Cervical precancer and cancer incidence among insured women with and without HIV in South Africa.

HIV infection increases the risk of developing cervical cancer; however, longitudinal studies in sub-Saharan Africa comparing cervical cancer rates between women living with HIV (WLWH) and women without HIV are scarce. To address this gap, we compared cervical precancer and cancer incidence rates between WLWH and women without HIV in South Africa using reimbursement claims data from a medical insurance scheme from January 2011 to June 2020. We used Royston-Parmar flexible parametric survival models to estimate cervical precancer and cancer incidence rates as a continuous function of age, stratified by HIV status. Our study population consisted of 518 048 women, with exclusions based on the endpoint of interest. To analyse cervical cancer incidence, we included 517 312 women, of whom 564 developed cervical cancer. WLWH had an ~3-fold higher risk of developing cervical precancer and cancer than women without HIV (adjusted hazard ratio for cervical cancer: 2.99; 95% confidence interval [CI]: 2.40-3.73). For all endpoints of interest, the estimated incidence rates were higher in WLWH than women without HIV. Cervical cancer rates among WLWH increased at early ages and peaked at 49 years (122/100 000 person-years; 95% CI: 100-147), whereas, in women without HIV, incidence rates peaked at 56 years (40/100 000 person-years; 95% CI: 36-45). Cervical precancer rates peaked in women in their 30s. Analyses of age-specific cervical cancer rates by HIV status are essential to inform the design of targeted cervical cancer prevention policies in Southern Africa and other regions with a double burden of HIV and cervical cancer.

Handheld vital microscopy for the identification of microcirculatory alterations in cervical intraepithelial neoplasia and cervical cancer.

BACKGROUND: Ninety percent of cervical cancer (CC) diagnoses and deaths occur in low and middle-income countries (LMICs). Especially in these countries, where human and material resources are limited, there is a need for real-time screening methods that enable immediate treatment decisions (i.e., 'see and treat'). OBJECTIVE: To evaluate whether handheld vital microscopy (HVM) enables real-time detection of microvascular alterations associated with cervical intraepithelial neoplasia (CIN) and CC. METHODS: A cross-sectional study was conducted in an oncologic hospital and outpatient clinic, and included ten healthy controls, ten women with CIN, and ten women with CC. The microvasculature was assessed in four quadrants of the uterine cervix using HVM. The primary outcome was the presence of abnormal angioarchitecture (AA). Secondary outcomes included capillary loop density (CD), total vessel density (TVD), functional capillary density (FCD), and the proportion of perfused vessels (PPV). RESULTS: 198 image sequences of the cervical microvasculature were recorded. Compared to healthy controls, significantly more abnormal image sequences were observed in women with high-grade CIN (11 % vs. 44 %, P < 0.001) and women with CC (11 % vs. 69 %, P < 0.001). TVD, FCD, and PPV were lower in women with CIN and CC. CONCLUSIONS: HVM enables easy, real-time, non-invasive assessment of cervical lesions through the detection of microvascular alterations. Thereby, HVM potentially provides an opportunity for point-of-care screening, which may enable immediate treatment decisions (see and treat) and reduce the number of unnecessary surgical interventions.

Pattern A endocervical adenocarcinomas with ovarian metastasis are indolent and molecularly distinct from destructively invasive adenocarcinomas.

