The G-Protein-Coupled Estrogen Receptor Agonist G-1 Mediates Antitumor Effects by Activating Apoptosis Pathways and Regulating Migration and Invasion in Cervical Cancer Cells.

BACKGROUND/OBJECTIVES: Estrogens and HPV are necessary for cervical cancer (CC) development. The levels of the G protein-coupled estrogen receptor (GPER) increase as CC progresses, and HPV oncoproteins promote GPER expression. The role of this receptor is controversial due to its anti- and pro-tumor effects. This study aimed to determine the effect of GPER activation, using its agonist G-1, on the transcriptome, cell migration, and invasion in SiHa cells and non-tumorigenic keratinocytes transduced with the HPV16 E6 or E7 oncogenes. METHODS: Transcriptome analysis was performed to identify G-1-enriched pathways in SiHa cells. We evaluated cell migration, invasion, and the expression of associated proteins in SiHa, HaCaT-16E6, and HaCaT-16E7 cells using various assays. RESULTS: Transcriptome analysis revealed pathways associated with proliferation/apoptosis (TNF-α signaling, UV radiation response, mitotic spindle formation, G2/M cell cycle, UPR, and IL-6/JAK/STAT), cellular metabolism (oxidative phosphorylation), and cell migration (angiogenesis, EMT, and TGF-α signaling) in SiHa cells. Key differentially expressed genes included PTGS2 (pro/antitumor), FOSL1, TNFRSF9, IL1B, DIO2, and PHLDA1 (antitumor), along with under-expressed genes with pro-tumor effects that may inhibit proliferation. Additionally, DKK1 overexpression suggested inhibition of cell migration. G-1 increased vimentin expression in SiHa cells and reduced it in HaCaT-16E6 and HaCaT-16E7 cells. However, G-1 did not affect α-SMA expression or cell migration in any of the cell lines but increased invasion in HaCaT-16E7 cells. CONCLUSIONS: GPER is a promising prognostic marker due to its ability to activate apoptosis and inhibit proliferation without promoting migration/invasion in CC cells. G-1 could potentially be a tool in the treatment of this neoplasia.

Inhibiting SNX10 induces autophagy to suppress invasion and EMT and inhibits the PI3K/AKT pathway in cervical cancer.

PURPOSE: Cervical cancer (CC) is a prevalent malignancy among women with high morbidity and poor prognosis. Sorting nexin 10 (SNX10) is a newly recognized cancer regulatory factor, while its action on CC progression remains elusive. Hence, this study studied the effect of SNX10 on CC development and investigated the mechanism. METHODS: The SNX10 level in CC and the overall survival of CC cases with different SNX10 expressions were determined by bioinformatics analysis in GEPIA. The SNX10 expression in tumor tissues and clinical significance were studied in 64 CC cases. The overall survival was assessed using Kaplan-Meier analysis. The formation of LC3 was evaluated using immunofluorescence. Cell invasion was measured using the Transwell assay. Epithelial-to-mesenchymal transition (EMT) was determined by observing cell morphology and assessing EMT marker levels. A xenograft tumor was constructed to evaluate tumor growth. RESULTS: SNX10 was elevated in CC tissues and cells, and the CC cases with high SNX10 levels exhibited poor overall survival. Besides, SNX10 correlated with the FIGO stage, lymph node invasion, and stromal invasion of CC. SNX10 silencing induced CC cell autophagy and suppressed CC cell invasion and EMT. Meanwhile, silenced SNX10 could suppress invasion and EMT via inducing autophagy. Furthermore, SNX10 inhibition suppressed the PI3K/AKT pathway. Moreover, silenced SNX10 restrained the tumor growth, autophagy, and EMT of CC in vivo. CONCLUSION: SNX10 was enhanced in CC and correlated with poor prognosis. Silenced SNX10 induced autophagy to suppress invasion and EMT and inhibited the PI3K/AKT pathway in CC, making SNX10 a valuable molecule for CC therapy.

Time to death from cervical cancer and its predictors in hospitalized patients: a survival approach study in Mato Grosso, Brazil.

