Cervical Cancer Research Articles

Identifying key challenges and optimizing approaches for training of health care professionals for HPV vaccination programmes

Healthcare professionals (HCPs) play a crucial role in building vaccine confidence and promoting vaccination programmes. HCP vaccination recommendations are often the strongest predictor of vaccine uptake, influencing individuals' acceptance of and demand for vaccination. However, HCP training on human papillomavirus (HPV) vaccination faces challenges in some countries, including Ethiopia, Malawi, and Uganda. This study summarizes the discussions held during the Coalition to Strengthen HPV Immunization Community Symposium in Africa, the field experiences of co-authors, and expert opinions to inform its findings. Key challenges faced in these countries are maintaining regular and comprehensive HCP training, ensuring continuity due to staff turnover, reaching all health facilities, and including teachers as key mobilizers. Funding constraints, limited communication materials, and human resource shortages can further impact training effectiveness. Recommendations for strengthening HCP training on HPV vaccination programmes include providing adequate training to all HCPs, refresher training, including private sector HCPs and teachers, leveraging local training institutions, and integrating HPV vaccine training into pre-service HCP academic curricula. These actions would be essential for improving HPV vaccine coverage and working towards cervical cancer elimination goals.

Case studies on the progress of cervical cancer screening programs in Bhutan, India, and Türkiye

International stakeholders gathered in New Delhi, India, in December 2022 to share experiences on human papillomaviruses (HPV) prevention and control strategies. As part of a supplementary publication from the meeting proceedings, this paper describes secondary HPV prevention strategies highlighting the varying degrees of progress and challenges through case studies from Bhutan, India, and Türkiye. India has implemented national screening guidelines, primarily using visual inspection with acetic acid (VIA), but achieving a low coverage rate of 1.9% (2022). In contrast, Bhutan and Türkiye have redesigned and established HPV-based cervical screening programs targeting women aged 30–65, achieving 77% (2022) and 95% (2019) coverage among women ever screened, respectively. Lessons learned include utilising patient health information management systems, analysing optimal context-specific HPV testing strategies and ensuring use and continuous supply of clinically validated HPV tests.

Differences in Trends in Cancer Incidence Rates Among People with HIV during 2001-2019 By Race and Ethnicity and By Risk Group in the United States.

Cancer risk among people with HIV (PWH) has declined over time as a result of antiretroviral therapy, but it is unclear whether all racial/ethnic groups and transmission risk groups have experienced equal declines. We used data on PWH aged ≥20 years old from the HIV/AIDS Cancer Match Study during 2001-2019. We used Poisson regression to assess time trends in incidence rates for each cancer site by racial/ethnicity and risk group, adjusting for age, registry, and sex. We also estimated adjusted rate ratios across racial and ethnic and risk groups in 2001-2004 and 2015-2019. Trends in age-standardized rates differed across Black, White and Hispanic PWH, and across risk groups for some cancers. For example, liver cancer rates declined 23% per 5-year period among White PWH, 11% in Black PWH and 18% in Hispanic PWH. Anal cancer rates declined among men who have sex with men, were stable among people who inject drugs, and increased among other risk groups Between 2001-2004 and 2015-2019, relative difference in cancer incidence rates by race/ethnicity increased for HL and liver cancer but decreased for NHL; by risk group, relative differences increased for NHL and liver cancer, and decreased for HL, lung and anal cancers. Among PWH in the US, during 2001-2019, HL, lung, liver, and cervical cancer rate trends were different across racial/ethnic groups. HL, lung, anal, and liver cancer rates trends were different across risk groups. Future work should examine underlying causes of the differences in trends.

Integrating HPV vaccine service delivery with adolescent health programmes – Experiences and perspectives from selected countries in Africa

Primary prevention of human papillomavirus (HPV) infection is particularly important in Africa, where there is a high and accelerating burden of cervical cancer. Stakeholders have increasingly called for integration of other services with HPV vaccination in low- and middle-income countries, yet successful and sustainable integration requires intensive resource inputs, and few countries in Africa have tested integrated approaches. We describe co-author experience and previously published assessments to present the experiences of four African countries, Senegal, Togo, Tanzania, and Lesotho, with integrating HPV vaccine services with other programmes and services. The resulting case series explores how countries are operationalizing the concept of integration and describes contextual factors for success and sustainability. A simple three-level framework for describing HPV vaccine integrated service delivery has emerged to guide future endeavors.

