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Background: Determining the distribution of high-risk human papillomavirus (HR-HPV) types in histologic low-(LSIL) and high-grade (HSIL/CIN2+) squamous intraepithelial lesions through a diagnostic process in a cervical cancer prevention provides one of the key etiological factors behind further progression and persistence. Incorporating novel high-grade cervical lesion biomarkers such as p16/Ki67 dual staining (DS) alongside HPV typing has become important in detecting cervical precancers., Methods: Among 28,525 screening tests and 602 histology results, 559 cases with HR-HPV and histology results obtained from colposcopic biopsy were retrospectively analyzed, together with DS status. The χ 2 test with Bonferroni correction evaluated the differences in HR-HPV type prevalence and DS positivity across three histologic study groups., Results: A statistically significant difference in the prevalence of HPV 16 was observed between negative and HSIL/CIN2+ ( p = 0.00027) groups, as well as between the LSIL/CIN1 and HSIL/CIN2+ groups ( p = 0.00041). However, no significant difference was found between the negative and LSIL/CIN1 groups. Similarly, the DS positivity difference was significant between the negative and HSIL/CIN2+ ( p < 0.0001) and between the LSIL/CIN1 and HSIL/CIN2+ groups ( p < 0.0001), but there was no significant difference between the negative and LSIL/CIN1 groups., Conclusions: The study highlights the heterogeneous nature of HPV-related cervical pathologies, and the distinct risks associated with different cervical lesion grades, emphasizing the importance of HR-HPV type distribution and DS status.

Background: Breast cancer (BC) is the most commonly diagnosed malignant tumor in women. The disease and its subsequent treatment pose a serious burden on the quality of life of patients. Neoadjuvant chemotherapy (NAC) has become one of the crucial strategies for the management of BC. Since the identification of the vitamin D receptor (VDR) in mammary tissues, extensive mechanistic research has been conducted on its function. The expression of VDR in BC cells and the tumor microenvironment could be a new prognostic factor for BC after NAC., Patients and Methods: This observational, single-center study compared data from clinical and histopathological records of 111 female subjects with the expression of VDR in different cellular and tissue components of breast specimens obtained from surgery after NAC. VDR expression was evaluated using an immunoreactive score assigned after immunohistochemistry. Intergroup comparisons and logistic regression were used to identify associations between VDR expression and clinicopathological features of BC., Results: We found that the expression of VDR is associated with various clinical features (i.e., age, menopausal status, and NAC cycle number) and characteristics of prognostic significance, such as residual cancer burden class. Logistic regression analysis revealed that the expression of VDR in the nuclei and cytoplasm of surrounding normal mammary cells predicted vascular invasion and lymph node involvement., Conclusions: The expression of VDR in tumor cells and their microenvironment is related to the clinicopathological characteristics of BC after NAC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Streb, Łazarczyk, Hałubiec, Streb-Smoleń, Ciuruś, Ulatowska-Białas, Trzeszcz, Konopka, Hodorowicz-Zaniewska and Szpor.)

Major screening abnormalities in precolposcopic stage are tests results that imply direct referral to colposcopy (and/or expedited treatment) without performing additional high-grade squamous intraepithelial lesions or worse (HSIL+) risk selection testing. Currently, both clinically validated HSIL+ risk selection tests, reflex cytology and reflex p16/Ki67 dual staining (DS), are being compared for use in primary human papillomavirus (HPV)-based screening to avoid possible overtreatment, but there is still no sufficient data available for their performance. Among 30 066 liquid-based cervical cancer screening tests results, a group of 332 women was selected with available high-risk types of HPV tests results with 16/18 limited genotyping, liquid-based cytology, DS, and histology results from standardized colposcopy with biopsy. In HPV 16/18+ cases, three triage approaches were retrospectively analyzed. Predictive values for detection of HSIL+ were calculated and number of colposcopies required in each strategy. Both triage models with DS used (reflex cytology followed by DS, and reflex DS alone in all cases) had significantly higher positive predictive value for HSIL+ than strategy with reflex cytology alone (44.2%/45.7% vs. 28.3%; p < 0.0001). In models with DS, less colposcopies were required (95/92 vs. 152) and less colposcopies were needed per HSIL+ detection (2.26/2.19 vs. 3.54). Only one HSIL+ case was missed in both triage models with DS incorporation. p16/Ki67 dual-stain may be an effective, alone or combined with cytology, triage test to detect HSIL+ in patients with major screening abnormalities in primary HPV-based cervical cancer screening. Performing cytology as the first triage test improves the strategy by enabling referrals to expedited treatment in selected cases., (© 2024 Wiley Periodicals LLC.)