BACKGROUND: Cervical cancer (CC) is a serious public health concern, being the fourth most common cancer among women and a leading cause of cancer mortality. In Brazil, many women are diagnosed late, and in Mato Grosso, with its geographical diversity, there are specific challenges. This study analyzed hospital survival and its predictors using data from the Hospital Information System (SIH) of the Unified Health System (SUS) in Mato Grosso from 2011 to 2023. METHODS: Cox regression and Kaplan-Meier models were applied to determine survival time and identify mortality predictors. The adjusted Hazard Ratio (AHR) with a 95% Confidence Interval (CI) was used to measure the association between the factors analyzed. RESULTS: The hospital mortality rate was 9.88%. The median duration of hospitalization was 33 days (interquartile range [IQR]: 12-36), with a median survival of 43.7%. Patients were followed up for up to 70 days. In the multivariable Cox model, after adjusting for potential confounders, the risk of death during hospitalization was higher in patients aged 40-59 years (AHR = 1.39, p = 0.027) and 60-74 years (AHR = 1.54, p = 0.007), in the absence of surgical procedures (AHR = 4.48, p < 0.001), in patients with medium service complexity (AHR = 2.40, p = 0.037), and in the use of ICU (AHR = 4.97, p < 0.001). On the other hand, patients with hospital expenses above the median (152.971 USD) showed a reduced risk of death (AHR = 0.21, p < 0.001). CONCLUSION: This study highlights that hospitalized CC patients have reduced survival, underscoring the need for interventions to improve care, including strategies for early diagnosis and expanded access to adequately resourced health services.

Catalyzing Change: Assessing Inner Setting Context of Cervical Cancer Prevention Efforts in Loreto, Peru, Prior to Transition from VIA to HPV Screen-and-Treat.

Background: The objective of this study was to understand health care providers' perspectives regarding the facilitators of and barriers to the success of the former Pap and VIA-based cervical cancer program in Iquitos, Peru, using the Consolidated Framework for Implementation Research (CFIR) to inform the transition to the HPV screen-and-treat intervention. By exploring the pre-implementation organizational context, or inner setting, through the opinions of those who would implement the HPV-based intervention at the patient care level, this research lays the foundation to assess readiness before implementation and understand what's necessary to design contextually appropriate and sustainable interventions in LMIC settings. Methods: We conducted 19 semi-structured interviews with health professionals (12 nurse-midwives, 4 doctors, and 3 laboratory technicians) who administered the former Pap- and VIA-based cervical cancer EDT program. Results: Providers identified information gaps between the primary level of care, where cervical cancer screening occurs, and the hospital level of care, where diagnosis and treatment occurs. These gaps, which were caused in part by fragmented, antiquated, and overlapping data systems, resulted in the loss of patients between levels of care. Participants also noted a lack of trained personnel and basic materials. Some providers found their way around these gaps by facilitating informal information exchanges among providers to ensure women were not lost to follow-up. Conclusions: PPC relied on these findings and other data from INSPIRE Phase 1 to implement a HPV-based screen-and-treat program that dramatically increased screening and treatment; however, challenges remain regarding resources and sustainability related to HPV technology.

Quality of Life Post Cervical Cancer Treatment: A Comparison Between Radical Surgery Approach and Radiotherapy and Chemotherapy.

INTRODUCTION: The assessment of quality of life (QoL) in women with cervical cancer is crucial due to the profound changes they undergo during and after treatment. Often, the significance of sexual factors is underestimated, likely due to societal taboos surrounding such discussions. OBJECTIVE: This study aimed to determine the long-term QoL outcomes, particularly focusing on sexuality, among three therapeutic approaches for cervical cancer: chemotherapy, radiotherapy, and brachytherapy; isolated hysterectomy; and hysterectomy combined with radiotherapy. METHODS: Conducted from November 2022 to July 2023, this cross-sectional study involved 131 cervical cancer patients. Their QoL was assessed using the MDASI, FACIT-Cx, and risk factor questionnaires. Results were compared across the three treatment groups, revealing notable differences. RESULTS: Patients undergoing chemo/radio/brachytherapy showed significantly lower QoL scores compared to those undergoing isolated hysterectomy. This was evident in reduced scores across FACIT-Cx subscales for physical well-being, specific concerns, and FACIT-total (p < 0.05). The MDASI results similarly indicated greater symptoms and interference in daily activities for the chemo/radio/brachytherapy group. CONCLUSION: In conclusion, isolated hysterectomy, demonstrated superior QoL outcomes compared to chemo/radio/brachytherapy. Furthermore, the study underscored the importance of addressing sexual concerns in QoL assessments of cervical cancer survivors, emphasizing the need for comprehensive care to enhance overall well-being posttreatment.