Impact of HIV infection on cervical intraepithelial neoplasia detection in pregnant and non-pregnant women in Germany: a cross-sectional study.

Women living with HIV (WLWH) are frequently affected by cervical dysplasia caused by Human Papillomavirus (HPV) and invasive cervical cancer (CxCa). CxCa screening programs can include colposcopy, cytology, and HPV testing. These methods, however, have limitations in effectively stratifying cervical dysplasia. This study aimed to evaluate the applicability of an innovative mRNA-based multiplexed expression-quantifying assay in the detection and assessment of cervical dysplasia in WLWH. The QuantiGene-Molecular-Profiling-Histology Assay (QG-MPH) was used to detect and quantify HPV oncogene and cellular biomarker mRNA expression. These results were included in the Risk Score (QG-MPH RS) calculations that inform about the presence and severity of dysplasia. QG-MPH RS results were compared to the highly sensitive Multiplexed Papillomavirus Genotyping (MPG) Assay and clinical results obtained by cytology, colposcopy and histology. For a standardized nomenclature of clinical results, the clinical ASSIST Score was used. Of 241 WLWH, including 96 pregnant women, a concordance between the QG-MPH RS and the ASSIST Score was found to 36.3% (49/135) in non-pregnant WLWH and 67.1% (57/85) in pregnant WLWH. The QG-MPH method demonstrated high specificity for detecting high-risk HPV (HR-HPV) genotypes and high-grade cervical dysplasia, achieving 89.6% and 82.4%, respectively, including pregnant and non-pregnant WLWH. The QG-MPH assay shows potential for improving the detection and management of HPV-related cervical dysplasia in WLWH, including pregnant women. Its high specificity, however, is tempered by its tendency to overestimate dysplasia severity in certain cases, indicating that further research is needed to refine its use as a reliable diagnostic tool for this high-risk population.

Assessing the impact of cervical cancer education in two high schools in Ghana

BackgroundCervical cancer is one of the commonest female cancers in Ghana. However, it is preventable. Prevention through Human Papilloma Virus immunization and early detection by screening have their foundation in awareness and a good knowledge about the disease. Acquiring the right knowledge about cervical cancer should be earlier rather than later while mindsets are still being formed to translate into the right attitudes and behaviours later in life.MethodologyAn unpaired pre- and post-test quasi experimental study was conducted at two Ghanaian senior high schools. An educational intervention was carried out comprising a drama, PowerPoint lecture, question and answer session and cervical cancer information leaflet distribution. A self-administered questionnaire was given as a pre-test and repeated as a post-test after 3 months. The total score for each domain of knowledge tested was categorized into adequate knowledge (≥ 50%) and inadequate knowledge (< 50%).ResultsThe number of participants in the pre- and post-test were 1,107 and 1,276 girls respectively, with average age of 16 years. General knowledge on cervical cancer improved to 94.4% from 73% following the intervention, but only 46.2% said cervical cancer was curable following the education. Knowledge on symptoms improved from 78 to 87.1% and risk factor knowledge improved from 81.8 to 89.3%. After the intervention, 37% from an initial 42% still thought that having sex at a young age (adolescence) was not a risk factor. Screening and prevention knowledge improved from 82.9 to 91% but only 37.2% knew the recommended age to begin screening with pap smears, even after the education. Overall knowledge on cervical cancer after the education significantly improved from 79.1 to 92.3%.ConclusionKnowledge of cervical cancer among young girls in two High Schools, improved with the educational intervention. Areas of education to be emphasized are: cervical cancer is curable if diagnosed early, increased risk with early onset of sexual activity, and recommended age to start screening. Educating young girls on cervical cancer increases their awareness and gives them adequate knowledge which should influence their attitudes and behaviour towards cervical cancer in the future. It should be considered for adoption into high school curricula.

Histone Lactylation-Driven GPD2 Mediates M2 Macrophage Polarization to Promote Malignant Transformation of Cervical Cancer Progression.

