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Screening for human papillomavirus (HPV) infection is more effective in reducing the incidence of cervical cancer than screening using Pap smears. Moreover, HPV testing can be done on a vaginal sample self-taken by a woman, which offers an opportunity to improve screening coverage. However, the clinical accuracy of HPV testing on self-samples is not well-known. We assessed whether HPV testing on self-collected samples is equivalent to HPV testing on samples collected by clinicians. We identified relevant studies through a search of PubMed, Embase, and CENTRAL. Studies were eligible for inclusion if they fulfilled all of the following selection criteria: a cervical cell sample was self-collected by a woman followed by a sample taken by a clinician; a high-risk HPV test was done on the self-sample (index test) and HPV-testing or cytological interpretation was done on the specimen collected by the clinician (comparator tests); and the presence or absence of cervical intraepithelial neoplasia grade 2 (CIN2) or worse was verified by colposcopy and biopsy in all enrolled women or in women with one or more positive tests. The absolute accuracy for finding CIN2 or worse, or CIN grade 3 (CIN3) or worse of the index and comparator tests as well as the relative accuracy of the index versus the comparator tests were pooled using bivariate normal models and random effect models. We included data from 36 studies, which altogether enrolled 154 556 women. The absolute accuracy varied by clinical setting. In the context of screening, HPV testing on self-samples detected, on average, 76% (95% CI 69–82) of CIN2 or worse and 84% (72–92) of CIN3 or worse. The pooled absolute specificity to exclude CIN2 or worse was 86% (83–89) and 87% (84–90) to exclude CIN3 or worse. The variation of the relative accuracy of HPV testing on self-samples compared with tests on clinician-taken samples was low across settings, enabling pooling of the relative accuracy over all studies. The pooled sensitivity of HPV testing on self-samples was lower than HPV testing on a clinician-taken sample (ratio 0·88 [95% CI 0·85–0·91] for CIN2 or worse and 0·89 [0·83–0·96] for CIN3 or worse). Also specificity was lower in self-samples versus clinician-taken samples (ratio 0·96 [0·95–0·97] for CIN2 or worse and 0·96 [0·93–0·99] for CIN3 or worse). HPV testing with signal-based assays on self-samples was less sensitive and specific than testing on clinician-based samples. By contrast, some PCR-based HPV tests generally showed similar sensitivity on both self-samples and clinician-based samples. In screening programmes using signal-based assays, sampling by a clinician should be recommended. However, HPV testing on a self-sample can be suggested as an additional strategy to reach women not participating in the regular screening programme. Some PCR-based HPV tests could be considered for routine screening after careful piloting assessing feasibility, logistics, population compliance, and costs. The 7th Framework Programme of the European Commission, the Belgian Foundation against Cancer, the International Agency for Research on Cancer, and the German Guideline Program in Oncology.

Radical hysterectomy and complete pelvic lymphadenectomies are the most commonly performed procedures for women with early-stage cervical cancer. Sentinel lymph node (SLN) mapping could be an alternative to routine pelvic lymphadenectomy, aiming to diagnose accurately nodal extension and decrease lymphatic morbidity. To compare 3-year disease-free survival and health-related quality of life after SLN biopsy or SLN biopsy + pelvic lymphadenectomy in early cervical cancer. We hypothesize that disease-free survival is non-inferior and health-related quality of life superior after SLN biopsy compared with SLN biopsy + pelvic lymphadenectomy. International, randomized, multicenter, single-blind trial. The study will be run by teams trained to carry out SLN biopsy, belonging to clinical research cooperative groups or recognized as experts in this field. Patients with an optimal mapping (Memorial Sloan Kettering Cancer Center [MSKCC] criteria) and a negative frozen section will be randomized 1:1 to SLN biopsy only or SLN biopsy + pelvic lymphadenectomy. Patients with early stages (Ia1 with lymphovascular invasion to IIa1) of disease. Histological types are limited to squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma. Main endpoint will be co-primary endpoint, associating 3-year disease-free survival and quality of life (QLQ-C30 and QLQ-CX24). 950 patients need to be randomized. Estimated dates for completing accrual and presenting results: study started on Q2 2018, last accrual is scheduled for Q2 2021, and last follow-up in Q2 2026. ClinicalTrials.gov identifier: NCT03386734.