Working towards health: A model of cervical cancer screening and treatment for factory employees in Haiti.

OBJECTIVE: In Haiti, cervical cancer continues to cause high levels of mortality and morbidity due to lack of resources and political unrest. Haitian women employed in factories are especially vulnerable because they are unable to take time away from work to access health resources. We aimed to describe a low-cost intervention which successfully addressed this need. METHODS: We present a retrospective review of data gathered through a public-private partnership, in which women working in garment factories near Port-au-Prince, Haiti, were offered health education, clinical breast exam, and free human papillomavirus (HPV) self-swab testing at their place of employment. Women testing positive for HPV were subsequently tested using visual inspection with acetic acid (VIA) to inform treatment referrals, and treated with mobile thermocoagulation in factory infirmaries. Factory-employed healthcare workers were trained on cancer screening, including VIA and clinical breast exam. RESULTS: A total of 6843 out of 6983 (98%) female factory employees attended free reproductive health education sessions, and 4005 out of 4153 eligible women (97%) were screened using HPV self-swab testing; 5176 women received a clinical breast exam. Of the women screened for HPV, 1001 (25%) tested positive and 905 (90%) of HPV-positive women received VIA testing and thermocoagulation. The intervention had a total cost of US$76 000, over half of which was spent on an HPV testing machine. CONCLUSIONS: Innovative approaches to the prevention of cervical cancer are especially necessary in very low-resource, politically unstable environments like Haiti. Self-swab and screen-and-treat programs in the workplace were acceptable to employees and factory owners. This low-cost model was reached vulnerable women through a public-private partnership, and tracked them through screening and treatment. It could be implemented elsewhere or extended to include other health services.

Cacalol Acetate as Anticancer Agent: Antiproliferative, Pro-Apoptotic, Cytostatic, and Anti-Migratory Effects.

Cacalol (C), a sesquiterpene isolated from Psacalium decompositum, has demonstrated anti-inflammatory and antioxidant activities. Its cytotoxic, antiproliferative, and pro-apoptotic effects have been previously shown in an in vitro breast cancer model. A derivative, cacalol acetate (CA), shows potential in regulating these processes, which has not been previously reported. This study focused on an in vitro cervical cancer model, assessing CA's antiproliferative, pro-apoptotic, cytostatic, and anti-migratory activities using the HeLa cell line. The natural anticancer agent indole-3-carbinol (I3C) was used as a control for comparison. CA demonstrated significant antitumor activities, including inhibiting cell growth, inducing apoptosis, arresting cells in the G2 phase of the cell cycle, and inhibiting cell migration. These effects were notably greater compared to I3C. I3C, while following a similar trend, did not induce Cas-3 expression, suggesting a different apoptotic pathway. Neither CA nor I3C increased p62 and LC3B levels, indicating they do not stimulate autophagy marker expression. Both compounds inhibited HeLa cell migration and induced cell cycle arrest. Despite both holding promise as anticancer agents for cervical cancer, CA's lower cytotoxicity and stronger regulation of tumor phenotypes make it a more promising agent compared to I3C.

Mortality due to cervical and breast cancer in health regions of Brazil: impact of public policies on cancer care.

OBJECTIVE: This analysis assessed the association between regional income, screening coverage for cervical and breast cancer, and temporal trends in mortality from these cancers in different Brazilian health regions. STUDY DESIGN: Spatiotemporal ecological study across 450 health regions of Brazil. METHODS: Data from 2010 Demographic Census were used to assess income. Variations in income distribution within health regions were measured using the Gini index. Data on screening coverage were obtained from the Ambulatory Information System (SIA/SUS). Mortality was assessed from the Global Burden of Disease Study 2019 data. The average annual percentage change (AAPC) in cervical and breast cancer mortality rates, 2010-2018, was calculated by health regions. Results were presented in regional maps. The associations between income, screening coverage and mortality changes were estimated by bivariate spatial correlation. RESULTS: Health regions located in the South and Southeast regions of Brazil had the greatest percentages of screening coverage and highest per capita incomes with the lowest Gini index values. From 2010 to 2018, mortality rates for cervical cancer were highest in the North and Northeast health regions. Breast cancer mortality rates were highest in the South and Southeast health regions. The AAPC in breast and cervical cancer mortality had a negative association with per capita income and screening coverage, and a positive association with the Gini index. CONCLUSIONS: There are large regional variations in income, screening coverage, and mortality rates for women with breast and cervical cancer. These inequities could be mitigated by policies to address income disparities and improved access to screening.