Cervical cancer (CC) is the most common cancer in women. This study aims to explore the molecular mechanism of lactate secreted by CC cells modulating macrophage polarization in CC via histone lactylation. Normal cervical epithelium (NCE), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and cervical squamous cell carcinoma (CESC) were collected to assess H3K18la level and macrophage infiltration. Macrophages were incubated with SiHa cell-derived conditioned medium to detect M1 and M2 markers. NCE, HSIL, and CESC samples were used for ChIP-seq of H3K18la. Histone lactylation-dirven GPD2 was knocked down in macrophages. Compared to NCE, H3K18la level and M2 macrophage abundance were increased in LSIL, HSIL, and CESC. Lactate secreted by CC cells upregulated H3K18la and M2 markers but downregulated M1 markers in macrophages. ChIP-seq revealed that upregulated pathways in HSIL vs. NCE and CESC vs. HSIL were commonly enriched in lipid metabolism. Notably, lactate upregulated H3K18la-modified GPD2 expression in macrophages, and GPD2 knockdown reversed lactate induction to M2 macrophages. Collectively, lactate secreted by CC cells upregulates GPD2 via histone lactylation, thereby promoting M2 macrophage polarization in CC. This study provides new insights into the role of histone lactylation in macrophage polarization in the malignant transformation of CC.

Population-based cross-sectional survey of cervical cancer screening prevalence and socio-demographic correlates in Bangladeshi women.

Cervical cancer, albeit preventable, is the second-most deadly gynecological cancer in developing nations. Little is known about cervical cancer among Bangladeshi women. This study aims to estimate the prevalence of cervical cancer screening and demographic correlates to identify potential variabilities in screening rates among different demographic groups and regions. This study used secondary data from the WHO STEPS 2018 Survey. We used Bayesian regression to perform the bivariate analyses between the outcome and each explanatory factor, as it generates more acceptable results and improves parameter estimates. The top-ranked socio-demographic factors were identified using a two-step cluster analysis. This method determines the relevance of predictor variables and automatically establishes the number of clusters. The prevalence of Bangladeshi women who had ever been screened for cervical cancer was 6.2%. In the adjusted model, women with the following socio-demographic factors had a higher likelihood of developing cervical cancer: being 18-29 years old (AOR = 3.3, 95% CI: 0.24, 15.27) or 45-59 years old (AOR = 2.8, 95% CI: 1.22, 6.0), currently married (AOR = 2.3, 95% CI: 1.36, 3.70), and employed (AOR = 2.4, 95% CI: 1.40, 4.06). Women in the Barisal division were found to have higher odds of being screened for cervical cancer (AOR = 21, 95% CI: 0.66, 121.97). Cluster analysis found residence status predisposes women to cervical cancer screening. There is a significant potential for substantial reductions in the burden of cervical cancer in Bangladesh by strengthening the application of cervical cancer screening. Future studies should examine how socioeconomic status, culture, and healthcare access affect cervical cancer screening trends for different divisions in Bangladesh. An independent national cancer registry is urgently needed to evaluate screening trends and outcomes.

Brachytherapy for cervical cancer: from intracavitary to interstitial technique

Cervical cancer is a common malignant tumor of female reproductive system. Radiation therapy is one of the main methods of cervical cancer treatment, of which brachytherapy is an essential and important part of radiation therapy for locally advanced cervical cancer. With the rapid development of imaging technologies such as computed tomography (CT) and magnetic resonance imaging (MRI), brachytherapy for cervical cancer has gradually developed from traditional two-dimensional image-guided technology to three-dimensional image-guided technology. And there are more and more treatment methods, including intracavitary brachytherapy, interstitial brachytherapy, and intracavitary combined interstitial implantation brachytherapy. We performed a PubMed search for introduce the application progress of intracavity, implantation, intracavity combined implantation brachytherapy and radioactive seed implantation, and discuss the dosimetric feasibility of internal and external fusion irradiation.

