Sociodemographics, behaviour and knowledge of first South African HPV-vaccine recipients.

BACKGROUND:  Infection with the human papillomavirus (HPV) is a necessary cause of cervical cancer and is one of the most prevalent sexually transmitted infections worldwide. Primary prevention strategies target reducing HPV acquisition through vaccination, limiting exposure (e.g. delayed sexual debut, barrier contraception) and health education focusing on sexual behaviour and tobacco use. METHODS:  The ImmunoVACCS study, conducted from 2019 to 2022 in two provinces in South Africa, examined sociodemographic characteristics, sexual practices, and knowledge of cervical cancer and the HPV vaccine among young female vaccine recipients. It encompassed participants from the previously conducted vaccine implementation trials, VACCS 1 and VACCS 2 (2011-2014). Recruitment involved telephonic contact with eligible potential participants. Data were collected through self-administered questionnaires. RESULTS:  One hundred and eleven participants took part in the current study (median age: 20 years; age range: 16-22 years). Most sexually active participants had their first engagement in secondary school (96.2%), and 77.2% used contraception during their last sexual activity. Knowledge gaps were evident, with only 13.5% recognising cervical cancer's cervix origin and 3.6% attributing it to a virus. Despite this, 70.3% had heard of a vaccine for cervical cancer. Less than half knew about the importance of regular Pap smears (49.5%), vaccine protection (44.1%) or condom use (20.7%) against HPV and cervical cancer. CONCLUSION:  The current study demonstrates that young women still lack complete information on cervical cancer and its risk factors even after receiving health education linked with vaccination.Contribution: This study underscores the necessity of ongoing education about HPV, its risks and preventive measures among young women to combat cervical cancer.

EPAS1, a hypoxia- and ferroptosis-related gene, promotes malignant behaviour of cervical cancer by ceRNA and super-enhancer.

Hypoxia and Ferroptosis are associated with the malignant behaviour of cervical cancer. Endothelial PAS domain-containing protein 1 (EPAS1) contributes to the progression of cervical cancer. EPAS1 plays important roles in hypoxia and ferroptosis. Using the GEO dataset, machine-learning algorithms were used to screen for hypoxia- and ferroptosis-related genes (HFRGs) in cervical cancer. EPAS1 was identified as the hub gene. qPCR and WB were used to investigate the expression of EPAS1 in normal and cervical cancer tissues. The proliferation, invasion and migration of EPAS1 cells in HeLa and SiHa cell lines were detected using CCK8, transwell and wound healing assays, respectively. Apoptosis was detected by flow cytometry. A dual-luciferase assay was used to analyse the MALAT1-miR-182-5P-EPAS1 mRNA axis and core promoter elements of the super-enhancer. EPAS1 was significantly overexpressed in cervical cancer tissues. EPAS1 could increase the proliferation, invasion, migration of HeLa and SiHa cells and reduce the apoptosis of HeLa and SiHa cell. According to the double-luciferase assay, EPAS1 expression was regulated by the MALAT1-Mir-182-5p-EPAS1 mRNA axis. EPAS1 is associated with super-enhancers. Double-luciferase assay showed that the core elements of the super-enhancer were E1 and E3. EPAS1, an HFRG, is significantly overexpressed in cervical cancer. EPAS1 promotes malignant behaviour of cervical cancer cells. EPAS1 expression is regulated by super-enhancers and the MALAT1-miR-182-5P- EPAS1 mRNA axis. EPAS1 may be a target for the diagnosis and treatment of cervical cancer.

Prognostic analysis of stage IIIC1p cervical cancer patients.