Impact of Indocyanine Green Dose on Sentinel Lymph Node Mapping in Cervical Cancer: A Systematic Review.

Over the past decade, SLN mapping has become increasingly important in cervical cancer surgery. ICG is the most commonly used tracer due to its high bilateral detection rates, ease of use, and safety. However, there is no consensus on the optimal ICG dose, leading to variability in outcomes. This systematic review aims to evaluate the impact of different ICG doses on SLN detection in early-stage cervical cancer, identifying the most effective and safe dose for clinical practice. A comprehensive search was conducted in MEDLINE/PubMed up to May 2024. Studies included assessed SLN mapping using ICG in stage IA2-IIA/IIB cervical cancer. Exclusions were applied to studies not reporting ICG dose or using multiple tracers without dose-specific results. Twelve studies were included, with ICG concentrations ranging from 0.25 mg/mL to 25 mg/mL and injection volumes from 1 to 10 mL. Overall SLN detection rates ranged from 88% to 100%, while bilateral detection rates varied between 74.1% and 98.5%. The most consistent results were obtained with an ICG concentration of 1.25 mg/mL and a 4 mL injection volume. In conclusion, an ICG concentration of 1.25 mg/mL with a 4 mL injection volume is recommended for effective SLN mapping in cervical cancer, achieving high detection rates with minimal variability. Standardizing this dose in clinical practice is suggested to improve reproducibility and outcomes.

Breast cancer and cervical cancer: a comparison of the period before and during the COVID-19 pandemic.

BACKGROUND: The coronavirus 2019 (COVID-19) pandemic impacted cancer health care in several countries, with delays in the detection and treatment of breast and cervical cancer. The objective of this study is to analyze and compare the screening, diagnosis and treatment of breast and cervical cancer in the pre-COVID period and during the COVID-19 period. METHODS: Cross-sectional study with secondary data collected from the Mortality Information System (SIM), Hospital Information System (SIH), Ambulatory Information System (SIA) and the Oncology Panel (PO) of breast cancer notifications with ICD C50.0 to C50.9 and cervix ICD C53.0 to C53.9, The analyzed period before the pandemic was from March 1 to October 1, 2019, and during the pandemic from March 1 to October 1, 2020. The period from 2013 to 2022 was also analyzed with the same information, including the number of diagnoses, treatments, and deaths from breast cancer and cervical cancer. The study population consisted of Brazilian women aged 25 to 70 years. In order to compare categorical variables between periods, the Chi-Square or Fisher's Exact tests, and Mann-Whitney U tests were applied, and the Poisson Regression model was applied to model the number of reported cases of COVID-19 and the amount of procedures. RESULTS: There was a decrease in the number of mammograms and cytopathological exams during COVID-19, as well as a decrease in cases of breast and cervical cancer. The Poisson regression showed that the increase in the number of COVID-19 cases caused a decrease in the number of breast cytopathological examinations, cervical-vaginal cytopathological examinations/microflora and screening, diagnosis, initiation of treatment for breast cancer and deaths from this disease. Meanwhile, in some regions of Brazil, as the number of Covid-19 increased, there was a significantly increase in the number of mammograms performed and cervical cancer diagnoses. CONCLUSIONS: The COVID-19 period in 2020 significantly impacted screening, diagnosis, treatment for breast and cervical cancer.

Unrevealing Lithium Repositioning in the Hallmarks of Cancer: Effects of Lithium Salts (LiCl and Li2CO3) in an In Vitro Cervical Cancer Model.