Automatic delineation of cervical cancer target volumes in small samples based on multi-decoder and semi-supervised learning and clinical application

Radiotherapy has been demonstrated to be one of the most significant treatments for cervical cancer, during which accurate and efficient delineation of target volumes is critical. To alleviate the data demand of deep learning and promote the establishment and promotion of auto-segmentation models in small and medium-sized oncology departments and single centres, we proposed an auto-segmentation algorithm to determine the cervical cancer target volume in small samples based on multi-decoder and semi-supervised learning (MDSSL), and we evaluated the accuracy via an independent test cohort. In this study, we retrospectively collected computed tomography (CT) datasets from 71 pelvic cervical cancer patients, and a 3:4 ratio was used for the training and testing sets. The clinical target volumes (CTVs) of the primary tumour area (CTV1) and pelvic lymph drainage area (CTV2) were delineated. For definitive radiotherapy (dRT), the primary gross target volume (GTVp) was simultaneously delineated. According to the data characteristics for small samples, the MDSSL network structure based on 3D U-Net was established to train the model by combining clinical anatomical information, which was compared with other segmentation methods, including supervised learning (SL) and transfer learning (TL). The dice similarity coefficient (DSC), 95% Hausdorff distance (HD95) and average surface distance (ASD) were used to evaluate the segmentation performance. The ability of the segmentation algorithm to improve the efficiency of online adaptive radiation therapy (ART) was assessed via geometric indicators and a subjective evaluation of radiation oncologists (ROs) in prospective clinical applications. Compared with the SL model and TL model, the proposed MDSSL model displayed the best DSC, HD95 and ASD overall, especially for the GTVp of dRT. We calculated the above geometric indicators in the range of the ground truth (head-foot direction). In the test set, the DSC, HD95 and ASD of the MDSSL model were 0.80/5.85 mm/0.95 mm for CTV1 of post-operative radiotherapy (pRT), 0.84/ 4.88 mm/0.73 mm for CTV2 of pRT, 0.84/6.58 mm/0.89 mm for GTVp of dRT, 0.85/5.36 mm/1.35 mm for CTV1 of dRT, and 0.84/4.09 mm/0.73 mm for CTV2 of dRT, respectively. In a prospective clinical study of online ART, the target volume modification time (MTime) was 3–5 min for dRT and 2–4 min for pRT, and the main duration of CTV1 modification was approximately 2 min. The introduction of the MDSSL method successfully improved the accuracy of auto-segmentation for the cervical cancer target volume in small samples, showed good consistency with RO delineation and satisfied clinical requirements. In this prospective online ART study, the application of the segmentation model was demonstrated to be useful for reducing the target volume delineation time and improving the efficiency of the online ART workflow, which can contribute to the development and promotion of cervical cancer online ART.

Disparities in Cervical Cancer Knowledge and Trust in Information Sources Among Diverse American Women.

Cervical cancer rates have declined due to prevention and screening, but disparities remain. This study examines how trust and preference in information sources affect knowledge and behaviors, alongside demographic differences to identify health disparities. This study used Health Information National Trends Survey data and employed weighted chi-square tests and multivariate logistic regression to analyze associations between knowledge, behaviors, and demographic differences. The results revealed significant disparities in HPV awareness, with lower awareness among Black (OR, 0.521), Hispanic (OR, 0.398), and Asian (OR, 0.138) women compared to Whites. Age and education also played roles, as older and less-educated women were less informed. Trust in doctors was crucial; women with low trust in doctors (aOR, 0.499; 95% CI, 0.252-0.989) had lower odds of having heard of HPV. Preference for written materials as a primary information source (aOR, 0.312; 95% CI, 0.122-0.793) also correlated with lower HPV awareness compared to preferring information from doctors. Furthermore, women with low trust in charity organizations (aOR, 0.647; 95% CI, 0.461-0.909) were less likely to believe HPV causes cervical cancer, while those who preferred the internet as an information source (aOR, 1.544; 95% CI, 1.026-2.324) had higher odds of having heard of HPV compared to those preferring doctors. Minority populations, older women, and those with lower education levels had significantly lower HPV knowledge. These findings highlight the need for tailored communication, community outreach, policy initiatives, culturally sensitive approaches, digital health interventions, and strategies promoting patient-provider trust to address these disparities.

Development and validation of the competing risk nomogram and risk classification system for predicting cancer-specific mortality in patients with cervical adenosquamous carcinoma treated via radical hysterectomy.