The introduction of primary human papillomavirus (HPV) cervical cancer screening requires the implementation of an appropriate triage strategy that will be effective in detecting high-grade cervical disease without losing diagnostic specificity. From the 30.066 screening tests results, a total of 1086 with available high-risk human papillomavirus (HRHPV) with limited genotyping, cytology, and p16/Ki67 dual-stain were selected. Two triage strategies for primary HPV screening were analyzed retrospectively based on the study group. Performance characteristics for p16/Ki67 and cytology triage in the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+) were calculated, detected in colposcopic biopsy. In HPV16/18-positive cases, primary HPV with p16/Ki67 triage was significantly more specific than cytology (53.1%/16.8% for CIN2+; p < 0.0001; 45.9%/17.0% for CIN3+; p < 0.0001), with yielded sensitivity (95.7%/84.8% for CIN2+; p = 0.0955; 100.0%/87.5% for CIN3+; p = 0.0832). In other HRHPV-positive cases (N16/N18), p16/Ki67 triage was also significantly higher specific (51.3%/15.3% for CIN2+; p < 0.0001; 44.5%/16.5% for CIN3+; p < 0.0001), with sensitivity (92.3%/74.4% for CIN2+; p = 0.0522; 90.9%/81.8% for CIN3+; p = 0.5637). Diagnostic predictive values were significantly higher for p16/Ki67 triage with the highest PPV in HPV16/18-positive cases for CIN2+ (45.4%; 95% confidence interval [CI]: 35.2-55.8; p < 0.0001) and very high NPV in all HPV-positive cases regardless of detected genotype (96.3%-100.0%). The risk (1-NPV) for CIN3+ in HRHPV16/18-positive/p16/Ki67-negative women was 0.0%. Superior diagnostic performance compared to cytology for detecting cervical cancer precursors indicates that p16/Ki67 dual-immunostain may be a highly effective tool of triage in primary HPV screening with limited HPV 16/18 genotyping in secondary cervical cancer prevention., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: In the context of primary HPV cervical cancer screening, the identification of minor screening abnormalities necessitates triage tests to optimize management and mitigate overtreatment. Currently, reflex cytology and reflex p16/Ki67 dual-stain (DS) are under scrutiny for their applicability in primary HPV-based screening. However, there remains a dearth of comprehensive data for comparing their performance., Methods: Among 30,066 results from liquid-based cervical cancer screening tests, a cohort of 332 cases was meticulously selected based on available high-risk human papillomavirus (HPV) test results, limited genotyping for HPV 16 and 18, liquid-based cytology, DS, and histology outcomes from standardized colposcopy with biopsy. For cases positive for 12 other high-risk HPV genotypes, three retrospective triage approaches were analyzed. We computed the positive predictive value (PPV) for the detection of high-grade squamous intraepithelial lesions or worse (HSIL+)., Results: Both triage models employing DS (reflex cytology followed by DS and reflex DS alone in all cases) exhibited significantly higher PPV for HSIL+ compared to the strategy with reflex cytology alone (35.9%/33.3% vs. 18.8%; p < 0.0001). Additionally, these DS-based models showed higher negative predictive values (NPV) (100%/96.2% vs. 69.2%; p = 0.0024/0.0079). In the DS-inclusive models, fewer colposcopies were necessitated (103/102 vs. 154), and fewer cases of HSIL+ were overlooked (0/3 vs. 8)., Conclusions: Our findings suggest that p16/Ki67 dual-stain, either as a standalone or combined triage test, holds promise for the effective detection of HSIL+ in patients with minor screening abnormalities in primary HPV-based cervical cancer screening.