AIMS: The invasive pattern in HPV-associated endocervical adenocarcinoma (HPVA) has prognostic value. Non-destructive (pattern A) HPVA has excellent prognosis mirroring adenocarcinoma in-situ (AIS). However, the rare occurrence of ovarian spread in these tumours suggests aggressiveness in a subset of patients with these otherwise indolent lesions. We hypothesise that AIS/pattern A HPVA with ovarian metastases are biologically different than metastatic destructively invasive HPVA. METHODS AND RESULTS: Samples from patients with HPVA and synchronous or metachronous metastases were retrieved and reviewed to confirm diagnosis and determine the Silva pattern in the primary lesion. For each case, normal tissue, cervical tumour and at least one metastasis underwent comprehensive sequencing using a 447-gene panel. Pathogenic single-nucleotide variants and segmental copy-number alterations (CNA), tumour mutational burden and molecular signatures were evaluated and compared between primary and metastases and among invasive pattern categories. We identified 13 patients: four had AIS/pattern A primaries, while nine had pattern B/C tumours. All AIS/pattern A lesions had metastasis only to ovary; 50% of patients with ovarian involvement, regardless of invasive pattern, also had involvement of the endometrium and/or fallopian tube mucosa by HPVA. In the ovary, AIS/pattern A HPVA showed deceptive well-differentiated glands, often with adenofibroma-like appearance. Conversely, pattern C HPVAs consistently showed overt infiltrative features in the ovary. Sequencing confirmed the genetic relationship between primary and metastatic tumours in each case. PIK3CA alterations were identified in three of four AIS/pattern A HPVAs and three of eight pattern B/C tumours with sequenced metastases. Pattern C tumours showed a notably higher number of CNA in primary tumours compared to pattern A/B tumours. Only one metastatic AIS/pattern A HPVA had a novel pathogenic variant compared to the primary. Conversely, five of eight pattern B/C tumours with sequenced metastases developed novel pathogenic variants in the metastasis not seen in the primary. All four AIS/pattern A patients were alive and free of disease at 31, 47, 58 and 212 months after initial diagnosis. Conversely, cancer-related death was documented in five of nine pattern B/C patients with follow-up at 7, 20, 20, 43 and 87 months. CONCLUSION: Morphologically and genomically, AIS/pattern A HPVA with secondary ovarian involvement appears distinct from destructively invasive tumours. In at least a subset of these cases, ovarian spread appears to occur via trans-Mullerian superficial extension, different from the stromal and lymphatic vascular spread typical of more aggressive tumours (pattern C). These differences may explain the indolent outcome observed in the rare subset of patients with AIS/pattern A HPVA and ovarian metastasis. Our data underscore the potential for conservative surgical management approaches to pattern A HPVA.

Analysis of related factors for pathological upgrading of cervical biopsy from CIN3 to cancer after conical resection.

BACKGROUND: To investigate related factors for postoperative pathological upgrading of cervical biopsy to cervical cancer (CC) in patients with cervical intraepithelial neoplasia (CIN)3 after conical resection. METHODS: This retrospective study collected data from patients diagnosed with CIN3 by cervical biopsies at the author's Hospital between January 2012 and December 2022. The primary outcome was the pathological results of patients after conical resection. The pathological findings were categorized into the pathological upgrading group if postoperative pathology indicated CC, while those with normal, inflammatory, or cervical precancerous lesions were classified into the pathological non-upgrading group. The factors associated with upgrading were identified using multivariable logistic regression analysis. RESULTS: Among 511 patients, there were 125 patients in the pathological upgrading group (24.46%). The patients in the upgrading group were younger (47.68 ± 9.46 vs. 52.11 ± 7.02, P < 0.001), showed a lower proportion of menopausal women (38.40% vs. 53.02%, P = 0.0111), a lower proportion of HSIL (40.00% vs. 57.77%, P = 0.001), a higher rate of HPV-16/18 positive (25.60% vs. 17.36%, P = 0.011), a higher rate of contact bleeding (54.40% vs. 21.50%, P < 0.001), lower HDL levels (1.31 ± 0.29 vs. 1.37 ± 0.34 mmol/L, P = 0.002), higher neutrophil counts (median, 3.50 vs. 3.10 × 109/L, P = 0.001), higher red blood cell counts (4.01 ± 0.43 vs. 3.97 ± 0.47 × 1012/L, P = 0.002), higher platelet counts (204.84 ± 61.24 vs. 187.06 ± 73.66 × 109/L, P = 0.012), and a smaller platelet volume (median, 11.50 vs. 11.90 fL, P = 0.002).The multivariable logistic regression analysis showed that age (OR = 0.90, 95% CI: 0.86-0.94, P < 0.001), menopausal (OR = 2.68, 95% CI: 1.38-5.22, P = 0.004), contact bleeding (OR = 4.80, 95% CI: 2.91-7.91, P < 0.001), and mean platelet volume (OR = 0.83, 95% CI: 0.69-0.99, P = 0.038) were independently associated with pathological upgrading from CIN3 to CC after conical resection. CONCLUSION: Age, menopausal, contact bleeding, and mean platelet volume are risk factors of pathological upgrading from CIN3 to CC after conical resection, which could help identify high risk and susceptible patients of pathological upgrading to CC.

Upregulation of SOX9 promotes the self-renewal and tumorigenicity of cervical cancer through activating the Wnt/ß-catenin signaling pathway.