Background: Stage IIIC1p cervical cancer is characterized by marked heterogeneity and considerable variability in the postoperative prognosis. This study aimed to identify the clinical and pathological characteristics affecting the survival of patients diagnosed with stage IIIC1p cervical cancer. Methods: We retrospectively analyzed patients diagnosed with stage IIIC1p cervical cancer who underwent radical hysterectomy and lymph node dissection between March 2012 and March 2022. Overall survival (OS) was estimated using Kaplan-Meier survival curves. Univariate and multivariate Cox proportional hazards models were used to evaluate prognostic factors for OS and forest plots were used to visualize these findings. Nomogram charts were created to forecast survival rates at 3 and 5 years, and the accuracy of predictions was evaluated using Harrell's concordance index (C-index) and calibration curves. Results: The study cohort comprised 186 women diagnosed with stage IIIC1p cervical cancer. The median follow-up duration was 51.1 months (range, 30-91 months), and the estimated 5-year OS rate was 71.5%. Multivariate analysis revealed that concurrent chemoradiotherapy plus adjuvant chemotherapy (CCRT + AC), monocyte-lymphocyte ratio (MLR), ratio of lymph node metastasis (LNM), and squamous cell carcinoma antigen (SCCA) levels independently predicted OS. Conclusions: Significant prognostic disparities exist among patients diagnosed with stage IIIC1p cervical cancer. MLR, ratio of LNM, and SCCA were associated with poor OS. In contrast, the CCRT + AC treatment regimen appeared to confer a survival advantage.

Trends in the Prevalence and Mortality of Cervical Cancer in the Kyrgyz Republic.

BACKGROUND: Cervical cancer represents a significant health concern globally and is the fourth most common cancer among women, leading to substantial morbidity and mortality. The primary cause is persistent infection with high-risk human papillomavirus (HPV) types. Despite advancements in prevention, screening, diagnosis, and treatment, disparities in cervical cancer outcomes persist due to variations in screening accessibility and socioeconomic factors. This study focuses on women in the Kyrgyz Republic, highlighting regional disparities and the critical role of early detection. METHODS: A retrospective data analysis was conducted on 1,338 women diagnosed with cervical cancer from 2012 to 2017 in the Kyrgyz Republic. Data were sourced from national health centers, focusing on sociodemographic metrics, clinical staging, and regional distributions. The study utilized statistical analysis to evaluate prevalence and mortality rates, employing the analysis of variance for comparison, significance, and analyzing trends over time. RESULTS: The prevalence of cervical cancer in the Kyrgyz Republic increased from 97.5 per 100,000 females in 2012 to 105.3 per 100,000 in 2017, with mortality rates of 8.3-9.7%. Notably, regional disparities were evident, with Chui, Osh, Jalal-Abad, and Bishkek experiencing increased prevalence rates, while Talas, Issyk-Kul, Naryn, and Batken reported decreased prevalence. Screening programs, particularly the introduction of Pap smears, have been effective in reducing both prevalence and mortality rates in areas with broad population coverage. However, the study highlighted significant variations in outcomes across different regions, underscoring the importance of targeted prevention and screening efforts. CONCLUSIONS: The study confirms the ongoing challenge of cervical cancer in the Kyrgyz Republic, emphasizing the need for improved screening and prevention strategies to address disparities in outcomes. The introduction of pilot screening programs represents a crucial step forward. However, the findings also point to the necessity for enhanced oncological literacy among primary care physicians and the implementation of comprehensive strategies to overcome socioeconomic and regional barriers to effective cervical cancer prevention and treatment. The reduction in prevalence observed in 2016 suggests progress, highlighting the potential impact of focused prevention and screening initiatives.

Circular RNA circIL21R promotes cervical cancer cells proliferation and migration by sponging the miR-1205/PTBP1 axis.

Increasing research has shown that the abnormal expression of circRNAs is closely related to tumorigenesis, apoptosis, and patient prognosis in cervical cancer. This study aimed to reveal the procancer role of circIL21R in cervical cancer and investigate its related molecular mechanisms. Bioinformatics analysis revealed that circIL21R promotes the progression of cervical cancer via the miR-1205/PTBP1 axis. CircIL21R expression was significantly greater in tumor tissue than in adjacent normal tissue, and higher circIL21R expression indicated shorter survival. We applied MTS assays, EdU assays, and Transwell assays to show that the overexpression of circIL21R promoted cervical cancer cell proliferation and invasion. Mechanistically, circIL21R promoted the expression of PTBP1 by sponging miR-1205. Moreover, rescue assays confirmed that regulating the expression of miR-1205 or PTBP1 could reverse the tumorigenic effect caused by circIL21R overexpression. In addition, circIL21R promoted the tumorigenesis of cervical cancer in vivo. In summary, our study demonstrated that circIL21R was highly expressed in cervical cancer and upregulated PTBP1 expression by acting as a ceRNA for miR-1205, making outstanding contributions to several malignant biological processes in cervical cancers, such as growth, proliferation, and invasion. CircIL21R is a potential biomarker for the diagnosis and treatment of cervical cancer.