There is accumulating evidence on the perinatal aspects of COVID-19, but available data are still insufficient. The reports on perinatal aspects of COVID-19 have been published on a small group of patients. Vertical transmission has been noted. The SARS-CoV-2 genome can be detected in umbilical cord blood and at-term placenta, and the infants demonstrate elevated SARS-CoV-2-specific IgG and IgM antibody levels. In this work, the analysis of clinical characteristics of RT-PCR SARS-CoV-2-positive pregnant women and their infants, along with the placental pathology correlation results, including villous trophoblast immunoexpression status for SARS-CoV-2 antibody, is presented. RT-PCR SARS-CoV-2 amniotic fluid testing was performed. Neonatal surveillance of infection status comprised RT-PCR testing of a nasopharyngeal swab and the measuring of levels of anti-SARS-CoV-2 in blood serum. In the initial study group were 161 pregnant women with positive test results. From that group, women who delivered during the hospital stay were selected for further analysis. Clinical data, laboratory results, placental histomorphology results, and neonatal outcomes were compared in women with immunohistochemistry (IHC)-con SARS-CoV-2-positive and IHC SARS-CoV-2-negative placentas (26 cases). A positive placental immunoprofile was noted in 8% of cases ( n = 2), whereas 92% of cases were negative ( n = 24). Women with placental infection proven by IHC had significantly different pathological findings from those without. One infected neonate was noted ( n = 1; 4%). Infection was confirmed in perinatal autopsy, as there was the intrauterine fetal demise. The potential course of the infection with the risk of vertical transmission and implications for fetal-neonatal condition is critical for proper clinical management, which will involve comprehensive, multidisciplinary perinatal care for SARS-CoV-2-positive patients.

Background: Infection with SARS-CoV-2 during pregnancy can lead to a severe condition in the patient, which is challenging for obstetricians and anaesthesiologists. Upon severe COVID-19 and a lack of improvement after multidrug therapy and mechanical ventilation, extracorporeal membrane oxygenation (ECMO) is introduced as the last option. Such treatment is critical in women with very preterm pregnancy when each additional day of the intrauterine stay is vital for the survival of the newborn., Case Presentation: We report a case of a 38-year-old woman at 27 weeks of gestation treated with multidrug therapy and ECMO. The woman was admitted to the intensive care unit (ICU) with increasing fever, cough and dyspnoea. The course of the pregnancy was uncomplicated. She was otherwise healthy. At admission, she presented with severe dyspnoea, with oxygen saturation (SpO2) of 95% on passive oxygenation, heart rate of 145/min, and blood pressure of 145/90. After confirmation of SARS-CoV-2 infection, she received steroids, remdesivir and convalescent plasma therapy. The foetus was in good condition. No signs of an intrauterine infection were visible. Due to tachypnea of 40/min and SpO2 of 90%, the woman was intubated and mechanically ventilated. Due to circulatory failure, the prothrombotic activity of the coagulation system, further saturation worsening, and poor control of sedation, she was qualified for veno-venous ECMO. An elective caesarean section was performed at 29 weeks on ECMO treatment in the ICU. A preterm female newborn was delivered with an Apgar score of 7 and a birth weight of 1440 g. The newborn had no laboratory or clinical evidence of COVID-19. The placenta showed the following pathological changes: large subchorionic haematoma, maternal vascular malperfusion, marginal cord insertion, and chorangioma., Conclusions: This case presents the successful use of ECMO in a pregnant woman with acute respiratory distress syndrome in the course of severe COVID-19. Further research is required to explain the aetiology of placental disorders (e.g., maternal vascular malperfusion lesions or thrombotic influence of COVID-19). ECMO treatment in pregnant women remains challenging; thus, it should be used with caution. Long-term assessment may help to evaluate the safety of the ECMO procedure in pregnant women., (© 2021. The Author(s).)