Sry-box9 (SOX9) maintains stem cell properties and plays crucial roles in many cancers. However, whether SOX9 is correlated with cervical cancer cell stemness and its detailed mechanism remains obscure. We studied the relationship between SOX9 and prognosis of cervical cancer through public database, and SOX9 was related to poor prognosis of cervical cancer. Elevated SOX9 expression enhanced the self-renewal properties and promotes tumorigenicity in cervical cancer. Overexpression of SOX9 could promote the expression of stem cell-related factors in cervical cancer cells and xenografts. Meanwhile, overexpression of SOX9 could also enhance the expressions of FZD10, ß-catenin, and c-Myc in cervical cancer cells and xenografts, while inhibiting the expression of DDK1. The activation of Wnt pathway by chir-99 021 raised the tumor spheroid ability of SOX9 knockdown HeLa cells. In addition, SOX9 could transcriptional inhibit DKK1 and activate FZD10 and MYC by binding to their promoters to affect the Wnt/ß-catenin pathway. These results demonstrated SOX9 regulated the self-renewal and tumorigenicity of cervical cancer through Wnt/ß-catenin pathway by directly transcriptional activation of FZD10, MYC and transcriptional inhibition of DKK1.

Circular RNAs and cervical cancer: friends or foes? A landscape on circRNA-mediated regulation of key signaling pathways involved in the onset and progression of HPV-related cervical neoplasms.

Cervical cancer (CC) is a common gynecologic malignancy, accounting for a significant proportion of women death worldwide. Human papillomavirus (HPV) infection is one of the major etiological causes leading to CC onset; however, genetic, and epigenetic factors are also responsible for disease expansion. Circular RNAs (circRNAs), which are known as a particular subset of non-coding RNA (ncRNA) superfamily, with covalently closed loop structures, have been reported to be involved in the progression of diverse diseases, especially neoplasms. In this framework, abnormally expressed circRNAs are in strong correlation with CC pathogenesis through regulating substantial signaling pathways. Also, these RNA molecules can be considered as promising biomarkers and therapeutic targets for CC diagnosis/prognosis and treatment, respectively. Herein, we first review key molecular mechanisms, including Wnt/ß-catenin, MAPK, and PI3K/Akt/mTOR signaling pathways, as well as angiogenesis and metastasis, by which circRNAs interfere with CC development. Then, diagnostic, prognostic, and therapeutic potentials of these ncRNA molecules will be highlighted in depth.

The interaction between social determinants of health and cervical cancer survival: A systematic review.

OBJECTIVE: This systematic review aimed to investigate what are the most relevant social determinants of health (SDH), how they are measured, how they interact among themselves and what is their impact on the outcomes of cervical cancer patients. METHODS: Search was performed in PubMed, Scopus, Web of Science, Embase, Cochrane, and Google Scholar databases from January 2001 to September 2022. The protocol was registered at PROSPERO (CRD42022346854). We followed the PICOS strategy: Population- Patients treated for cervical cancer in the United States; Intervention - Any SDH; Comparison- None; Outcome measures- Cancer treatment outcomes related to the survival of the patients; Types of studies- Observational studies. Two reviewers extracted the data following the PRISMA guidelines. Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies was used for risk of bias (ROB) assessment. RESULTS: Twenty-four studies were included (22 had low and 2 had moderate ROB). Most manuscripts analyzed data from public registries (83.3%) and only one SDH (54.17%). The SDH category of Neighborhood was not included in any study. Although the SDH were measured differently across the studies, not being married, receiving treatment at a low-volume hospital, and having public insurance (Medicaid or Medicare) or not being insured was associated with shorter survival of cervical cancer patients in most studies. CONCLUSIONS: There is a deficit in the number of studies comprehensively assessing the impact of SDH on cervical cancer treatment-related outcomes. Marital status, hospital volume and health insurance status are potential predictors of worse outcome.

Factors affecting cervical screening using the health belief model during the last decade: A systematic review and meta-analysis.

