Sensitivity, Specificity, and Cost-Benefit Effect Between Primary Human Papillomavirus Testing, Primary Liquid-Based Cytology, and Co-Testing Algorithms for Cervical Lesions.

BACKGROUND: Cytology has long been a major screening method for cervical cancer prevention. Human papillomavirus (HPV) testing has recently been introduced for cervical cancer screening, and HPV tests become a major screening method in some countries. To seek the optimal strategy considering the cost-effectiveness for cervical cancer screening, we compared the performance of primary LBC, primary HPV test, and LBC plus HPV co-test in real practice. METHODS: From March 2016 to June 2018, 3742 patients were included in this study. Liquid-based cytology (LBC), HPV test, and histopathological assessment were performed in 3727, 1063, and 508 cases, respectively. The sensitivity, specificity, and cost-benefit effects of primary HPV, primary LBC, and co-test algorithms were simulated for 317 cases with LBC, HPV, and histopathological results. RESULTS: On the LBC, 13.0% of the cases were diagnosed with atypical squamous cells of undetermined significance or higher grade lesions. In the HPV test, high-risk HPV was found in 43.5%, and 11.9% was positive for HPV type 16 or 18. Among the three simulated algorithms, the co-test demonstrated the best sensitivity (97.5%) and the lowest specificity (50.3%). The primary LBC demonstrated the best specificity (53.5%) and a slightly better sensitivity, compare with the primary HPV (95.1% vs. 93.8%). Using the primary LBC algorithm, 82.0% can be determined without additional HPV test, whereas 50.1% could be determined without additional LBC using the primary HPV algorithm. CONCLUSIONS: The primary LBC algorithm for uterine cervical cancer (UCC) screening is comparable to the primary HPV algorithm and has the best cost-benefit effect among the three algorithms.

Advancing epigenetic profiling in cervical cancer: machine learning techniques for classifying DNA methylation patterns.

This study investigates the ability to predict DNA methylation patterns in cervical cancer cells using decision-tree-based ensemble approaches and neural network-based models. The research findings suggest that a model based on random forest achieves a significant prediction accuracy of 91.35%. This projection was derived from comprehensive experimentation and a meticulous performance evaluation of the random forest model, employing a range of measures including Accuracy, Sensitivity, Specificity, Matthews Correlation Coefficient, F1-score, Recall, and Precision. The results indicate that the random forest model exhibits superior performance compared to other tree-based models such as the Simple Decision Tree and XGBoost, as well as neural network-based models including Convolutional Neural Networks, Feed Forward Networks, and Wavelet Neural Networks. The findings indicate that using random forest-based techniques has great potential for future study and might be highly valuable in clinical applications, especially in improving diagnostic and treatment strategies based on epigenetic profiles.

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.

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.

Combination therapy with paclitaxel and trastuzumab for human epidermal growth factor receptor 2-positive recurrent serous carcinoma of the uterine cervix: A case report.

Recent studies show increased expression of human epidermal growth factor receptor 2 (HER2) in cervical cancer, but the efficacy of anti-HER2 therapy remains under-researched. Here, we present a case of recurrent HER2-positive serous carcinoma, presumably arising in the cervix, diagnosed by comprehensive genomic profiling, which responded to trastuzumab. The patient underwent a radical hysterectomy with concurrent adjuvant chemoradiotherapy. One year after surgery, the patient experienced recurrence (multiple lymph node metastases). She underwent chemotherapy and subsequent comprehensive genomic profiling, which revealed HER2 positivity. Despite treatment, the lymph node and peritoneal metastases progressed. Therefore, combination chemotherapy with paclitaxel and trastuzumab was initiated. Subsequently, the patient's clinical symptoms improved considerably, and good health was maintained for 8 months. This report highlights the importance of comprehensive genomic profiling and targeted therapies when standard treatments fail.

Investigating and Analyzing Prognostic Factors and Their Impact on Recurrent Cervical Cancers.