Recently, cervical cancer rates elevation has been noted in women aged 20-39 years in regions with a very high human development index (HDI). The onset of cancer elevation rates is observed in the age range of 25-29 years, which should necessitate effective precancer screening in younger age groups, including those <25 years. From 30.066 liquid-based screening tests results ( n = 30.066), 3849 liquid-based cytology, 1321 high-risk human papillomavirus (HRHPV) and 316 p16/Ki67 performed in women <30 years were selected. Performance characteristics were calculated for three screening models: primary HRHPV with p16/Ki67 triage, primary cytology with reflex HPV and primary cytology alone. Primary HRHPV with p16/Ki67 triage was significantly more sensitive in high-grade squamous intraepithelial lesion quantified with cervical intraepithelial neoplasia grade 2 or worse [HSIL(CIN2+)] detection than cytology with reflex HRHPV and cytology alone (83.3% vs. 70.8%/45.8%) and had significantly higher diagnostic predictive values (PPV:29.4%/21.3%/22.9%; NPV:91.7%/82.9%/82.2%, respectively at CIN2+ threshold). The number of colposcopies per HSIL(CIN2+) detection indices was 3.4, 4.7 and 4.4, respectively. Primary HPV testing in women <30 years with p16/Ki67 triage of HPV-positive cases might be an effective cervical cancer screening strategy for HSIL(CIN2+) detection with superior diagnostic performance when compared with primary cytology-based models. Women <25 years might also benefit from an introduction to a more sensitive screening approach.

The baseline data from the private-based opportunistic cervical cancer screening with HRHPV14, liquid-based cytology (LBC) and p16/Ki67 testing, and its quality assessment/quality control (QA/QC) tools are lacking. The age-stratified analysis of 30,066 screening tests results in a Polish population, including the investigation of HRHPV14 status, LBC, and p16/Ki67 dual-staining reporting rates, along with immediate histopathologic correlations, was conducted. For cytopathologic QA/QC, the College of American Pathologists (CAP) benchmarks and enhanced safety protocol were used. The NILM/ASC-US/LSIL/ASC-H/HSIL/AGC reporting rates were 93.9/3.4/2.0/0.22/0.24/0.11, respectively, with correlating HRHPV14-positive rates of 8.4/48.9/77.2/84.6/90.7/26.7. The reporting rates for HSIL (CIN2+) in HRHPV-positive women with NILM/ASC-US/LSIL/ASC-H/HSIL/AGC referred for a colposcopy with biopsy were 19.1/25.8/22.5/12.4/19.1/1.1% of the total HSIL (CIN2+). In total, of the 1130 p16/Ki67 tests, 30% were positive. In NILM HRHPV14-positive women with available histology result, HSIL(CIN2+) was detected in 28.3% of cases. In the first such large-scale Polish study presenting HRHPV14, informed LBC and HSIL (CIN2+) results, the reporting rates were highly consistent with data from American and other CAP-certified laboratories, confirming the possibility of using the 2019 ASCCP risk-based guidelines as one of the screening strategies outside of the US, in conditions of proper QA/QC. The private-based screening model can be effective in cervical cancer prevention, particularly in countries with low population coverage of public funds-based systems.

Optimal management of intrauterine infection to avoid serious adverse perinatal outcomes entails prompt administration of antibiotics and consideration of early delivery of the fetus to remove the focus of infection. We report an unusual case of preterm chorioamnionitis which did not improve with sensitive antibiotics, or delivery of the fetus, and ultimately required an emergency hysterectomy to save the mother's life. Interestingly, subsequent histopathological analysis of the post-hysterectomy specimen did not reveal myometrial necrosis or infectious microorganisms. The placental pathological examination, on the other hand, showed evidence of necrotising chorioamnionitis accompanied by a rarely reported lesion: acute villitis with abundant intravascular Escherichia coli , a finding which is strongly associated with fetal demise and adverse maternal outcomes.