AIMS: To examine the utility of the health belief model (HBM) and other socioeconomic factors in shaping cervical screening behaviors. Also, to provide recommendations on improving screening uptake. METHODOLOGY: A systematic literature search was conducted using the PubMed/MEDLINE, Cochrane/CENTRAL, and Web of Science databases for articles reporting on the factors associated with cervical screening using the HBM within the period from January of 2002 to January of 2023. Effect sizes for the various HBM constructs were pre-determined using the log odds ratio (logOR) and expressed with their confidence intervals. All reporting was in line with the PRISMA guidelines. RESULTS: A total of 21 studies were included in the final analysis comprised of 15,365 participants. Our pooled analysis demonstrated that perceived susceptibility (OR: 1.40, 95% CI, 1.03-1.89), perceived benefits (OR: 1.30; 95% CI, 1.13-1.50), and self-efficacy (OR: 1.11; 95% CI, 1.05-1.17) were significantly associated with both the uptake of and intention to adopt preventive measures against cervical cancer. Conversely, women with higher perceptions of barriers were less likely to adopt any measure for cervical cancer screening or prevention (OR: 0.72; 95% CI, 0.57-0.91). In terms of sociodemographic effectors, older age (OR: 1.09; 95% CI, 1.01-1.19), graduate/post-graduate education (OR: 2.80; 95% CI, 1.46-5.37), higher knowledge of cervical cancer (OR: 2.21; 95% CI, 1.27-3.84), and being married (OR: 3.89; 95% CI, 1.38-10.92) were all associated with altering preventive behaviors and intentions toward cervical cancer. CONCLUSION: This review delineates the most important and effective cognitive components that should be targeted within interventions aiming to promote cervical cancer prevention.

Intratumoral and peritumoral MRI radiomics nomogram for predicting parametrial invasion in patients with early-stage cervical adenocarcinoma and adenosquamous carcinoma.

OBJECTIVE: To develop a comprehensive nomogram based on MRI intra- and peritumoral radiomics signatures and independent risk factors for predicting parametrial invasion (PMI) in patients with early-stage cervical adenocarcinoma (AC) and adenosquamous carcinoma (ASC). METHODS: A total of 460 patients with IB to IIB cervical AC and ASC who underwent preoperative MRI examination and radical trachelectomy/hysterectomy were retrospectively enrolled and divided into primary, internal validation, and external validation cohorts. The original (Ori) and wavelet (Wav)-transform features were extracted from the volumetric region of interest of the tumour (ROI-T) and 3mm- and 5mm-peritumoral rings (ROI-3 and ROI-5), respectively. Then the Ori and Ori-Wav feature-based radiomics signatures from the tumour (RST) and 3 mm- and 5 mm-peritumoral regions (RS3 and RS5) were independently built and their diagnostic performances were compared to select the optimal ones. Finally, the nomogram was developed by integrating optimal intra- and peritumoral signatures and clinical independent risk factors based on multivariable logistic regression analysis. RESULTS: FIGO stage, disruption of the cervical stromal ring on MRI (DCSRMR), parametrial invasion on MRI (PMIMR), and serum CA-125 were identified as independent risk factors. The nomogram constructed by integrating independent risk factors, Ori-Wav feature-based RST, and RS5 yielded AUCs of 0.874 (0.810-0.922), 0.885 (0.834-0.924), and 0.966 (0.887-0.995) for predicting PMI in the primary, internal and external validation cohorts, respectively. Furthermore, the nomogram was superior to radiomics signatures and clinical model for predicting PMI in three cohorts. CONCLUSION: The nomogram can preoperatively, accurately, and noninvasively predict PMI in patients with early-stage cervical AC and ASC. CLINICAL RELEVANCE STATEMENT: The nomogram can preoperatively, accurately, and noninvasively predict PMI and facilitate precise treatment decisions regarding chemoradiotherapy or radical hysterectomy in patients with early-stage cervical AC and ASC. KEY POINTS: The accurate preoperative prediction of PMI in early-stage cervical AC and ASC can facilitate precise treatment decisions regarding chemoradiotherapy or radical hysterectomy. The nomogram integrating independent risk factors, Ori-Wav feature-based RST, and RS5 can preoperatively, accurately, and noninvasively predict PMI in early-stage cervical AC and ASC. The nomogram was superior to radiomics signatures and clinical model for predicting PMI in early-stage cervical AC and ASC.

Association between programmed cell death ligand-1 expression in patients with cervical cancer and apparent diffusion coefficient values: a promising tool for patient´s immunotherapy selection.