Clinical analysis of 314 patients with high-grade squamous intraepithelial lesion who underwent total hysterectomy directly: a multi-center, retrospective cohort study.

OBJECTIVE: To identify the risk factors of cervical high-grade squamous intraepithelial lesion(HSIL) complicated with occult cervical cancer and standardize the management of initial treatment for HSIL. METHOD: The clinical data of patients who underwent total hysterectomy directly due to HSIL in the obstetrics and gynecology department of two tertiary hospitals and three secondary hospitals from 2018 to 2023 were collected. Their general characteristics, pathological parameters and survival status were analyzed. Logistic regression model was used to analyze the correlation between clinical parameters and postoperative pathological upgrading. RESULT: 1. Among the 314 patients with HSIL who underwent total hysterectomy directly, 73.2% were from primary hospitals. 2. 25 patients (7.9%) were pathologically upgraded to cervical cancer, all of which were early invasive cancer. 3. Up to now, there was no recurrence or death in the 25 patients with early-stage invasive cancer, and the median follow-up period was 21 months(range 2-59 months). 4. Glandular involvement(OR 3.968; 95%CI 1.244-12.662) and lesion range ≥ 3 quadrants (OR 6.527; 95% CI 1.78-23.931), HPV 16/18 infection (OR 5.382; 95%CI 1.947-14.872), TCT ≥ ASC-H (OR 4.719; 95%CI 1.892-11.766) were independent risk factors that affected the upgrading of postoperative pathology. 5. The area under the curve (AUC) calculated by the Logistic regression model was 0.840, indicating that the predictive value was good. CONCLUSION: There is a risk of occult cervical cancer in patients with HSIL. Glandular involvement, Lesion range ≥ 3 quadrants, HPV 16/18 infection and TCT ≥ ASC-H are independent risk factors for HSIL combined with occult cervical cancer. The prognosis of biopsy-proved HSIL patients who underwent extrafascial hysterectomy and unexpected early invasive cancer was later identified on specimen may be good.

The performance of single and combination test strategies using visual inspection, cytology, high-risk HPV DNA and HPV16/18 to screen South African women with and without HIV-infection.

BACKGROUND: Cervical cancer screening strategies should ideally be informed by population-specific data. Strategies recommended for secondary prevention, are often inadequately studied in populations with high cervical disease burdens. This report describes the test performance measured against CIN2 + /CIN3 + histology in HIV-positive women (HPW) and HIV-negative women (HNW) with the aim to determine the most effective strategies to identify South African women at risk. METHODS: Primary screening using visual inspection, cytology and HPV DNA (cobas®) was performed in two South African provinces on 456 HPW and 639 HNW participating in the multicentric DiaVACCS trial. Histology was obtained for 91.7% screen-positive and 42.7% screen-negative participants, and unavailable histology was determined by multiple imputation to adjust for verification bias. Cross-sectional test performance was calculated for single and combination test strategies with and without intermediate risk categories using different cut-offs. Minimum acceptability for sensitivity and specificity, treatment and follow-up numbers were considered to evaluate strategies. RESULTS: The only single test to reach acceptability in HPW was cytology (LSIL) [sensitivity 71.2%; specificity 90.5%; treatment 33.4%]; in HNW only HPV (hr) qualified [sensitivity 68.2%; specificity 85.2%; treatment 23.5%]. The universally best performing strategy which also resulted in smaller treatment numbers without intermediate risk group was primary HPV(hr), with treatment of both HPV(16/18) and cytology (ASCUS +) [HPW: sensitivity 73.6%; specificity 89.7%; treatment 34.7%. HNW: sensitivity 59.1%; specificity 93.6%; treatment 13.9%]. DNA testing for hrHPV (any) and hrHPV (16/18) was the best universally acceptable strategy with an intermediate risk category (early follow-up) in HPW [sensitivity 82.1%; specificity 96.4%; treatment 17.1%; follow-up 31.4%] and HNW [sensitivity 68.2%; specificity 96.7%; treatment 7.6%; follow-up 15.9%]. In comparison, using both HPV (16/18) and cytology (ASCUS +) as secondary tests in hrHPV positive women, decreased follow-up [HPW 13.8%, HNW 9.6%], but increased treatment [HPW 34.7%, HNW 13.9%]. CONCLUSION: Using hrHPV (any) as primary and both HPV16/18 and cytology as secondary tests, was universally acceptable without an intermediate risk group. Strategies with follow-up groups improved screening performance with smaller treatment numbers, but with effective management of the intermediate risk group as prerequisite.