The incidence of cervical cancer in India is significantly high, and the average recurrence age is much less. The standard line of treatment consists of concurrent chemoradiotherapy. If a recurrence occurs, the treatment options or set of interventions are limited and suboptimal. Through this review, we have analyzed and classified the possible prognostic factors for cervical cancer into three broad categories, viz., (a) disease-related factors, (b) patient-related factors, and (c) treatment-related factors. Disease-related factors include tumor histology, tumor size, stage, parametrial involvement (PMI), Prognostic Nutritional Index (PNI), lymphovascular space invasion (LVSI), and nodal status. Patient-related factors include overall treatment time (OTT), nutritional status, hemoglobin level, comorbidities, and age. Treatment-related factors include addition of chemotherapy, techniques of external beam radiotherapy (EBRT), techniques of brachytherapy, and quality assurance for radiation therapy delivery. Out of these, extremely significant prognostic factors were tumor size and stage, nodal status, PMI, nutritional status, and addition of chemotherapy. Impactful factors include younger age, histology, LVSI, associated comorbidities, hemoglobin level, OTT, and patient-specific quality assurance. The factor that is not related or significant is the technique used for EBRT and brachytherapy delivery.

Predicting recurrence in intermediate­ and high­risk stage IB­IIB cervical cancer treated with adjuvant cisplatin and paclitaxel chemotherapy post­radical hysterectomy: The role of TBX2 expression.

Cervical cancer remains a significant global health concern despite advances in prevention and treatment. Current management for intermediate- to high-risk stage IB-IIB cervical cancer post-radical hysterectomy involves irradiation or concurrent chemoradiation, although patients can exhibit several adverse events. Adjuvant chemotherapy has emerged as a promising alternative; however, its efficacy remains unclear. T-box (TBX)2 is a transcription factor that is involved in the regulation of cell cycle progression during cancer and embryonic development. Additionally, elevated expression of TBX2 is associated with resistance to DNA-damaging chemotherapeutic agents, such as cisplatin, carboplatin and doxorubicin. The aim of the present study was to investigate the relationship between TBX2 expression and recurrence in patients receiving adjuvant cisplatin and paclitaxel (TP) chemotherapy post-radical hysterectomy. Additionally, the impact of TBX2 knockdown on cisplatin sensitivity was assessed in vitro. A retrospective analysis was performed on 100 patients. Patients were categorized into two groups based on recurrence within 2 years of treatment initiation: The non-recurrent group (n=85) and the recurrent group (n=15). TBX2 expression was assessed immunohistochemically, and multiple logistic regression analysis was performed to identify predictors of recurrence. Additionally, the impact of small interfering RNA-mediated TBX2 knockdown on cervical cancer cell sensitivity to cisplatin was evaluated. TBX2 expression was significantly higher in the recurrent group compared with that in the non-recurrent group (P<0.01). Patients were stratified into low TBX2 expression (weighted score ≤8; n=80) and high TBX2 expression (weighted score ≥9; n=20) groups. The high TBX2 expression group exhibited a higher recurrence rate compared with the low expression group (P<0.01). Multivariate analysis identified TBX2 expression as an independent predictor of recurrence (P<0.01). Moreover, TBX2 knockdown significantly enhanced cervical cancer cell sensitivity to cisplatin in vitro (P<0.05). These findings highlight TBX2 expression as a potential predictive biomarker for recurrence amongst patients with intermediate- to high-risk stage IB-IIB cervical cancer receiving adjuvant TP chemotherapy post-radical hysterectomy.

Successful management of locally advanced cervical cancer via total pelvic exenteration following neoadjuvant chemotherapy.