Lithium, a natural element, has been employed as a mental stabilizer in psychiatric treatments; however, some reports indicate it has an anticancer effect, prompting the consideration of repurposing lithium for cancer treatment. The potential anticancer use of lithium may depend on its form (salt type) and the type of cancer cells targeted. Little is known about the effects of Li2CO3 or LiCl on cancer cells, so we focused on exploring their effects on proliferation, apoptosis, migration, and cell cycle as part of the hallmarks of cancer. Firstly, we established the IC50 values on HeLa, SiHa, and HaCaT cells with LiCl and Li2CO3 and determined by crystal violet that cell proliferation was time-dependent in the three cell lines (IC50 values for LiCl were 23.43 mM for SiHa, 23.14 mM for HeLa, and 15.10 mM for HaCaT cells, while the IC50 values for Li2CO3 were 20.57 mM for SiHa, 11.52 mM for HeLa, and 10.52 mM for HaCaT cells.) Our findings indicate that Li2CO3 and LiCl induce DNA fragmentation and caspase-independent apoptosis, as shown by TUNEL, Western Blot, and Annexin V/IP assay by flow cytometry. Also, cell cycle analysis showed that LiCl and Li2CO3 arrested the cervical cancer cells at the G1 phase. Moreover, lithium salts displayed an anti-migratory effect on the three cell lines observed by the wound-healing assay. All these findings imply the viable anticancer effect of lithium salts by targeting several of the hallmarks of cancer.

Effects of Arborvitae (Thuja plicata) Essential Oil on Cervical Cancer Cells: Insights into Molecular Mechanisms.

AIMS: This study aimed to assess the effects of AEO in an in vitro model of cell lines derived from cervical cancer-namely, HeLa and SiHa-by screening for AEO's cytotoxic properties and examining its influence on the modulation of gene expression. BACKGROUND: Cervical cancer stands as a prevalent global health concern, affecting millions of women worldwide. The current treatment modalities encompass surgery, radiation, and chemotherapy, but significant limitations and adverse effects constrain their effectiveness. Therefore, exploring novel treatments that offer enhanced efficacy and reduced side effects is imperative. Arborvitae essential oil, extracted from Thuja Plicata, has garnered attention for its antimicrobial, anti-inflammatory, immunomodulatory, and tissue-remodeling properties; however, its potential in treating cervical cancer remains uncharted. OBJECTIVE: The objective of this study was to delve into the molecular mechanisms induced by arborvitae essential oil in order to learn about its anticancer effects on cervical cancer cell lines. METHODS: The methods used in this study were assessments of cell viability using WST-1 and annexin V- propidium iodide, mRNA sequencing, and subsequent bioinformatics analysis. RESULTS: The findings unveiled a dose-dependent cytotoxic effect of arborvitae essential oil on both HeLa and SiHa cell lines. Minor effects were observed only at very low doses in the HaCaT non-tumorigenic human keratinocyte cells. RNA-Seq bioinformatics analysis revealed the regulatory impact of arborvitae essential oil on genes enriched in the following pathways: proteasome, adherens junctions, nucleocytoplasmic transport, cell cycle, proteoglycans in cancer, protein processing in the endoplasmic reticulum, ribosome, spliceosome, mitophagy, cellular senescence, and viral carcinogenesis, among others, in both cell lines. It is worth noting that the ribosome and spliceosome KEGG pathways are the most significantly enriched pathways in HeLa and SiHa cells. CONCLUSION: Arborvitae essential oil shows potential as a cytotoxic and antiproliferative agent against cervical cancer cells, exerting its cytotoxic properties by regulating many KEGG pathways.

Pharmacokinetics and pharmacodynamics of angiogenesis inhibitors used to treat cervical cancer: current and future.

INTRODUCTION: The treatment of advanced cervical cancer is continuously developing. There is a critical need to explore new treatment options to improve cure rates and make treatment more affordable. Despite efforts in prevention, cervical cancer remains the fourth most common cancer worldwide in terms of both incidence and mortality. AREAS COVERED: This article offers an updated and critical analysis of angiogenesis inhibitors used in the treatment of advanced cervical cancer. It should be noted that this is not a systematic review. EXPERT OPINION: Bevacizumab is currently the primary antiangiogenic agent used alongside chemotherapy and has become the standard of care for advanced cervical cancer. However, there are still uncertainties regarding the molecular mechanisms and associations in cervical cancer that could help in optimizing the use of Bevacizumab. Factors such as cost, toxicity, and methodological issues in the GOG-240 trial must be considered.

Changes in the molecular nodes of the Notch and NRF2 pathways in cervical cancer tissues from the precursor stages to invasive carcinoma.