Serum Proteomic Signatures in Cervical Cancer: Current Status and Future Directions.

In 2020, the World Health Organization (WHO) reported 604,000 new diagnoses of cervical cancer (CC) worldwide, and over 300,000 CC-related fatalities. The vast majority of CC cases are caused by persistent human papillomavirus (HPV) infections. HPV-related CC incidence and mortality rates have declined worldwide because of increased HPV vaccination and CC screening with the Papanicolaou test (PAP test). Despite these significant improvements, developing countries face difficulty implementing these programs, while developed nations are challenged with identifying HPV-independent cases. Molecular and proteomic information obtained from blood or tumor samples have a strong potential to provide information on malignancy progression and response to therapy in CC. There is a large amount of published biomarker data related to CC available but the extensive validation required by the FDA approval for clinical use is lacking. The ability of researchers to use the big data obtained from clinical studies and to draw meaningful relationships from these data are two obstacles that must be overcome for implementation into clinical practice. We report on identified multimarker panels of serum proteomic studies in CC for the past 5 years, the potential for modern computational biology efforts, and the utilization of nationwide biobanks to bridge the gap between multivariate protein signature development and the prediction of clinically relevant CC patient outcomes.

Expression of Potential Antibody-Drug Conjugate Targets in Cervical Cancer.

(1) Background: There is a huge unmet clinical need for novel treatment strategies in advanced and recurrent cervical cancer. Several cell membrane-bound molecules are up-regulated in cancer cells as compared to normal tissue and have revived interest with the introduction of antibody-drug conjugates (ADCs). (2) Methods: In this study, we characterize the expression of 10 potential ADC targets, TROP2, mesotheline, CEACAM5, DLL3, folate receptor alpha, guanylatcyclase, glycoprotein NMB, CD56, CD70 and CD138, on the gene expression level. Of these, the three ADC targets TROP2, CEACAM5 and CD138 were further analyzed on the protein level. (3) Results: TROP2 shows expression in 98.5% (66/67) of cervical cancer samples. CEACAM5 shows a stable gene expression profile and overall, 68.7% (46/67) of cervical cancer samples are CEACAM-positive with 34.3% (23/67) of cervical cancer samples showing at least moderate or high expression. Overall, 73.1% (49/67) of cervical cancer samples are CD138-positive with 38.8% (26/67) of cervical cancer samples showing at least moderate or high expression. (4) Conclusions: TROP2, CEACAM5 or CD138 do seem suitable for further clinical research and the data presented here might be used to guide further clinical trials with ADCs in advanced and recurrent cervical cancer patients.

To who and by who: Discussions of sexual health, fertility, and premature menopause with women with locally advanced cervical cancer.

PURPOSE: To investigate whether gynecologic and radiation oncologists document discussions of chemoradiation treatment's gonadotoxicity for patients with cervical cancer and what patient and physician factors make discussions more likely. METHODS AND MATERIALS: Women with LACC treated with definitive CRT between 2009 and 2022 were included. Visit notes with gynecologic and radiation oncologists were reviewed for sexual health discussions. Fertility and premature menopause discussions were only evaluated among premenopausal patients. Variables of interest including demographics and staging were collected. Univariate and multivariate analyses were conducted using Rv4.2.1. RESULTS: A total of 93 women were included (22-91 years old). Most were Stage IIB (32%) or IIIB (34%). Sexual health discussions occurred among 74.2% of patients and did not have a significant relationship with any patient factors. Fertility discussions occurred with 17.5% of the 57 premenopausal patients and were more likely among younger patients (≤31.9, p < 0.001) with fewer children (≤1, p < 0.001). Premature menopause discussions occurred among 73.7% of premenopausal patients and were more likely among younger patients (≤39.0, p = 0.015). CONCLUSIONS: It is promising to see that oncologists are discussing sexual health and premature menopause with most patients. The limited fertility discussions suggest that oncologists are less likely to discuss fertility as women approach the age of menopause or already have children. Involvement of reproductive endocrinologists and psychologists may provide patients with a more comprehensive understanding of long-term quality of life.