In this study, we established and validated a competing risk nomogram for predicting the cumulative incidence of cervical adenosquamous carcinoma (ASC)-specific death in patients undergoing radical hysterectomy. Patients diagnosed with ASC between 2010 and 2019 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The cumulative incidence function (CIF) for various variables influencing ASC-specific mortality was computed. A Fine-Gray competing risk model was used to identify independent predictors, formulating a competing risk nomogram. A multivariate Cox proportional hazards model was also applied for comparative analysis. The performance of the nomogram was assessed using metrics such as the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). A corresponding risk classification system was constructed based on nomogram-derived scores. Factors such as advanced age, racial background (Black race), higher tumor grade, increased tumor size, advanced TNM stage, and receipt of radiotherapy without chemotherapy were found to be positively associated with elevated ASC-specific mortality. Additionally, age, T stage, M stage, and chemotherapy were identified as independent predictors correlated with ASC-specific mortality. The established nomogram exhibited accurate discriminatory capabilities and superior net benefits compared to the traditional TNM staging system. Additionally, the high-risk group consistently demonstrated higher probabilities of ASC-specific death in both the training and validation sets. The developed nomogram proficiently quantified the incidence of ASC-specific death in patients subjected to radical hysterectomy for ASC. This tool could help clinicians in formulating personalized treatment strategies and devising follow-up protocols.

Construction of a nomogram for personalized prediction of lower limb lymphedema risk after cervical cancer surgery

ObjectiveThis study aims to construct and evaluate an individualized nomogram for predicting the risk of lower limb lymphedema after cervical cancer surgery. Healthcare professionals can utilize line chart models to predict the probability of postoperative lower limb lymphedema in different patients, allowing for the early identification of high-risk patients and facilitating early prevention and treatment.MethodsA retrospective study was conducted among 411 cervical cancer patients treated at our hospital from May 2021 to December 2023. The patients were randomly divided into a modeling group (313 cases) and a validation group (98 cases) according to an approximate 3:1 ratio. The modeling group was further divided into a lower limb lymphedema group (61 cases) and a non-lower limb lymphedema group (252 cases) based on the presence of postoperative lower limb lymphedema. Multiple factors Logistic regression was used to identify risk factors, and a nomogram was constructed using R software version 4.0.2, with internal and external validation performed.ResultsRisk factors for lower limb lymphedema following cervical cancer surgery include age 60 years or older, a Body Mass Index (BMI) of 24 kg/m² or higher, hypertension, the removal of 30 or more lymph nodes, adjuvant radiotherapy and chemotherapy, and prolonged standing for six hours or more (P < 0.05). Internal and external validation results demonstrated that the calibration curve closely aligned with the ideal curve. The Area Under Curve(AUC) of the Receiver Operating Characteristic(ROC) curve was 0.890 (95% CI: 0.844 ∼ 0.936) and 0.876 (95% CI: 0.821 ∼ 0.930), indicating high model calibration and discrimination. Decision Curve Analysis(DCA) curve revealed that the Logistic model had good net returns and high clinical practicality when the probability range of the high-risk threshold was 0.11 ∼ 0.98.ConclusionThe nomogram, developed using factors such as age, BMI, hypertension, number of lymph nodes dissected, adjuvant radiotherapy and chemotherapy, and duration of standing, has strong predictive value and offers significant clinical benefits, making it a valuable tool for clinical decision-making.

Systemic hormone therapy after breast and gynecological cancers: an Italian expert group consensus opinion.

The specific Italian Group of Study of the Menopause formulated a consensus opinion on the use of estrogen therapy (ET) or combined estro-progestin hormone therapy (HT) after breast and gynecological cancers. This consensus is based on the risk of recurrence of the specific cancer during ET/HT, the presence of steroid receptors in cancer cells, the use of adjuvant hormone therapies and data on the use of ET/HT after cancer. The following positions were reached. ET/HT can be used after vulvar cancers and melanoma, but with great caution after the rare adenocarcinomas. ET/HT can be used after cervical cancer, but ET should be used with caution after adenocarcinomas. ET/HT can be used after International Federation of Obstetrics and Gynecology (FIGO) stage I-II estrogen-dependent endometrial cancers, except in Black women, and can probably be used after estrogen-independent endometrial cancers. ET/HT cannot be administered or should be used with great caution after most uterine sarcomas. ET/HT can probably be used after ovarian neoplasms except for granulosa cell tumors, and with great caution after low-grade serous ovarian carcinoma and serous borderline ovarian tumors. ET/HT can be used with great caution in women after estrogen receptor (ER)/progesterone receptor (PR)-positive breast cancer and is probably allowed after ER/PR-negative breast cancer.