Endometrial cancer (EC) is the most common cancer affecting the female reproductive organs in higher-income states. Apart from reproductive factors and excess weight, genetic predisposition is increasingly recognized as a major factor in endometrial cancer risk. Endometrial cancer is genetically heterogeneous: while a subgroup of patients belongs to cancer predisposition syndromes (most notably the Lynch Syndrome) with high to intermediate lifetime risks, there are also several common genomic polymorphisms contributing to the spectrum of germline predispositions. Germline variants and somatic events may act in concert to modulate the molecular evolution of the tumor, where mismatch-repair deficiency is common in endometrioid endometrial tumors whereas homologous recombinational repair deficiency has been described for non-endometrioid endometrial tumors. In this review, we will survey the currently known genomic predispositions for endometrial cancer and discuss their relevance for clinical management in terms of counseling, screening and novel treatments.

Background Exercise training is beneficial in enhancing physical function and quality of life in cancer patients. Its comprehensive implementation remains challenging, and underlying cardiopulmonary adaptations are poorly investigated. This randomized controlled trial examines the implementation and effects of home-based online training on cardiopulmonary variables and physical activity. Methods Of screened post-surgical patients with breast, prostate, or colorectal cancer, 148 were randomly assigned (1:1) to an intervention (2 × 30 min/week of strength-endurance training using video presentations) and a control group. All patients received activity feedback during the 6-month intervention period. Primary endpoint was change in oxygen uptake after 6 months. Secondary endpoints included changes in cardiac output, rate pressure product, quality of life (EORTC QoL-C30), C-reactive protein, and activity behavior. Results One hundred twenty-two patients (62 intervention and 60 control group) completed the study period. Change in oxygen uptake between intervention and control patients was 1.8 vs. 0.66 ml/kg/min (estimated difference after 6 months: 1.24; 95% CI 0.23 to 2.55; p  = 0.017). Rate pressure product was reduced in IG (estimated difference after 6 months: − 1079; 95% CI − 2157 to − 1; p  = 0.05). Physical activity per week was not different in IG and CG. There were no significant interaction effects in body composition, cardiac output, C-reactive protein, or quality of life. Conclusions Home-based online training among post-surgery cancer patients revealed an increase of oxygen uptake and a decrease of myocardial workload during exercise. The implementation of area-wide home-based training and activity feedback as an integral component in cancer care and studies investigating long-term effects are needed. Trial registration DRKS-ID: DRKS00020499 ; Registered 17 March 2020.

Introduction Twin pregnancies impose greater cardiovascular demands than singleton gestations, potentially increasing long‐term cardiovascular risk even in the absence of hypertensive disorders. Nevertheless, longitudinal assessments of maternal hemodynamics in uncomplicated twin pregnancies remain limited, and most available studies focus solely on the antenatal period. Chorionicity has been shown to markedly influence cardiovascular adaptation during twin gestation. This study aimed to investigate whether distinct hemodynamic adaptations occur in twin compared with singleton pregnancies during late gestation, 1 day and 6 weeks postpartum. Material and Methods In this prospective longitudinal cohort study conducted at Hannover Medical School from 08/24 to 05/2025, 36 women with twin pregnancies (8 monochorionic (MC), 28 dichorionic (DC)) and 37 with singleton pregnancies underwent noninvasive hemodynamic assessment at 34 weeks' gestation, 1 day postpartum, and 6 weeks postpartum. Results MC twin pregnancies exhibited significantly higher cardiac output (MC: 7.72 L/min; DC: 5.62 L/min; S: 6.27 L/min; p = 0.01) and lower systemic vascular resistance (MC: 958.83 dynes × s/cm5; DC: 1206.86 dynes × s/cm5; S: 1119.45 dynes × s/cm5; p = 0.01) during the third trimester, with a similar hemodynamic pattern appearing to persist in the postpartum period. MC twins also showed significant decreases in heart rate (T1: 86.37 bpm; T2: 77.73 bpm; T3: 66.67 bpm; p = 0.002), mean arterial pressure (T1: 93.0 mmHg; T2: 85.5 mmHg; T3: 78.0 mmHg; p = 0.03), and inotropism postpartum (T1: 1.92 W/m2; T2: 1.67 W/m2; T3: 1.54 W/m2; p = 0.04), whereas DC twins demonstrated a trend to higher stroke volume (T1: 69.6 mL; T2: 80.31 mL; T3: 82.63 mL; p = 0.01) and gradual increase of vascular resistance (T1: 1206.86 dynes × s/cm5; T2:1099.86 dynes × s/cm5; T3: 1426.78 dynes × s/cm5; p = 0.08). Conclusions Monochorionic twin pregnancies are characterized by elevated cardiac output and reduced vascular resistance in late pregnancy, with a similar hemodynamic pattern appearing to persist in the postpartum period. This persistent cardiovascular strain may underlie the elevated short‐term cardiovascular risk observed after twin births. Our findings highlight the need for larger longitudinal studies to explore the transition from physiological adaptation to potential cardiovascular maladaptation.