Mesencephalic astrocyte-derived neurotrophic factor inhibits cervical cancer progression via regulating macrophage phenotype.

BACKGROUND: Cervical cancer is a common gynecologic malignant tumor, but the critical factors affecting cervical cancer progression are still not well demonstrated. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been widely recognized as an anti-inflammatory factor to regulate macrophage polarization. In this study, the effect and mechanism of MANF on cervical cancer were preliminarily explored. METHODS AND RESULTS: Kaplan-Meier curve was used to show the overall survival time of the involved cervical cancer patients with high and low MANF expression in cervical cancer tissues. MANF was highly expressed in peritumoral tissues of cervical carcinoma by using immunohistochemistry and western blot. MANF mRNA level was detected by using qRT-PCR. Dual-labeled immunofluorescence showed MANF was mainly expressed in macrophages of cervical peritumoral tissues. Moreover, MANF-silenced macrophages promoted HeLa and SiHa cells survival, migration, invasion and EMT via NF-κB signaling activation. The results of tumor formation in nude mice indicated MANF-silenced macrophages promoted cervical tumor formation in vivo. CONCLUSION: Our study reveals an inhibitory role of MANF in cervical cancer progression, indicating MANF as a new and valuable therapeutic target for cervical cancer treatment.

The performance of the node reporting and data system 1.0 (Node-RADS) and DWI-MRI in staging patients with cervical carcinoma according to the new FIGO classification (2018).

PURPOSE: To evaluate the diagnostic accuracy of the Node-RADS score and the utility of apparent diffusion coefficient (ADC) values in predicting metastatic lymph nodes (LNs) involvement in cervical cancer (CC) patients using magnetic resonance imaging (MRI). The applicability of the Node RADS score across three readers with different years of experience in pelvic imaging was also assessed. MATERIAL AND METHODS: Among 140 patients, 68 underwent staging MRI, neoadjuvant chemotherapy and radical surgery, forming the study cohort. Node-RADS scores of the main pelvic stations were retrospectively determined to assess LN metastatic likelihood and compared with the histological findings. Mean ADC, relative ADC (rADC), and correct ADC (cADC) values of LNs classified as Node-RADS ≥ 3 were measured and compared with histological reports, considered as gold standard. RESULTS: Sensitivity, specificity, positive and negative predictive values (PPVs and NPVs), and accuracy were calculated for different Node-RADS thresholds. Node RADS ≥ 3 showed a sensitivity of 92.8% and specificity of 72.5%. Node RADS ≥ 4 yielded a sensitivity of 71.4% and specificity of 100%, while Node RADS 5 yielded 42.9% and 100%, respectively. The diagnostic performance of mean ADC, cADC and rADC values from 78 LNs with Node-RADS score ≥ 3 was assessed, with ADC demonstrating the highest area under the curve (AUC 0.820), compared to cADC and rADC values. CONCLUSION: The Node-RADS score provides a standardized LNs assessment, enhancing diagnostic accuracy in CC patients. Its ease of use and high inter-observer concordance support its clinical utility. ADC measurement of LNs shows promise as an additional tool for optimizing patient diagnostic evaluation.

[Retracted] MicroRNA­329­3p targets MAPK1 to suppress cell proliferation, migration and invasion in cervical cancer.

Following the publication of the above article, a concerned reader drew to the Editor's attention that certain of the Transwell cell migration and invasion assay data featured in Figs. 5C and 6C were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had already been published elsewhere prior to the submission of this paper to Oncology Reports, or were submitted for consideration for publication at around the same time. In view of the fact that certain of these data had already apparently been published prior to the submission of this article for publication, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 37: 2743­2750, 2017; DOI: 10.3892/or.2017.5555].

Using electronic health records to evaluate the adherence to cervical cancer prevention guidelines: A cross-sectional study.