OBJECTIVE: To investigate the associations between apparent diffusion coefficient (ADC) values extracted from three different region of interest (ROI) position approaches and programmed cell death ligand-1 (PD-L1) expression, and evaluate the performance of the nomogram established based on ADC values and clinicopathological parameters in predicting PD-L1 expression in cervical cancer (CC) patients. METHODS: Through retrospective recruitment, a training cohort of 683 CC patients was created, and a validation cohort of 332 CC patients was prospectively recruited. ROIs were delineated using three different methods to measure the mean ADC (ADCmean), single-section ADC (ADCss), and the minimum ADC of tumors (ADCmin). Logistic regression was employed to identify independent factors related to PD-L1 expression. A nomogram was drawn based on ADC values combined with clinicopathological features, its discrimination and calibration performances were estimated using the area under the curve (AUC) of receiver operating characteristic and calibration curve. The clinical benefits were evaluated by decision curve analysis. RESULTS: The ADCmin independently correlated with PD-L1 expression. The nomogram constructed with ADCmin and other independent clinicopathological-related factors: FIGO staging, pathological grade, parametrial invasion, and lymph node status demonstrated excellent diagnostic performance (AUC = 0.912 and 0.903, respectively), good calibration capacities, and greater net benefits compared to the clinicopathological model in both the training and validation cohorts. CONCLUSION: ADCmin independently correlated PD-L1 expression, and the nomogram established with ADCmin and clinicopathological independent prognostic factors had a strong predictive performance for PD-L1 expression, thereby serving as a promising tool for selecting cases eligible for immunotherapy. CLINICAL RELEVANCE STATEMENT: The minimum ADC can serve as a reliable imaging biomarker related to PD-L1 expression; the established nomogram combines the minimum ADC and clinicopathological factors that can assist clinical immunotherapy decisions.

Malnutrition is associated with poor survival in women receiving radiotherapy for cervical cancer.

OBJECTIVE: Cancer patients are at risk of malnutrition, which is associated with poor oncological outcomes. The aim of this study was to assess the incidence of malnutrition before, during, and after radiotherapy in locally advanced cervical cancer patients. In addition, we evaluated the impact of malnutrition on survival, and whether and when malnourished patients were referred to a dietitian. METHODS: This retrospective cohort study included cervical cancer patients who received primary or adjuvant radiotherapy with curative intent between January 2013 and January 2021. Patient and treatment characteristics, including longitudinal data on weight and dietary care, were retrieved from the electronic patient files. Malnutrition was defined by body mass index and weight loss according to the Global Leadership Initiative on Malnutrition (GLIM). Overall survival was estimated using the Kaplan-Meier method. Cox proportional hazard regression analysis was used to estimate hazard ratios for key prognostic factors. RESULTS: A total of 294 patients were included. Median follow-up was 40 months (range 7-101 months). Malnutrition occurred in 44 patients (15%) at baseline, in 132 (45%) during radiotherapy, and in 63 (21%) during follow-up. Referral to a dietician occurred in 45% of the 138 patients who were malnourished before or during radiotherapy. Malnutrition was significantly associated with worse survival after adjusting for age, performance score, diabetes, histology, International Federation of Gynecology and Obstetrics (FIGO) stage, and nodal stage. The 3 year overall survival in patients with malnutrition was 77% (95% confidence interval (CI) 70% to 85%) and without malnutrition 89% (95% CI 83% to 95%); p=0.001). Independent significant risk factors for worse overall survival were: malnutrition, age ˃52 years, adenocarcinoma, FIGO stage III/IV, and N1 disease. CONCLUSION: Malnutrition was common in cervical cancer patients treated with radiotherapy and was associated with a shorter overall survival. Further studies are needed to evaluate the effectiveness of better monitoring of malnutrition and faster and better dietary intervention on survival and quality of life.

Phase I study of ombrabulin in combination with paclitaxel and carboplatin in Japanese patients with advanced solid tumors.

OBJECTIVES: To evaluate the maximum tolerated dose/maximum administered dose, safety, pharmacokinetic, and efficacy profiles of ombrabulin combined with paclitaxel and carboplatin in Japanese patients with solid tumors. METHODS: Ombrabulin (25, 30, or 35 mg/m2) combined with paclitaxel (175 or 200 mg/m2) and carboplatin (AUC5 or AUC6) was administered by intravenous infusion once every 3 weeks to patients with advanced solid tumors, including cervical, ovarian, and uterine cancers. The maximum tolerated dose/maximum administered dose was defined based on the dose-limiting toxicity at cycle 1. Efficacy was assessed based on Response Evaluation Criteria In Solid Tumors (RECIST). RESULTS: In total, 18 patients were recruited for this dose escalation study. One out of six patients treated with the highest doses of combination of ombrabulin (35 mg/m2), paclitaxel (200 mg/m2), and carboplatin (AUC6) presented a dose-limiting toxicity consisting of grade 3 Escherichia urinary tract infection. This dose was defined as the maximum tolerated dose of ombrabulin. The most frequent treatment-emergent adverse events were alopecia (83.3%), neutropenia and fatigue (72.2% each), decreased appetite, nausea, diarrhea, arthralgia, and myalgia (66.7% each). The grade 3-4 treatment-emergent adverse events included neutropenia (61.1%), Escherichia urinary tract infection, drug hypersensitivity, syncope, pulmonary embolism, and hydronephrosis (one patient each). In efficacy evaluation, seven patients achieved partial response or better (38.9%), including one complete response, and seven of 18 patients had stable disease (38.9%). Pharmacokinetic profiles in this Japanese study were comparable with those observed in the previous study without Japanese patients. CONCLUSIONS: Although the maximum tolerated dose/maximum administered dose of ombrabulin (35 mg/m2) with taxane-platinum combination may be tolerable in Japanese patients in the first cycle, the dosages in the repeated treatment should be carefully selected for further study. TRIAL REGISTRATION NUMBER: NCT01293630.