Aim There is currently no protocol for classifying patients with HPV persistence and preoperative stenosis of the cervical canal. This has a significant impact on cytology results, colposcopy results and the possibility of obtaining reliable cervical histology outcomes. Our analysis clearly shows that colposcopy and cytology underestimate the histological results in patients with limited visibility due to the presence of a type 3 transformation zone (TZ). Our analysis revealed a significant discrepancy between the colposcopy and cytology results and the histological outcomes. Insufficient colposcopy led to the underdiagnosis of dysplastic lesions in patients with a type 3 TZ and cervical stenosis. In the case of repeated cytological abnormalities and inadequate colposcopy examination, it is crucial to perform a diagnostic conization to exclude high-grade dysplastic changes and cervical carcinoma. Methods We conducted a retrospective analysis of 1,021 conizations performed in tertiary care hospital in Wolfsburg, Germany between 2014 and 2020. Of these surgical procedures, 89 were diagnostic conizations. In our analysis, we defined diagnostic conization as a procedure performed when there is HPV persistence and repeated cytologic abnormalities in combination with a type 3 TZ, and when it is not possible to retrieve a relevant cervical histology sample. Results In this period, 8.7% of all conizations were diagnostic excisions. We found histological abnormalities in 48 of 89 patients (53.9%). The histological examination of the excised cone revealed high-grade cervical intraepithelial neoplasia (CIN/HSIL) in 9 patients (10.1%) and CIN 2+ (HSIL) in 23 out of the 89 patients (25.8%). Two cases of early-stage cervical carcinoma (FIGO IA1 and FIGO IA2) were confirmed (2.3%). Conclusion Patients with cervical stenosis, high-risk HPV persistence and repeated cytological abnormalities are at high risk of undetected high-grade cervical dysplasia. Histologic confirmation must be ensured in this patient consultation and this can be achieved by performing diagnostic excisions.

Breast cancer is the most prevalent malignancy amongst women worldwide while ovarian cancer represents the leading cause of death among gynecological malignancies. Women suffering from these cancers displayed heightened rates of major depressive disorder, and antidepressant treatment with selective serotonin reuptake inhibitors (SSRIs) is frequently recommended. Recently, narrative reviews and meta-analyses showed increased recurrence risks and mortality rates in SSRI-treated women with breast and ovarian cancer. We therefore examined whether three commonly prescribed SSRIs, fluoxetine, sertraline and citalopram, affect proliferation or glucose uptake of human breast and ovarian cancer cell lines characterized by different malignancies and metastatic potential. SSRI treatment or serotonin stimulation with therapeutically relevant concentrations over various time periods revealed no consistent dose- or time-dependent effect on proliferation rates. A marginal, but significant increase in glucose uptake was observed in SK-OV-3 ovarian cancer cells upon fluoxetine or sertraline, but not citalopram treatment. In three breast cancer cell lines and in two additional ovarian cancer cell lines no significant effect of SSRIs on glucose uptake was observed. Our data suggest that the observed increase in recurrence- and mortality rates in SSRI-treated cancer patients is unlikely to be linked to antidepressant therapies.