The Polish Society of Colposcopy and Cervical Pathophysiology (PTKiPSM) together with the Polish Society of Gynecologists and Obstetricians (PTGiP) issued a final summary of interim guidelines for secondary cervical cancer prevention during the SARS-CoV-2 pandemic based on the analysis of the latest directional publications and the authors' own experiences. The aim of the summary is to facilitate the implementation of the most effective possible screening of cervical precancerous lesions and cervical cancer due to temporary significant limitation of screening as a consequence of the ongoing epidemiological threat. These final guidelines are taking into account the 2020 call of the World Health Organization (WHO) for global epidemiological elimination of cervical cancer. The guidelines supplement the interim guidelines of PTKiPSM and PTGiP announced in March 2020 on the possible deferral of diagnostic and therapeutic procedures in patients with abnormal screening tests results in secondary prevention of cervical cancer in current pandemic.

The Polish Society of Gynecologists and Obstetricians and Polish Society of Colposcopy and Cervical Pathophysiology Interim Guidelines goal at aiding gynecologists in providing a cervical cancer prevention care during the evolving SARS-CoV-2 pan-demic. Presented guidelines were developed on a review of limited data and updated when new relevant publications were revealed. Timing for deferrals of diagnostic-therapeutic procedures were mostly covered in the guidelines. Also, a support for the existing Polish recommendations on abnormal screening results in a subject of minor and major screening abnor-malities terminology were given. The guidelines are obligatory for the specified COVID-19 pandemic period only and they might be changed depending on the new available evidence.

The Polish Society of Colposcopy and Cervical Pathophysiology and the Polish Society of Gynecologists and Obstetricians provide comprehensive guidelines for colposcopy practice in secondary cervical cancer prevention in Poland. This part of the guidelines, developed by the clinical experts of the Working Group No. 1 (WG1), concerns the colposcopy protocols with the main aim of algorithmizing the procedure, together with all procedure-related processes. The detailed analysis of strong scientific evidence and an extensive literature review of current international colposcopic recommendations were carried out, with also a broad investigation of recently ongoing dynamic changes in national health systems. The attention to colposcopic limitations also occurring in Polish conditions was kept. The overriding goal was the recommended obligatory minimal colposcopy approach introduction. To enhance the standard of colposcopy, adjustment of a precolposcopic assessment, a performance technique, types of used biopsies, as well as the procedure documentation was made. Elements of the risk-based stratification for the increased risk of developing cervical cancer was also included if it was applicable for that part of the guidelines. Comprehensive colposcopy guidelines are a step towards the ongoing era of a precision medicine in cervical cancer prevention in Poland.

Objective: As the patterns and frequency of maternal and clinical conditions and outcomes and gross and histological placental features and lesions vary with gestational age at delivery, we aimed to study the impact of these changes on the placental diagnosis, hoping to uncover potential novel clusters of gestational age-associated clinical and pathological diagnoses., Design: Retrospective statistical analysis of clinicoplacental database., Population: We analyzed 28 clinical (maternal and fetal) and 49 gross and microscopic placental variables from 3294 consecutively signed placentas received between 2001 and 2012, divided into three gestational age groups: 16-27 weeks, 697 cases; 28-36 weeks, 1365 cases; and 37+ weeks, in all 1232 cases., Methods: Classical statistics by chi-squared and Fischer's tests, and the Ward agglomerative hierarchical clustering and multidimensional scaling techniques, were used., Results: The placental phenotypes clustered statistically significantly with severe preeclampsia in the second trimester; preterm premature rupture of membranes, placental abruption, and fetal growth restriction in the whole third trimester; and abnormally invasive placenta, thick meconium, maternal diabetes mellitus, and substance abuse in term pregnancies., Conclusions: The applied statistical analyses made it possible to simultaneously compare the strength of clinicoplacental associations separately in three pregnancy intervals. Placental clinicopathological associations are strongest for the second trimester, i.e. severe preeclampsia and preterm ascending infection-related conditions, but were not significant for other pregnancy complications such as mild preeclampsia, chronic hypertension, diabetes mellitus, or umbilical cord compromise., (© 2014 Nordic Federation of Societies of Obstetrics and Gynecology.)