Edge computing-based ensemble learning model for health care decision systems

A growing number of humans have suffered severe chronic illnesses, which has caused a boost in the requirement for diagnostic and medical treatment procedures that are both accurate and fast. Improved patient conditions and enhanced Decision-Making Systems (DMS) for healthcare professionals are the primary objectives of the Clinical Decision Support System (CDSS) recommended in this research article. The main drawback of traditional Machine Learning (ML) techniques is their failure to predict reliably. To solve this problem, the proposed model creates an Ensemble Extreme Learning Machine (EN-ELM) algorithm that combines predictors trained on several different data sets. This lowers the chance of overfitting. The suggested CDSS uses many different data processing methods, including Adaptive Synthetic (ADASYN) and isolation Forest (iForest), which fix problems like outliers and class imbalance. This approach significantly enhances the framework’s classification performance. Also, the CDSS is compatible with an EC model, which enables real-time computation while minimizing the requirement for integrated systems. The recommended CDSS applies iForest and ADASYN to execute large-scale trials validating high standards of accuracy across numerous datasets. Researchers concluded that a suitable ELM classification threshold of 85% is the most effective, which substantially boosts the accuracy of the predictive model. When applied to various medical datasets, such as Hepatocellular Carcinoma (HCC), Cervical Cancer, Chronic Kidney Disease (CKD), Heart Disease, and Arrhythmia, the EN-ELM achieved accuracy rates of 99.36%, 98.15%, 97.85%, 97.06%, and 96.72%, respectively. By measuring this progress, the CDSS could dramatically improve the accuracy of chronic illness diagnosis and treatment, which similarly affects clinicians.

Factors associated with cervical cancer screening among women attending gynecological consultations at the Maroua Regional Hospital, Cameroon

This study aimed to assess the factors associated with cervical cancer screening at the Maroua Regional Hospital. A cross-sectional study was conducted among 376 women aged &amp;ge;25 years attending gynecological consultations at the Maroua Regional Hospital between February and May 2023. Data were collected through a structured questionnaire survey. These factors were evaluated through multiple logistic regression analyses, and associations were established by calculating the odds ratios, confidence intervals, and p-values. A total of 376 women were interviewed. Their mean age was 39.21 &amp;plusmn; 10.45 years. Of the 376 women, 9.3% had already been screened for cervical cancer. Results of multivariate analyses indicated that age &amp;ge;45 years, belief that every woman should be screened at age 25 years, perceived need for frequent screening, use of screening as a preventive measure, and having had first intercourse before age 15 years or between ages 15 and 20 years significantly increased the likelihood of having been screened. Strategies need to be developed to improve access to cervical cancer screening services in Cameroon by strengthening existing screening programs and effectively implementing campaigns to improve access to screening services.

Pros and cons of digital access to healthcare services and healthcare utilization: a quasi-experiment

ObjectivesWe study the introduction of a web portal allowing women to manage their appointments in the public cervical cancer screening program of an Italian Local Health Unit (LHU). We investigate how this intervention affects program participation and the ability of the LHU to collect information on women's screening outside the program.MethodsWe use administrative data from the LHU and a difference-in-differences design to compare outcomes of women in the treated group (n=870), who could reschedule appointments either through phone calls or through the portal, and the control group (n=768), who could only reschedule by phone.ResultsThe portal reduces the number of appointments rescheduled by phone (b = −0.176, 95% CI = −0.228 to −0.114, p &amp;lt; 0.001). It also makes women more likely to report both screenings outside the program (b = 0.049, 95% CI = 0.006–0.912, p &amp;lt; 0.05) and the various reasons for canceling their appointments. However, the portal also decreases the probability of screening (b = −0.156, 95% CI = −0.216–0.096, p &amp;lt; 0.001). Two-thirds of this reduction is due to increased unjustified no-shows (b = 0.099, 95% CI = 0.043–0.155, p &amp;lt; 0.001).ConclusionsDigital innovations increase efficiency of screening programs. However, they may discourage screening, by triggering behavioral biases such as limited attention and procrastination. Pairing portals with frequent reminders may help to boost participation.