Stage IVA cervical cancer is a tumor that invades the mucosa of the bladder or rectum without distant metastasis and is difficult to treat, and concurrent chemoradiotherapy is recommended. Although radical surgery following neoadjuvant chemotherapy is a treatment option for stage IVA cervical cancer, the evidence is limited. A 51-year-old woman with bulky cervical cancer and rectal invasion was referred to our hospital. Paclitaxel and cisplatin were administered as neoadjuvant chemotherapies. After two cycles of chemotherapy, the tumor size decreased markedly. Total pelvic exenteration was performed, and a complete resection was achieved. Four cycles of paclitaxel and cisplatin were administered postoperatively. Thirty-three months after the completion of adjuvant chemotherapy, the patient was alive and free of disease. Radical surgery after neoadjuvant chemotherapy may be a treatment option for stage IVA cervical cancer with bulky tumors.

A transversal cross-sectional study of factors related to HPV vaccination status and cancer screening participation among French women aged 25-40.

BACKGROUND: In 2020, uterine cervical cancer (UCC) was the 12th most common cancer among women in France and the 4th worldwide. French health authorities wanted to increase Human Papilloma Virus (HPV) vaccination and screening rates. There were still many barriers to these measures among young women, their families, and health professionals and teachers. Between 2014 and 2019, international studies found inconsistent effects of HPV vaccination on UCC screening. In 2022, a survey was conducted among women aged 25 to 40 in the Nord-Pas-de-Calais region to assess participation 1) in HPV vaccination and its barriers, 2) in UCC screening as a function of HPV vaccination status. METHODS: Data were collected using an anonymous online questionnaire distributed by QR code in 80 general practices randomly selected in the Nord-Pas-de-Calais region between January and June 2022. Results were analyzed bivariately using the Chi2 test, multivariately when numbers allowed, and in age subgroups (sensitivity analysis). RESULTS: 407 complete questionnaires (for 602 participating women) were analyzed. In our sample, 41% of women aged 25 to 40 in the Nord-Pas-de-Calais region were vaccinated against HPV viruses in 2022. The risk factors for non-vaccination, after multivariable adjustment, were: the periods of eligibility for vaccination in the early days of French vaccination (2007-2012: odds ratio OR = 0.04 [95% CI, 0.02-0.09]; 2012-2017: OR = 0.5 [0.3-0.8]), information received from non-medical sources (OR = 0.3 [0.2-0.6]), and absence of information about vaccination (OR = 0.12 [0.05-0.27]). In our sample, 90% of women were screened for UCC. In bivariate analysis, women at risk of not being screened were those who were youngest, had been vaccinated against HPV, were not heterosexual, lived alone, had gynecological follow-up by their general practitioner, and did not have regular gynecological follow-up. Sensitivity analysis showed that the only risk factor significantly correlated with non-screening regardless of age group was lack of regular gynecological follow-up. CONCLUSIONS: Participation in HPV vaccination and UCC screening is improved by medical education and gynecological follow-up. This multicenter study, limited by the relative youth of vaccination in France, should be repeated after 2037 to assess the possible effect of vaccination on screening.

Feasibility and Diagnostic Accuracy of Ultrastaging in the Detection of Micrometastases in Sentinel and Non-sentinel Lymph Nodes in Cervical Cancer: A Single-Center Retrospective Study With a Five-Year Follow-Up Period.

