition of smoking status further improved the constructed diagnostic model (AUC = 0.855). The presence of the major prognostic factors of deep myometrial invasion and lymphovascular invasion were also associated with altered metabolite concentrations. A prognostic model for deep myometrial invasion included the ratio between two hydroxysphingomyelins SMOH C14:1 and SMOH C24:1, and the ratio between two phosphatidylcholines PCaa C40:2 and PCaa C42:6, which provided sensitivity of 81.25%, specificity of 86.36%, and AUC of 0.857. The model for lymphovascular invasion included the ratio between two phosphatidylcholines PCaa C34:4 and PCae C38:3, and the ratio between acylcarnitine C16:2 and phosphatidylcholine PCaa C38:1, which provided sensitivity of 88.89%, specificity of 84.31%, and AUC of 0.935.
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Human papillomavirus (HPV)-based screening offers better protection against cervical cancer compared to cytology, but HPV screening assays must adhere to validation requirements of the international ...guidelines to ensure optimal performance. Allplex HPV HR Detection (Allplex) assay, launched in the late 2022, is a fully automated real-time PCR-based assay utilizing innovative technology that enables quantification and concurrent distinction of 14 high-risk HPV genotypes (HPV16,18,31,33,35,39,45,51,52,56,58,59,66 and 68). We assessed the validity of the Allplex for cervical cancer screening purposes, via comparison to a clinically validated comparator assay (Hybrid Capture 2; HC2), and through assessment of intra-laboratory reproducibility and inter-laboratory agreement. A clinical validation panel comprised of 973 residual ThinPrep samples was obtained from women aged 30-64 years participating in the organized Slovenian screening program, of these 863 were from women undergoing their regular screening visit after a previous negative screen test while 110 were from women with underlying cervical intraepithelial neoplasia grade 2 or worse (CIN2+) lesions. The Allplex's relative clinical sensitivity for detection of CIN2+ and CIN3+ were 1.01 (95%CI;0.98-1.04) and 0.98 (95%CI;0.95-1.02), compared to that of HC2. At recommended thresholds of ≥98% and ≥90%, the Allplex's clinical sensitivity and specificity (p=0.0004 and p=0.02, respectively) were non-inferior to HC2. High intra-laboratory reproducibility and inter-laboratory agreement, both overall (98.1% and 97.9%, respectively) and at genotype level (>98.7%) was observed. In addition, analytical genotype-specific performance of Allplex was compared to that of its predecessor Anyplex HPV HR; high overall agreement was observed (96.3%; kappa value 0.88), with some variations in performance. In conclusion, Allplex met all validation criteria described in the international guidelines on sensitivity, specificity and laboratory reproducibility and can be considered clinically validated for primary cervical cancer screening.
•Allplex HPV HR exhibited non inferior clinical sensitivity for CIN2+ compared to HC2.•Allplex HPV HR demonstrated high clinical accuracy in screening settings.•Allplex HPV HR exhibited high intra- and inter-laboratory reproducibility.•Allplex HPV HR can be considered validated for primary cervical cancer screening.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
7.
Importance of condom use in cervical cancer prevention Klanjšček, Jure; Pinter, Bojana; Smrkolj, Špela
European journal of obstetrics & gynecology and reproductive biology,
February 2024, 2024-02-00, Volume:
293
Journal Article
Peer reviewed
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Endometrial cancer (EC) is the most frequent gynecological malignancy in developed countries and requires a relatively invasive diagnostic evaluation and operative therapy as the primary therapeutic ...approach. Angiogenesis is one of the main processes needed for cancer growth and spread. The production of angiogenic factors (AFs) appears early in the process of carcinogenesis. The detection of AFs in plasma and tissue and a better understanding of the angiogenic properties of EC may contribute not only to earlier but also more specific diagnosis and consequently tailored and individual therapeutic approaches. AFs and their receptors also have high potential as binding sites for targeted cancer therapy. In this review, we discuss angiogenesis in EC and the characteristics of the AFs that most contribute to angiogenesis in EC. We also highlight therapeutic strategies that target angiogenesis as potential EC therapy.
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Endometrial cancer (EC) is an increasing health concern, with its growth driven by an angiogenic switch that occurs early in cancer development. Our study used publicly available datasets to examine ...the expression of angiogenesis-related genes and proteins in EC tissues, and compared them with adjacent control tissues. We identified nine genes with significant differential expression and selected six additional antiangiogenic genes from prior research for validation on EC tissue in a cohort of 36 EC patients. Using machine learning, we built a prognostic model for EC, combining our data with The Cancer Genome Atlas (TCGA). Our results revealed a significant up-regulation of IL8 and LEP and down-regulation of eleven other genes in EC tissues. These genes showed differential expression in the early stages and lower grades of EC, and in patients without deep myometrial or lymphovascular invasion. Gene co-expressions were stronger in EC tissues, particularly those with lymphovascular invasion. We also found more extensive angiogenesis-related gene involvement in postmenopausal women. In conclusion, our findings suggest that angiogenesis in EC is predominantly driven by decreased antiangiogenic factor expression, particularly in EC with less favourable prognostic features. Our machine learning model effectively stratified EC based on gene expression, distinguishing between low and high-grade cases.
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Persistent infection with human papillomavirus (HPV) causes almost all cervical precancerous lesions and cancers. Bivalent, quadrivalent, and nonavalent HPV vaccines effectively prevent high-grade ...cervical intraepithelial neoplasia (CIN3). The effectiveness of HPV vaccination against CIN3 is 97-100% in HPV-naïve populations and 44-61% in the overall population. Although HPV vaccination has substantially reduced the incidence of cervical cancers, several cases of precancerous cervical lesions in HPV-vaccinated patients have been reported. We report the clinical case of a 19-year-old woman whose first Pap smear was diagnosed as a high-grade squamous intraepithelial lesion (HSIL) after quadrivalent HPV vaccination. Colposcopy and cervical biopsy were performed, revealing HSIL/CIN3. Our multidisciplinary team decided to take a conservative approach with follow-up visits with cervical biopsies of this young patient. After six months, spontaneous regression of high-grade cervical dysplasia was observed. Although HPV immunization has shown to be extremely effective in preventing a high proportion of cervical precancerous lesions and cervical cancers, HPV vaccines do not protect against all oncogenic high-risk HPV genotypes. Consequently, healthcare providers must encourage HPV-vaccinated women to still regularly attend national cervical screening programs.
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