Accuracy of surveillance serum squamous cell carcinoma antigen for cervical cancer recurrence after definitive chemoradiation.

OBJECTIVE: Recurrence remains a significant clinical problem for patients with cervical cancer, and early detection may improve outcomes. Serum squamous cell carcinoma antigen (SCCA) is a biomarker of prognosis and response to chemoradiotherapy. We hypothesized that elevated serum SCCA during surveillance is sensitive and specific for recurrence. METHODS: Pre-treatment and follow-up serum SCCA from patients treated with definitive-intent radiotherapy were measured via enzyme-linked immunosorbent assay in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory and analyzed retrospectively. Follow-up SCCA was defined as the value closest to recurrence, or as last available for patients without recurrence. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of follow-up SCCA for recurrence was determined for the whole cohort (Cohort 1), for patients with elevated (Cohort 2), and normal pre-treatment SCCA (Cohort 3). Patterns of failure were also evaluated. RESULTS: Of 227 patients in Cohort 1, 23% experienced recurrence, and 17% died of cervical cancer. Mean follow-up SCCA was 0.9 (±2.5) for patients with no recurrence and 6.0 (±18.7) for patients with recurrence (p=0.02). Sensitivity, specificity, PPV, and NPV of follow-up SCCA for recurrence in Cohort 1 were 38.5%, 97.1%, 80%, and 84.2%, and for patients in Cohort 2 were 54.5%, 95%, 78.3%, and 86.5%, respectively. Four of 86 patients in Cohort 3 had an elevated follow-up SCCA, two of these at the time of recurrence. Elevated pre-treatment SCCA and follow-up SCCA were associated with isolated pelvic recurrence. CONCLUSIONS: Surveillance serum SCCA has high specificity and NPV for recurrence, and may be of limited utility in patients with normal pre-treatment SCCA.

Cervical cancer screening by cytology and the burden of epithelial abnormalities in low resource settings: a tertiary-center 42-year study.

BACKGROUND: Cytological screening remains a high-impact practice, particularly in low-resource settings, for preventing cervical cancer. The examination of screening practices over time and the prevalence of epithelial abnormalities have not been investigated in longitudinal studies in one of the largest countries in the Middle East and Africa. METHODS: Routine healthcare data, between March 1981 and December 2022, were extracted from the database of the Early Cancer Detection Unit in a tertiary referral university hospital in the Greater Cairo Region, Egypt. Cervical smears were obtained using a standardized technique and sent to the cytopathology laboratory for conventional cytology examination by expert pathologists. The anonymous data were analyzed to determine the temporal trend of the number of women screened each year and the prevalence of epithelial abnormalities. RESULTS: Data included the results of satisfactory smears from 95120 women. The mean age (SD) of the women at the time of screening was 38.5 (10.5). None of the included women received an HPV vaccine. Abnormal epithelial cells were reported in 5174 women (5.44%). Of these epithelial abnormalities, the majority were low-grade squamous intraepithelial lesions in 4144 women (4.36%). Other abnormalities included atypical squamous cells in 378 women (0.40%), high-grade squamous intraepithelial lesions in 226 women (0.24%), atypical glandular cells not otherwise specified in 184 women (0.19%), adenocarcinoma in 165 women (0.17%), squamous cell carcinoma in 70 women (0.07%), and atypical glandular cells favoring neoplasms in 7 women (0.01%). Women who were at an early age at first intercourse, those who opted for routine cervical cytology screening, and those who were older at screening were more likely to have epithelial abnormalities. The yearly number of screened women was positively associated with the detection of low-grade squamous intraepithelial lesions (correlation coefficient [95% CI] = 0.84 [0.72, 0.91]) and negatively associated with the detection of squamous cell carcinoma (correlation coefficient [95% CI] = -0.55 [-0.73, -0.29]). CONCLUSIONS: The small number of annually screened Egyptian women and the temporal trend in epithelial abnormalities critically demonstrate the need for establishing and scaling up a structured population-based program to achieve the goal of eliminating cervical cancer.