OBJECTIVE: The fight against cervical cancer requires effective screening together with optimal and on-time treatment along the care continuum. We examined the impact of cervical cancer testing and treatment guidelines on testing practices, and follow-up adherence to guidelines. METHODS: Data from Estonian electronic health records and healthcare provision claims for 50,702 women was used. The annual rates of PAP tests, HPV tests and colposcopies during two guideline periods (2nd version 2012-2014 vs 3rd version 2016-2019) were compared. To assess the adherence to guidelines, the subjects were classified as adherent, over- or undertested based on the timing of the appropriate follow-up test. RESULTS: The number of PAP tests decreased and HPV tests increased during the 3rd guideline period (p < 0.01). During the 3rd guideline period, among 21-29-year-old women, the adherence to guidelines ranged from 38.7% (44.4…50.1) for ASC-US to 73.4% (62.6…84.3) for HSIL and among 30-59-year-old from 49.0% (45.9…52.2) for ASC-US to 65.7% (58.8…72.7) for ASCH. The highest rate of undertested women was for ASC-US (21-29y: 25.7%; 30-59y: 21.9%). The rates of over-tested women remained below 12% for all cervical pathologies observed. There were 55.2% (95% CI 49.7…60.8) of 21-24-year-olds and 57.1% (95% CI 53.6…60.6) of 25-29-year-old women who received HPV test not adherent to guidelines. CONCLUSIONS: Our findings highlighted some shortcomings in guideline adherence, especially among women under 30. The insights gained from this study help to improve the quality of care and, thus, reduce cervical cancer incidence and mortality.

Tertiary lymphoid structures associated with enhanced anti-tumor immunity and favorable prognosis in cervical squamous carcinoma.

BACKGROUND: Cervical squamous carcinoma (CESC) is the main subtype of cervical cancer. Unfortunately, there are presently no effective treatment options for advanced and recurrent CESC. Tertiary lymphoid structures (TLSs) are clusters of lymphoid cells that resemble secondary lymphoid organs; nevertheless, there is no summary of the clinical importance of TLS in CESC. METHODS: A large set of transcriptomic and single-cell RNA-sequencing (scRNA-seq) datasets were used to analyze the pattern of TLS and its immuno-correlations in CESC. Additionally, an independent in-house cohort was collected to validate the correlation between TLS and TME features. RESULTS: In the current study, we found that the presence of TLS could predict better prognosis in CESC and was correlated with the activation of immunological signaling pathways and enrichment of immune cell subpopulations. In addition, TLS was associated with reduced proliferation activity in tumor cells, indicating the negative correlation between TLS and the degree of malignancy. Last but not least, in two independent immunotherapy cohorts, tumors with the presence of TLS were more sensitive to immunotherapy. CONCLUSION: Overall, TLS is related to an inflamed TME and identified immune-hot tumors, which could be an indicator for the identification of immunological features in CESC.

M6A-induced transcription factor IRF5 contributes to the progression of cervical cancer by upregulating PPP6C.

Cervical cancer (CC) is a gynaecological malignancy tumour that seriously threatens women's health. Recent evidence has identified that interferon regulatory factor 5 (IRF5), a nucleoplasm shuttling protein, is a pivotal transcription factor regulating the growth and metastasis of various human tumours. This study aimed to investigate the function and molecular basis of IRF5 in CC development. IRF5, protein phosphatase 6 catalytic subunit (PPP6C) and methyltransferase-like 3 (METTL3) mRNA levels were evaluated by quantitative real-time (qRT)-polymerase chain reaction (PCR). IRF5, PPP6C, METTL3, B-cell lymphoma 2 and Bax protein levels were detected using western blot. Cell proliferation, migration, invasion, angiogenesis and apoptosis were determined by using colony formation, 5-ethynyl-2'-deoxyuridine (EdU), transwell, tube formation assay and flow cytometry assay, respectively. Glucose uptake and lactate production were measured using commercial kits. Xenograft tumour assay in vivo was used to explore the role of IRF5. After JASPAR predication, binding between IRF5 and PPP6C promoter was verified using chromatin immunoprecipitation and dual-luciferase reporter assays. Moreover, the interaction between METTL3 and IRF5 was verified using methylated RNA immunoprecipitation (MeRIP). IRF5, PPP6C and METTL3 were highly expressed in CC tissues and cells. IRF5 silencing significantly inhibited cell proliferation, migration, invasion, angiogenesis and glycolytic metabolism in CC cells, while induced cell apoptosis. Furthermore, the absence of IRF5 hindered tumour growth in vivo. At the molecular level, IRF5 might bind with PPP6C to positively regulate the expression of PPP6C mRNA. Meanwhile, IRF5 was identified as a downstream target of METTL3-mediated m6A modification. METTL3-mediated m6A modification of mRNA might promote CC malignant progression by regulating PPP6C, which might provide a promising therapeutic target for CC treatment.