BACKGROUND: Cervical cancer is the fourth most common cause of malignant tumor-related deaths among women in developing nations. Cervical cancer has been estimated to cause 527.600 new cases and 265.700 deaths globally per year. OBJECTIVES: This study aimed to evaluate patients with cervical cancer by ultrastaging all the lymph nodes (LN), sentinel LN (SLN) and non-SLN, to increase the sensitivity of the detection of LN metastases and the diagnostic accuracy in cervical cancer with a five-year follow-up. MATERIALS AND METHODS: This is a retrospective study of 14 cervical cancer cases from 2017 to 2019 at the Municipal Emergency Clinical Hospital of Timisoara, Romania. The cases were selected based on their high risk of LN involvement but negative intraoperative pathologic LN. After re-evaluating all paraffin block biopsy samples from 29 cases, 14 cases were included in the study, which met all criteria for ultrastaging on surgical biopsy samples. RESULTS: Patients' ages included in the study ranged from 43 to 70 years (median: 57.14 years). According to the International Federation of Gynecology and Obstetrics (FIGO) staging, the majority of the patients were in stage IB: seven cases (50%). The study revealed a positive correlation between patient age and FIGO staging, with Pearson's correlation coefficient of 0.707 and a p-value of less than 0.05, indicating that older patients were more likely to be diagnosed with a higher FIGO stage. The mean follow-up was 34.5 months, and the median follow-up was 36 months (range: 6-60 months). We obtained 167 nodes, with a mean of 11.92 nodes/case. Twenty-one LN were found to be positive with the ultrastaging method. We detected 11 LN with macrometastases (MAC) (52.38%), seven with micrometastasis (MIC) (33.3%), and three with tumor cell islets (14.4%). That would be 13% of newly diagnosed ultrastaging cases as positive nodes. This ultrastaging method detected nodal MIC in eight (57.1%) out of the 14 patients, who initially tested negative for LN involvement using the routine Hematoxylin and Eosin (HE) method. The detection of micrometastases in these patients underscored the superior sensitivity of ultrastaging, which was further highlighted by the subsequent relapse of four (28.57%) out of these eight patients. The study also found no correlation between the FIGO standardization and the number of MIC found in these patients. CONCLUSIONS: Predicting cervical LN metastasis (LNM) is crucial for improving survival rates and reducing recurrence. Very few small cohort studies used an ultrastaging method to assess non-SLNs; most of them only assessed SLNs. We showed in our study that the ultrastaging method, both in the case of SLN and non-SLN, is superior compared with H&E analysis, with a 13% rate of new positive nodule diagnosis. Metastatic involvement of non-SLN was found in over 50% of all cases (8/14) according to the ultrastaging method. Additionally, our study confirms that the sensitivity of SLN ultrastaging is high for the presence of both MIC and MAC in SLN pelvic LN. As a result, we feel that ultrastaging is the most effective method for SLN analysis in patients with early-stage cervical cancer, and bilateral detection is preferable, significantly reducing false-negative results. The routine use of SLN along with ultrastaging would lead to more accurate surgical staging and better oncological follow-up of cases.

Cervical Cancer in Mexico: From a Renowned Vaccination Program to Unfulfilled Needs in Treatment Access.

Mexico's national human papillomavirus (HPV) vaccination program was established in 2008, providing free access to HPV vaccines and quickly becoming an immense success story, achieving significant coverage among young Mexican females. However, despite these efforts and notable achievements, cervical cancer caused mainly by HPV remains a challenging issue among Mexican women aged 15 years or older. A critical obstacle faced by women in the country is a lack of early detection and screening resources, coupled with delays in diagnosis and treatment, exacerbated by the poor distribution of already insufficient healthcare resources. This situation creates adverse conditions for the female demographic in the country. Our editorial aims to draw attention to the urgent need to improve access to adequate prevention, screening, and treatment for cervical cancer patients in Mexico, advocating for a collective effort between the Mexican government, public health professionals, and civil society.

Preliminary result of combined treatment with scanning carbon-ion radiotherapy and image-guided brachytherapy for locally advanced cervical adenocarcinoma.