Supply-Side Barriers in Accessing Human Papillomavirus Screening for Cervical Cancer Prevention in Rural India: Evidence From a Cross-Sectional Study

Supply-Side Barriers in Accessing Human Papillomavirus Screening for Cervical Cancer Prevention in Rural India: Evidence From a Cross-Sectional Study

An Investigation of RNA Methylations with Biophysical Approaches in a Cervical Cancer Cell Model

RNA methylation adds a second layer of genetic information that dictates the post-transcriptional fate of RNAs. Although various methods exist that enable the analysis of RNA methylation in a site-specific or transcriptome-wide manner, whether biophysical approaches can be employed to such analyses is unexplored. In this study, Fourier-transform infrared (FT-IR) and circular dichroism (CD) spectroscopy are employed to examine the methylation status of both synthetic and cellular RNAs. The results show that FT-IR spectroscopy is perfectly capable of quantitatively distinguishing synthetic m6A-methylated RNAs from un-methylated ones. Subsequently, FT-IR spectroscopy is successfully employed to assess the changes in the extent of total RNA methylation upon the knockdown of the m6A writer, METTL3, in HeLa cells. In addition, the same approach is shown to accurately detect reduction in total RNA methylation upon the treatment of HeLa cells with tumor necrosis factor alpha (TNF-α). It is also demonstrated that m1A and m6A methylation induce quite a distinct secondary structure on RNAs, as evident from CD spectra. These results strongly suggest that both FT-IR and CD spectroscopy methods can be exploited to uncover biophysical properties impinged on RNAs by methyl moieties, providing a fast, convenient and cheap alternative to the existing methods.

Chemical Profile of Kumquat (Citrus japonica var. margarita) Essential Oil, In Vitro Digestion, and Biological Activity

Kumquat is one of the smallest citrus fruits (from the Rutaceae family), and its essential oil’s biological effects have not yet been sufficiently researched, in contrast to the essential oils of its relatives. Therefore, the aim of this large-scale study was to investigate the chemical profile of kumquat essential oils (KEOs) isolated by microwave-assisted distillation (MAD) and Clevenger hydrodistillation using GC-MS analysis. To test the bioaccessibility of their bioactive components, in vitro digestion with commercially available enzymes was performed. The final step of this research was to test their cytotoxic activity against a cervical cancer cell line (HeLa), a human colon cancer cell line (HCT116), a human osteosarcoma cell line (U2OS), and a healthy cell line (RPE1). Two methods were used to test the antioxidant activity: DPPH (2,2-diphenyl-1-picrylhydrazyl) and ORAC (oxygen radical absorbance capacity). The antibacterial activity was tested in relation to the growth and adhesion of Escherichia coli and Staphylococcus aureus on a polystyrene surface. The GC-MS analysis showed that the major compound in both kumquat essential oils was limonene, which was stable before and after in vitro digestion (&gt;90%). The results showed that the cytotoxic activity of the KEOs in all three cancer cell lines tested was IC50 1–2 mg/mL, and in the healthy cell line (RPE1), the IC50 value was above 4 mg/mL. The antibacterial activity of the KEOs obtained after MAD and Clevenger hydrodistillation was 4 mg/mL against E. coli and 1 mg/mL against S. aureus. The KEOs after MAD and Clevenger hydrodistillation reduced the adhesion of E. coli by more than 1 log, while there was no statistically significant effect on the adhesion of S. aureus to the polystyrene surface. Both KEOs exhibited comparable levels of antioxidant activity using both methods tested, with IC50 values of 855.25 ± 26.02 μg/mL (after MAD) and 929.41 ± 101.57 μg/mL (after Clevenger hydrodistillation) for DPPH activity and 4839.09 ± 91.99 μmol TE/g of EO (after MAD) and 4928.78 ± 275.67 μmol TE/g of EO (after Clevenger hydrodistillation) for ORAC. The results obtained show possible future applications in various fields (e.g., in the food, pharmaceutical, cosmetic, and agricultural industries).