Cancer is a multifactorial disease characterized by the loss of control in the expression of genes known as cancer driver genes. Cancer driver genes trigger uncontrolled cell replication, which leads to the development of malignant tumors. A cluster of signal transduction pathways that contain cancer driver genes involved in cellular processes, such as cell proliferation, differentiation, apoptosis and dysregulated organ growth, are associated with cancer initiation and progression. In the present study, three signal transduction pathways involved in cervical cancer (CC) development were analyzed: The Hippo pathway (FAT atypical cadherin, yes-associated protein 1, SMAD4 and TEA domain family member 2), the Notch pathway [cellular-MYC, cAMP response element-binding binding protein (CREBBP), E1A-associated cellular p300 transcriptional co-activator protein and F-Box and WD repeat domain containing 7] and the nuclear factor erythroid 2-related factor 2 (NRF2) pathway [NRF2, kelch-like ECH-associated protein 1 (KEAP1), AKT and PIK3-catalytic subunit α]. Tumor samples from patients diagnosed with various stages of CC, including cervical intraepithelial neoplasia (CIN) 1, CIN 2, CIN 3, in situ CC and invasive CC, were analyzed. The mRNA expression levels were analyzed using reverse transcription-quantitative PCR assays, whereas protein expression levels were assessed through immunohistochemical tissue microarrays. High mRNA expression levels of c-MYC and AKT and low expression levels of NRF2 and KEAP1 were associated with a decreased survival time of patients with CC. Additionally, increased expression levels of c-MYC were detected in the invasive CC stage. At the protein level, increased NRF2 expression levels were observed in all five stages of CC samples compared with those in the cancer-free control samples. AKT1 was found to be dysregulated in the CIN 1 and CIN 2 stages, PI3K in the in situ and invasive stages, and CREBBP in the CIN 3 and in situ stages. In summary, the present study demonstrated significant changes in proteins of the Notch and NRF2 pathways in CC. NRF2 was overexpressed in all cervical cancer stages (cervical intraepithelial neoplasia, in situ CC and invasive CC). The present study makes an important contribution to the possible biomarker proteins to be analyzed for the presence of premalignant and malignant lesions in the cervix.

Inspección visual con ácido acético y el control del cáncer de cuello uterino en atención primaria / Visual inspection with acetic acid and the control of cervical cancer in primary care

Resumen Introducción : La inspección visual con ácido acé tico (IVAA) es una alternativa primaria para mer mar la incidencia y mortalidad por cáncer de cuello uterino (CaCu). El objetivo del estudio es conocer la proporción de mujeres de 30 a 49 años que usaron el test de IVAA en los últimos dos años y los factores asociados con el uso de la prueba, en el ámbito de la atención primaria. Métodos : Estudio transversal y multicéntrico, partici paron 706 mujeres de 30 a 49 años, usuarias de centros de atención primaria en una región del Perú. La variable dependiente fue el uso del test de IVAA, en los últimos dos años y las independientes los factores sociodemo gráficos, sociosanitarios, de información y actitud. Resultados : La proporción de mujeres que usaron el test de IVAA, fue del 30.6%. Se asociaron con mayor uso de la prueba, el área de residencia urbana, haber recibido recomendación para realizarse la IVAA, sentir preocupación por adquirir CaCu, haber oído hablar del CaCu y del virus del papiloma humano, el considerar tener mayor o igual probabilidad de desarrollar CaCu respecto a mujeres de su edad y con menor uso de la prueba, el proceder de la sierra y considerar riesgoso realizarse la IVAA. Conclusión : El programa de tamizaje del CaCu, me diante IVAA no estaría logrando el impacto deseado. Se requiere fortalecer estrategias e intervenciones en atención primaria, para mejorar las conductas y tasas del cribado.

Abstract Introduction : Visual inspection with acetic acid (VIA) is a primary alternative to reduce cervical cancer (CaCu) incidence and mortality. The study aimed to determine the proportion of women aged 30-49 years who used VIA in the last two years and the factors associated with the use of the test in the primary care setting. Methods : Cross-sectional, multicenter study. Seven hundred and six women aged 30 to 49 years partici pated, users of primary health care centers in a region of Peru. The dependent variable was the use of the VIA test in the last two years and the independent variables were sociodemographic, socio-health, information and attitudinal factors. Results : The proportion of women who used the VIA test was 30.6%. The following factors were associated with greater use of the test: urban area of residence, having received a recommendation for VIA, feeling worried about acquiring CaCu, having heard about CaCu and the human papilloma virus. Also, considering having a greater or equal probability of developing CaCu compared to women of the same age, and with lower use of the test, coming from the highlands and considering it risky to undergo VIA. Conclusion : The VIA screening program for CaCu would not be achieving the desired impact. There is a need to strengthen strategies and interventions in primary care to improve screening behaviors and rates.