Effectiveness of sentinel lymph node biopsy and bilateral pelvic nodal dissection using methylene blue dye in early-stage operable cervical cancer-A prospective study.

OBJECTIVE: To evaluate the effectiveness of methylene blue dye in detecting sentinel lymph nodes (SLNs) in women with early-stage operable (defined as FIGO I-IIA) cervical cancer. It also aims to evaluate procedural challenges and accuracy. METHOD: This prospective study, which focused on 20 women with early-stage cervical cancer, was carried out between June 2016 and December 2017. These patients had SLN mapping with methylene blue dye injections and thorough examinations, including imaging. All patients underwent radical hysterectomy and complete bilateral pelvic lymphadenectomy. No additional investigation was done on the lymph node in cases where a metastasis was found in the first H&E-stained segment of the sentinel node. RESULT: 20 patients were included in the analysis. The median age of the subjects was 53, and 95 % of them had squamous cell carcinoma. 90 % of the time, the identification of SLNs was effective, and 55 SLNs were found, of which 52.7 % were on the right side of the pelvis and 47.3 % on the left. The obturator group had the most nodes, followed by the external and internal iliac groups in descending order of occurrence. Metastasis was detected in 3 patients, resulting in a sensitivity of 100 % and a specificity of 93.75 % for SLN biopsy. Notably, no false-negative SLNs were found. Complications related to methylene blue usage included urine discoloration in 30 % of patients. CONCLUSION: This trial highlights the promising efficacy and safety of methylene blue dye alone for SLN identification in early-stage operable cervical cancer, with a notably higher success rate. Despite limitations like a small sample size, healthcare professionals and researchers can build upon the insights from this study to enhance cervical cancer management.

LINC01605 promotes malignant phenotypes of cervical cancer via miR-149-3p/WNT7B axis.

BACKGROUND: Long non-coding RNAs (LncRNA) play a pivotal role in the progression of various malignancies. Despite recent identification as an oncogene associated with tumorigenesis. The precise role of LINC01605 in cervical cancer (CC) remains unclear. Therefore, the objective of this study was to investigate the influence of LINC01605 on proliferation and invasion of CC cells, while also exploring its potential underlying mechanisms. METHODS: The expression of LINC01605 in CC cell lines was analyzed using the TCGA database and qRT-PCR. Various assays, including CCK-8 and transwell analysis, were conducted on CC cells to assess the influence of LINC01605 on their proliferation, migration, and invasion capabilities. Bioinformatics and dual luciferase reporter gene assays were employed to analyze the target genes of LINC01605 and miR-149-3p. To further investigate the mechanism of action, transfection and investigation were performed using specific siRNA, miRNA mimics, or inhibitors. RESULTS: The expression of LINC01605 exhibited a significant increase in CC cell lines, and this upregulation was associated with an unfavorable prognosis. Modulating the expression of LINC01605, either by down-regulating or up-regulating it, exerted suppressive or stimulatory effects on the growth and invasion of HeLa and Siha cells. LINC01605 functioned as a competitive endogenous RNA (ceRNA) for miR-149-3p, with WNT7B being identified as a target gene of miR-149-3p. The involvement of LINC01605 in CC development is facilitated by its ability to regulate the expression of WNT7B through sequestering miR-149-3p. CONCLUSION: Our study demonstrates that LINC01605 acts as a competitive endogenous RNA in modulating the effects of WNT7B on the proliferation and invasion of CC cells by sequestering miR-149-3p. This research provides novel insights into the involvement of LINC01605 in the advancement of CC.