Multiparametric mri-based radiomics nomogram for predicting lymph-vascular space invasion in cervical cancer.

PURPOSE: To develop and validate a multiparametric magnetic resonance imaging (mpMRI)-based radiomics model for predicting lymph-vascular space invasion (LVSI) of cervical cancer (CC). METHODS: The data of 177 CC patients were retrospectively collected and randomly divided into the training cohort (n=123) and testing cohort (n = 54). All patients received preoperative MRI. Feature selection and radiomics model construction were performed using max-relevance and min-redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) on the training cohort. The models were established based on the extracted features. The optimal model was selected and combined with clinical independent risk factors to establish the radiomics fusion model and the nomogram. The diagnostic performance of the model was assessed by the area under the curve. RESULTS: Feature selection extracted the thirteen most important features for model construction. These radiomics features and one clinical characteristic were selected showed favorable discrimination between LVSI and non-LVSI groups. The AUCs of the radiomics nomogram and the mpMRI radiomics model were 0.838 and 0.835 in the training cohort, and 0.837 and 0.817 in the testing cohort. CONCLUSION: The nomogram model based on mpMRI radiomics has high diagnostic performance for preoperative prediction of LVSI in patients with CC.

Trends in cervical cancer screening in Norway 2012-2017: a comparison study of non-immigrant and immigrant women.

AIMS: Immigrant women in Norway have lower cervical cancer screening participation than non-immigrant women. Our aim in this study was to assess whether the observed increase in screening participation during 2012-2017 was different between Norwegian-born women and immigrant women. METHODS: Data were collected from three national registries. The study included 1,409,561 women, categorized according to country of birth and immigrant background: (i) Norway, Norwegian parents; (ii) Norway, immigrant parent(s); (iii) Europe, excluding Norway; (iv) Africa; (v) Asia, including Turkey; and (vi) other countries. Trends and differences between groups were analyzed using Poisson regression analyses with adjustments for variables other studies have found to influence screening participation. Trends were assessed by including half-years as a continuous variable in the models and reported as prevalence ratios with 95% confidence intervals. RESULTS: Screening participation increased in all groups, but was not statistically significant among women from Africa in the adjusted model. The highest increase was among Norwegian women, with a 2.2% increase per year. Interaction tests showed significantly smaller increases in screening among women born in Europe (p interaction < 0.0001), Africa (p interaction < 0.0001), Asia (p interaction < 0.0001), and countries in the "Other" category (p interaction = 0.004). There was also a smaller increase among Norwegian-born women with one or more immigrant parent(s), but this was not significant (p interaction = 0.178). CONCLUSIONS: The gap in screening participation and the increasing differences in trends suggest that healthcare services do not reach all women in Norway to the same extent. One should attempt to improve this while working toward further increasing screening participation for all.

Burden of cervical cancer in India: estimates of years of life lost, years lived with disability and disability adjusted life years at national and subnational levels using the National Cancer Registry Programme data.

BACKGROUND: Cervical cancer is ranked as the second most common cancer in India. This study aims to assess the cervical cancer burden at the national and subnational level in India, projecting it for the year 2025 in terms of years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs). METHODS: Twenty-eight population based cancer registries within the National Cancer Registry Programme network contributed cancer incidence and mortality data for this analysis. The DisMod-II tool, WHO lifetables, disability weights, mortality to incidence ratio, sample registration system, and census data were used to estimate the burden of cervical cancer. The projection estimates for 2025 were performed using a negative binomial regression model. RESULTS: In 2016, the cervical cancer burden in India was 223.8 DALYs per 100,000 women. The highest age-standardised DALYs were found in the northeast region (290.1 DALYs per 100,000 women) and the lowest in the eastern region (156.1 DALYs per 100,000 women). The states of Mizoram, Arunachal Pradesh, Karnataka, and Nagaland had a higher cervical cancer burden with DALYs exceeding 300 per 100,000 women. The projected cervical cancer burden for India in 2025 was estimated to be 1.5 million DALYs. CONCLUSIONS: The study has found a significant cervical cancer burden across the regions of India, providing a baseline for monitoring impact of actions. Enhancing awareness of cervical cancer, advocating for the significance of screening, and promoting HPV vaccination among adolescents, families, and communities through informative communication campaigns are essential steps in managing and ultimately eliminating cervical cancer in India.