Although there is growing evidence of the efficacy of carbon-ion radiotherapy (CIRT) for locally advanced cervical adenocarcinoma, reports on combined treatment with CIRT and image-guided brachytherapy (IGBT) are scarce. We retrospectively analyzed patients with International Federation of Gynecology and Obstetrics (2008) stage II-IVA locally advanced cervical adenocarcinoma who received combined scanning CIRT (sCIRT) and IGBT between April 2019 and March 2022. sCIRT consisted of whole-pelvic irradiation with 36 Gy (relative biological effectiveness [RBE]) in 12 fractions and subsequent local boost irradiation with 19.2 Gy (RBE) in 4 fractions. Three sessions of IGBT were administered after completion of sCIRT. Concurrent chemotherapy using weekly cisplatin (40 mg/m2/week) was also administered. Efficacy, toxicity and dose-volume parameters were analyzed. Fifteen patients were included in the analysis. The median follow-up period was 25 months. The 2-year overall survival, progression-free survival and local control rates were 92.3% (95% confidence interval [CI] = 77.8-100%), 52.5% (95% CI = 26.9-78.1%) and 84.8% (95% CI = 65.2-100%), respectively. Neither severe acute toxicity necessitating treatment cessation nor grade 3 or higher late toxicity were observed. The sigmoid D2cm3 of the patient who developed grade 2 late sigmoid hemorrhage was 65.6 Gy, which exceeded the standard deviation and target dose. The combination of sCIRT and IGBT for locally advanced cervical adenocarcinoma showed acceptable efficacy and safety. Further large-scale and long-term studies are warranted to confirm the efficacy and safety of this treatment.

Evolution of Pathological Techniques for the Screening of Cervical Cancer: A Comprehensive Review.

The evolutionary journey of cervical cancer screening has been a major medical success story, considering the substantial role it has played in dwindling the disease burden. Through sustained collaborative efforts within the medical community, significant advances have been made from the humble yet path-breaking conventional Pap smear to the current automated screening systems and human papillomavirus (HPV) molecular testing. With the integration of artificial intelligence into screening techniques, we are currently at the precipice of circumventing the pitfalls of manual cytology readings and improving the efficiency of the screening systems by a significant margin. Despite the technological milestones traversed, the high logistics and operational cost, besides the technical know-how of operating the automated systems, can pose a major practical challenge in the widespread adoption of these advanced techniques in cervical cancer screening programs. This would suggest the need to adopt strategies that are tailored to the demands and needs of the different settings keeping their limitations in mind. This review aims to take the reader through the entire evolutionary journey of cervical cancer screening programs, highlight the individual merits and demerits of each technique, and discuss the recommendations from the major global guidelines.

Bone Marrow Sparing by Intensity Modulated Proton Beam Therapy in Postoperative Irradiation of Gynecologic Malignancies.

Purpose: The aim of this matched-pair cohort study was to evaluate the potential of intensity-modulated proton therapy (IMPT) for sparring of the pelvic bone marrow and thus reduction of hematotoxicity compared to intensity-modulated photon radiotherapy (IMRT) in the setting of postoperative irradiation of gynaecological malignancies. Secondary endpoint was the assessment of predictive parameters for the occurrence of sacral insufficiency fractures (SIF) when applying IMPT. Materials and Methods: Two cohorts were analyzed consisting of 25 patients each. Patients were treated with IMPT compared with IMRT and had uterine cervical (n = 8) or endometrial cancer (n = 17). Dose prescription, patient age, and diagnosis were matched. Dosimetric parameters delivered to the whole pelvic skeleton and subsites (ilium, lumbosacral, sacral, and lower pelvis) and hematological toxicity were evaluated. MRI follow-up for evaluation of SIF was only available for the IMPT group. Results: In the IMPT group, integral dose to the pelvic skeleton was significantly lower (23.4GyRBE vs 34.3Gy; p < 0.001), the average V5Gy, V10Gy, and V20Gy were reduced by 40%, 41%, and 28%, respectively, compared to the IMRT group (p < 0.001). In particular, for subsites ilium and lower pelvis, the low dose volume was significantly lower. Hematotoxicity was significantly more common in the IMRT group (80% vs 32%; p = 0009), especially hematotoxicity ≥ CTCAE II (36% vs 8%; p = 0.037). No patient in the IMPT group experienced hematotoxicity > CTCAE II. In the IMPT cohort, 32% of patients experienced SIF. Overall SIF occurred more frequently with a total dose of 50.4 GyRBE (37.5%) compared to 45 GyRBE (22%). No significant predictive dose parameters regarding SIF could be detected aside from a trend regarding V50Gy to the lumbosacral subsite. Conclusion: Low-dose exposure to the pelvic skeleton and thus hematotoxicity can be significantly reduced by using IMPT compared to a matched photon cohort. Sacral insufficiency fracture rates appear similar to reported rates for IMRT in the literature.