The efficacy of immune checkpoint inhibitors on low PD-L1 cervical cancer: A meta-analysis.

Background and Aims: The effectiveness of immune checkpoint inhibitors (ICIs) in low programmed death ligand 1 (PD-L1) expression in cervical cancer (CC) patients remains unknown. We aimed to evaluate the efficacy of ICIs in low PD-L1 expression CC patients. Methods: The study is an individual patient data (IPD)-based meta-analysis. IPD were compiled through KMSubtraction and IPDfromKM methodologies from high-quality randomized clinical trials and single-arm studies which reported overall survival (OS) or progression-free survival (PFS) stratified by PD-L1 expression. Kaplan-Meier curves and Cox regression analysis were employed to evaluate the survival benefits of ICIs. Results: A total of eight studies and 1110 cases were included in the analysis. Within the low PD-L1 expression subgroup, ICI combination therapy, but not ICI monotherapy, demonstrated significant OS benefits over non-ICI treatment (hazard ratio [HR] = 0.61, 95% confidence interval [CI]: 0.36-1.04, p = 0.06). Concerning PFS, ICI monotherapy was associated with a negative effect compared to non-ICI treatment (HR = 4.59, 95% CI: 2.32-9.07, p < 0.001). Notably, both OS and PFS outcomes were unfavorable for ICI monotherapy compared to both non-ICI and ICI combination therapy in the combined positive score <1 subgroup (OS: HR = 2.60, 95% CI: 1.31-5.16, p = 0.008; PFS: HR = 7.59, 95% CI: 3.53-16.31, p < 0.001). Conclusion: In patients with CC and low PD-L1 expression, ICI monotherapy may not be considered as the optimal treatment strategy when compared to non-ICI treatment or ICI combination therapy. Registration: CRD42023395103.

Perceptions, Attitudes, and Barriers to Human Papillomavirus Vaccination Among Residents in Saudi Arabia: A Cross-Sectional Study.

BACKGROUND: Human papillomavirus (HPV) infection is a prevalent sexually transmitted infection globally, with significant associations with various cancers. Despite the availability of HPV vaccines, vaccination uptake remains suboptimal in many regions, including Saudi Arabia. METHODS: This cross-sectional survey-based study aimed to assess perceptions, attitudes, and barriers related to HPV vaccination among residents in different regions of Saudi Arabia. Participants were recruited using a stratified sampling method, and data were collected through a structured questionnaire administered electronically. RESULTS: A total of 600 participants were included in the study, with diverse demographic profiles observed. The largest age group was 26-35 years old, comprising 42.7% (n = 256) of the sample. The distribution of gender was approximately equal, with 54.7% (n = 328) male participants. Notable perception and knowledge about HPV were observed, with 49.7% (n = 298) reporting being very familiar. Furthermore, 85.8% (n = 515) believed that HPV could cause serious health problems, and 63.7% (n = 382) perceived the vaccine to be very effective. Positive attitudes toward HPV vaccination were prevalent, with a significant proportion expressing a willingness to recommend the vaccine to themselves (70.0%, n = 420) and their children (65.0%, n = 390). Healthcare provider recommendation emerged as a key influencing factor, with 73.8% (n = 443) citing it as influential. Despite favorable attitudes, barriers to HPV vaccination were reported, including vaccine cost (22.5%, n = 135) and lack of awareness (13.7%, n = 82). However, a substantial proportion of unvaccinated participants cited not applicable reasons (57.2%, n = 343), indicating prior vaccination. Factors associated with HPV vaccination uptake included higher education levels, with those holding a master's degree or above exhibiting higher odds of vaccination uptake (OR (odds ratio): 1.80, 95% CI (confidence interval): 1.35-2.40, p < 0.001). Age (26-35 vs. 18-25) also showed a borderline significant association (OR: 1.25, 95% CI: 0.98-1.60, p = 0.074). CONCLUSION: The study highlights the importance of understanding perceptions and barriers to HPV vaccination to inform public health policies and programs in Saudi Arabia. Addressing identified barriers, such as educational campaigns and improving access to vaccination services, is essential for enhancing HPV vaccination coverage and reducing the burden of HPV-related diseases in the region.