Resistance to the currently available treatment paradigms is one of the main factors that contributes to poor outcomes in patients with advanced cervical cancer. Novel targeted therapy approaches might enhance the patient’s treatment outcome and are urgently needed for this malignancy. While chimeric-antigen receptor (CAR)-based adoptive immunotherapy displays a promising treatment strategy for liquid cancers, their use against cervical cancer is largely unexplored. This study used alpharetroviral SIN vectors to equip natural killer (NK) cells with a third-generation CAR (including CD28 and 4-1BB co-stimulatory domains) targeting Mesothelin, which was identified to be highly expressed on primary human cervical cancer tissues and cervical cancer cell lines in this and other studies. Anti-Mesothelin CAR-NK cells demonstrated high cytotoxicity against cervical cancer cells in 2D and 3D culture models, which corresponded to increased degranulation of CAR-NK-92 cells upon exposure to Mesothelin + target cells. Mesothelin - cervical cancer cells were generated by CRISPR-Cas9-mediated knockout and used to show target antigen specificity of anti-Mesothelin CAR-NK-92 cells and primary NK cells derived from different healthy donors in co-culture experiments. Combination of anti-Mesothelin CAR-NK-92 cells with chemotherapy revealed increased elimination of cancer cells as compared to monotherapy settings. Our findings indicate the promise of anti-Mesothelin CAR-NK cells as a potential treatment option against cervical cancer, as well as other Mesothelin + malignancies.

Introduction: Maternal body mass index and gestational weight gain (GWG) are important factors for maternal and neonatal health. The objective of this study was to assess women’s knowledge and examine adherence to the Institute of Medicine (IOM) criteria for weight gain during pregnancy by evaluating the information received from obstetricians and women’s knowledge about GWG. Methods: This is an analytical semi-longitudinal observational study. Weight data from a not consecutive convenience sample of 389 women who gave birth at the Hannover Medical School in the period from 08/2020 to 07/2021 were taken from their maternal records. Immediately after giving birth the whole collective (n=389) was asked to participate in a questionnaire study including questions that were taken from the EMat Health Survey inquiring about their knowledge and received information about GWG and about their eating behavior. Here a subset of 202 women participated. Results: 65% of the participants who answered the questionnaire reported that they had not been informed by their obstetrician about GWG recommendations. Additionally, a minority of women knew the correct IOM GWG category based on their pre-pregnancy weight. Meeting the IOM GWG guidelines did not depend on whether or not women received GWG recommendations or knew about the correct GWG category. The majority of women were not concerned about gaining too much weight during pregnancy. 20.7% of all women participating in the study were affected by obesity pre-pregnancy. According the IOM criteria for GWG 50.4% gained too much weight. The proportion of women exceeding IOM recommendations was highest in women with pre-pregnancy overweight and obesity (67%). Discussion: Weight gain outside of the IOM recommendations is widespread in our survey. Information received and knowledge about GWG recommendations were inadequate in our sample. Considering the fact that GWG outside recommended ranges can contribute to short- and long-term health complications, especially when a woman enters pregnancy already with overweight or obesity, identifying ways of achieving a healthier GWG is warranted.

Ovarian cancer is the most common cause of gynecological cancer-related death in the developed world. Disease recurrence and chemoresistance are major causes of poor survival rates in ovarian cancer patients. Ovarian cancer stem cells (CSCs) were shown to represent a source of tumor recurrence owing to the high resistance to chemotherapy and enhanced tumorigenicity. Chimeric antigen receptor (CAR)-based adoptive immunotherapy represents a promising strategy to reduce the risk for recurrent disease. In this study, we developed a codon-optimized third-generation CAR to specifically target CD44, a marker widely expressed on ovarian cancer cells and associated with CSC-like properties and intraperitoneal tumor spread. We equipped NK-92 cells with the anti-CD44 CAR (CD44NK) and an anti-CD19 control CAR (CD19NK) using lentiviral SIN vectors. Compared to CD19NK and untransduced NK-92 cells, CD44NK showed potent and specific cytotoxic activity against CD44-positive ovarian cancer cell lines (SKOV3 and OVCAR3) and primary ovarian cancer cells harvested from ascites. In contrast, CD44NK had less cytotoxic activity against CD44-negative A2780 cells. Specific activation of engineered NK cells was also demonstrated by interferon-γ (IFNγ) secretion assays. Furthermore, CD44NK cells still demonstrated cytotoxic activity under cisplatin treatment. Most importantly, the simultaneous treatment with CD44NK and cisplatin showed higher anti-tumor activity than sequential treatment.