Findings and Challenges in Replacing Traditional Uterine Cervical Cancer Diagnosis with Molecular Tools in Private Gynecological Practice in Mexico.

We have been encouraging practicing gynecologists to adopt molecular diagnostics tests, PCR, and cancer biomarkers, as alternatives enabled by these platforms, to traditional Papanicolaou and colposcopy tests, respectively. An aliquot of liquid-based cytology was used for the molecular test [high-risk HPV types, (HR HPV)], another for the PAP test, and one more for p16/Ki67 dual-stain cytology. A total of 4499 laboratory samples were evaluated, and we found that 25.1% of low-grade samples and 47.9% of high-grade samples after PAP testing had a negative HR HPV-PCR result. In those cases, reported as Pap-negative, 22.1% had a positive HR HPV-PCR result. Dual staining with p16/Ki67 biomarkers in samples was positive for HR HPV, and 31.7% were also positive for these markers. Out of the PCR results that were positive for any of these HR HPV subtypes, n 68.3%, we did not find evidence for the presence of cancerous cells, highlighting the importance of performing dual staining with p16/Ki67 after PCR to avoid unnecessary colposcopies. The encountered challenges are a deep-rooted social reluctance in Mexico to abandon traditional Pap smears and the opinion of many specialists. Therefore, we still believe that colposcopy continues to be a preferred procedure over the dual-staining protocol.

Role of the gel spacer in safely delivering whole pelvic radiation therapy without central shielding in computed tomography-based image-guided adaptive brachytherapy for uterine cervical cancer patients.

BACKGROUND: To protect the rectum and bladder from high dose exposure, the Japanese guidelines for managing uterine cervical carcinoma recommend pelvic irradiation with central shielding (CS). Conversely, the European Society for Radiotherapy and Oncology (ESTRO) and the American Brachytherapy Society (ABS) guidelines recommend delivering ≥85 Gy to high-risk clinical target volume D90 (CTVHR D90%). In this study, we investigated whether a gel spacer can enable the safe delivery of the ESTRO/ABS-recommended doses to the target while observing dose constraints for the OARs without using CS in external beam radiation therapy (EBRT). MATERIALS AND METHODS: Twenty patients who received definitive radiation therapy without CS and were treated by brachytherapy with a gel spacer between 2017 and 2022 were retrospectively reviewed. The cumulative doses of EBRT and brachytherapy treatment outcomes and incidence of adverse events were also examined. RESULTS: The median cumulative CTVHR D90%, rectum D2cm3, and bladder D2cm3 were 86.6 Gy, 62.9 Gy, and 72.0 Gy, respectively. The 2-year local control rate was 95%. There were no CTCAE ≥Grade 3 late gastrointestinal or genitourinary adverse events. CONCLUSIONS: The use of gel spacer can enable ESTRO/ABS-recommended dose constraints even without using CS in EBRT, with favorable outcomes and low adverse event rates.

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.

Cytokine release syndrome induced by immune checkpoint inhibitor treatment for uterine cervical cancer recurrence: A case report.