Investigating under-reported human papillomavirus genotypes in Grenadian women through self-sampling for cervical cancer screening.

Objective: To compare the adequacy, agreement, and acceptability of Papanicolaou testing (cytology) for cervical cancer screening using self-collected samples compared to physician-collected samples in Grenada in the Caribbean. Furthermore, the study identifies the human papillomavirus (HPV) genotypes present among asymptomatic women testing positive for HPV, the etiologic cause of cervical cancer. Methods: Participants were divided into two groups and two cervical samples were collected from the women in each group: a self-collected sample and a physician-collected sample. Cervical specimens were tested for cytology and HPV. HPV genotyping was performed on positive specimens. Results: Self-collected samples were adequate and in agreement with physician-collected samples, showing no difference between the two sampling methods. Oncogenic high-risk HPV genotypes were identified in cervical samples which were positive for atypical squamous cells and low-grade squamous intraepithelial lesions. The high-risk HPV genotypes found, notably HPV 45 and 53, differed from those most commonly reported. Although the commonly reported high-risk genotypes HPV 16 and 18 were found, so were 31, 33, 35, 52, 66, 68, and 82. Conclusions: Using self-collection facilitated the discovery of unexpected HPV genotypes among asymptomatic women in Grenada. These findings add new information to the literature regarding cervical cancer and neoplasia screening and HPV genotypes in the Caribbean. This genotype information may impact surveillance of women with low-grade lesions, HPV vaccine selection, and possibly further vaccine research. Research regarding HPV in Caribbean pathology samples of cervical neoplasia and cancer is needed.

Peritumoral stroma and systemic inflammatory response in cervical cancer.

OBJECTIVE: To compare cervical stroma in advanced cervical cancer with the control group; to compare, in the pre-treatment period, hemogram parameters in patients with advanced cervical cancer with the same parameters as the control group; and to verify if there is an association of stromal markers with prognostic factors in cervical cancer. MATERIALS AND METHODS: We prospectively evaluated 16 patients diagnosed with advanced invasive cervical cancer. A control group of 22 patients was used (uterine leiomyoma). Immunohistochemistry was performed to verify the stromal immunostaining of alpha-smooth muscle actin (SMA) and fibroblast activation protein alpha (FAP). Immunostainings and hemogram parameters were compared using Fisher's exact and Mann-Whitney Test, respectively. RESULTS: Strong FAP immunostaining was more frequent in patients with cervical cancer when compared with patients with leiomyoma (P = 0.0002). Regarding SMA, strong immunostaining was also found more in the group of cancer patients compared to the control group (P < 0.00001). The neutrophil-lymphocyte ratio (NLR) values were higher in the cancer patient group compared to the control group (P = 0.0019). There was no association of the parameters studied with prognostic factors. CONCLUSIONS: Strong FAP and SMA immunostaining was found more in patients with cervical cancer when compared to the control group. NLR values were also higher in cervical cancer.

Inhibition of Wnt/ß-catenin signaling by monensin in cervical cancer.

The challenging clinical outcomes associated with advanced cervical cancer underscore the need for a novel therapeutic approach. Monensin, a polyether antibiotic, has recently emerged as a promising candidate with anti-cancer properties. In line with these ongoing efforts, our study presents compelling evidence of monensin's potent efficacy in cervical cancer. Monensin exerts a pronounced inhibitory impact on proliferation and anchorage-independent growth. Additionally, monensin significantly inhibited cervical cancer growth in vivo without causing any discernible toxicity in mice. Mechanism studies show that monensin's anti-cervical cancer activity can be attributed to its capacity to inhibit the Wnt/ß-catenin pathway, rather than inducing oxidative stress. Monensin effectively reduces both the levels and activity of ß-catenin, and we identify Akt, rather than CK1, as the key player involved in monensin-mediated Wnt/ß-catenin inhibition. Rescue studies using Wnt activator and ß-catenin-overexpressing cells confirmed that ß-catenin inhibition is the mechanism of monensin's action. As expected, cervical cancer cells exhibiting heightened Wnt/ß-catenin activity display increased sensitivity to monensin treatment. In conclusion, our findings provide pre-clinical evidence that supports further exploration of monensin's potential for repurposing in cervical cancer therapy, particularly for patients exhibiting aberrant Wnt/ß-catenin activation.