Uncovering the Expression Pattern of the Costimulatory Receptors ICOS, 4-1BB, and OX-40 in Exhausted Peripheral and Tumor-Infiltrating Natural Killer Cells from Patients with Cervical Cancer.

Cervical cancer (CC) poses a significant health burden, particularly in low- and middle-income countries. NK cells play a crucial role against CC; however, they can become exhausted and lose their cytotoxic capacity. This work explores the expression of costimulatory receptors (ICOS, 4-1BB, OX-40) in exhausted NK cells from CC patients. Peripheral blood and tumor biopsies were collected, and flow cytometry was used to evaluate the expression of costimulatory receptors in exhausted NK cells. There is an increase of peripheral exhausted NK cells (PD-1+TIGIT+) in CC patients; this subpopulation has a selectively increased expression of the costimulatory receptors ICOS and 4-1BB. An exhausted population is also highly increased in tumor-infiltrating NK cells, and it shows a dramatically increased expression of the costimulatory receptors ICOS (>15×) and 4-1BB (>10×) compared to peripheral NK cells. The exhausted cells, both in the periphery and in the tumor infiltrating lymphocytes (TILs), are also more likely than non-exhausted NK cell populations (PD-1-TIGIT-) to express these costimulatory receptors; increases ranging from 2.0× ICOS, 2.4× 4-1BB, and 2.6× OX-40 in CD56dim PBMCs to 1.5× ICOS, 5× 4-1BB, and 10× OX-40 in TILs were found. Our study demonstrates for the first time the increased expression of the costimulatory receptors ICOS, 4-1BB, and OX-40 in peripheral CD56dim, CD56bright, and tumor-infiltrating NK cells in CC. Targeting these receptors for stimulation could reverse exhaustion and be a promising immunotherapy strategy.

SEOM-GEICO Clinical Guidelines on cervical cancer (2023).

Cervical cancer (CC) is the fourth most common cancer and the fourth leading cause of mortality in women worldwide. It is strongly associated with high-risk human papillomavirus infection. High-income countries that have implemented human papillomavirus (HPV) vaccination and screening programs have seen dramatic reductions in CC incidence, while developing countries where these programs are not available continue to experience high rates of CC deaths. In early-stage CC, the primary treatment is surgery or radiotherapy, whereas concurrent chemo-radiotherapy (CRT) remains the conventional approach in locally advanced stages until the upcoming approval of immunotherapy. The incorporation of immunotherapy in combination with chemotherapy (with or without bevacizumab) in first line and as monotherapy in second line after platinum-based chemotherapy, has significantly increased overall survival (OS) in recurrent or metastatic CC. The purpose of this guideline is to summarize the most relevant evidence in the diagnosis, treatment, and follow-up of CC and to provide evidence-based recommendations for clinical practice.

Synchronous primary endometrial adenocarcinoma and primary squamous cell carcinoma of the cervix: A case report and literature review.

The synchronous occurrence of primary endometrioid endometrial adenocarcinoma and primary squamous cell carcinoma of the cervix is exceedingly rare. Ovarian and endometrial cancers represent the most frequently observed forms of synchronous gynaecological malignancies. In contrast, in less than 1 % of cases, endometrial cancer coexists with primary cervical cancer. Considering the unique characteristics of each primary malignancy, the management of synchronous tumours of the female genital tract poses significant challenges and requires a multidisciplinary, tailored approach to treatment. This report concerns the case of a 63-year-old woman who underwent radical hysterectomy, bilateral salpingo-oophorectomy and bilateral pelvic lymph node dissection following a histological diagnosis of a poorly differentiated squamous cell carcinoma on cervical biopsy. Histological assessment of the surgical specimen also confirmed a primary grade I endometrioid endometrial adenocarcinoma confined to the endometrium and grade 3 squamous cell cancer of the cervix. The patient was successfully treated with adjuvant vaginal brachytherapy after primary surgery. Synchronous endometrial adenocarcinoma and squamous cell carcinoma of the cervix is rare and associated with a poor prognosis. Fewer than ten cases could be found in the medical literature. This report raises awareness and adds to the study of an unusual synchronous cancer of the female genital tract and contributes evidence to advance the development of standardized treatment protocols.