Cytokine release syndrome (CRS) is a systemic inflammatory condition caused by an excessive immune response and cytokine overproduction. CRS is a life-threatening condition that is often associated with chimeric antigen receptor T-cell therapy. Despite the increased use of immune checkpoint inhibitors (ICIs), ICI-induced CRS remains rare. The present study describes a case of CRS that occurred after the administration of ICIs for recurrent adenocarcinoma of the uterine cervix. A 49-year-old woman received paclitaxel, carboplatin and pembrolizumab for recurrent cervical adenocarcinoma. On day 27 of the third cycle, the patient was admitted with a fever and suspected pyelonephritis. The following day, hypotension, upper respiratory symptoms and myalgia of the extremities were noted, and the left ventricular ejection fraction (LVEF) was decreased to 20%. Multiorgan failure (MOF) occurred, and the patient received ventilator support and continuous hemodiafiltration. Rhabdomyolysis, pancreatitis, erythema multiforme and enteritis were observed. CRS was diagnosed based on elevated ferritin and IL-6 levels. Steroid pulse therapy was administered; however, the MOF did not improve and the anti-IL-6-receptor monoclonal antibody tocilizumab (TOC) was administered. Subsequently, the LVEF improved to 50%, and the patient was removed from the ventilator on day 4 and from the continuous hemodiafiltration unit on day 6 after TOC administration. The patient was discharged on day 21. In conclusion, considering that ICI-induced CRS is a rare but severe complication, fever and other systemic conditions following ICI administration should be monitored.

Carbon ion radiotherapy for mesonephric adenocarcinoma of the uterine cervix: a case report.

BACKGROUND: Mesonephric adenocarcinoma is an extremely rare subtype of uterine cervical cancer that is associated with a poor prognosis and for which a standardized treatment protocol has not been established. Carbon ion radiotherapy (CIRT) is an emerging radiotherapy modality that has been shown to have a favorable anti-tumor effect, even for tumors resistant to conventional photon radiotherapy or chemotherapy. However, there is no report on CIRT outcomes for mesonephric adenocarcinoma of the uterine cervix. CASE PRESENTATION: We treated a 47-year-old Japanese woman with mesonephric adenocarcinoma of the uterine cervix (T2bN0M0 and stage IIB according to the 7th edition of the Union for International Cancer Control and International Federation of Gynecology and Obstetrics, respectively) with CIRT combined with brachytherapy and concurrent chemotherapy. CIRT consisted of whole pelvic irradiation and boost irradiation to the gross tumor; 36.0 Gy (relative biological effectiveness [RBE]) in 12 fractions and 19.2 Gy (RBE) in 4 fractions, respectively, performed once a day, four times per week. Computed tomography-based image-guided adaptive brachytherapy was performed after completion of CIRT, for which the D90 (i.e., the dose prescribed to 90% of the target volume) for the high-risk clinical target volume was 20.4 Gy in a total of 3 sessions in 2 weeks. A weekly cisplatin (40 mg/m2) dose was administered concomitantly with the radiotherapy for a total of five courses. From 4 months post-CIRT, the patient developed metastasis of the lung, with a total of 10 lung metastases over 70 months; these lesions were treated on each occasion by photon stereotactic body radiotherapy and/or systemic therapy. At 8 years from initial treatment (i.e., 2 years after the last treatment), the patient is alive without any evidence of recurrence and maintains a high quality of life. CONCLUSIONS: This is the first report of CIRT for treatment of mesonephric adenocarcinoma of the uterine cervix. The present case indicates the potential efficacy of CIRT in combination with brachytherapy for treatment of this disease.

Acceptance, Hesitancy, and Refusal Among Parents of Young Girls in Relation to Human Papillomavirus Vaccination: A Study From the Mohammed VI University Hospital Center in Oujda, Morocco.

INTRODUCTION: Morocco has joined the global efforts to eliminate cervical cancer by introducing human papillomavirus (HPV) vaccination into its national immunization program. However, vaccination rates remain insufficient relative to the importance of the vaccine. Therefore, the objective of the study was to understand better the factors associated with acceptance, hesitance, or refusal of the HPV vaccine. MATERIALS AND METHODS: A descriptive and analytical study was conducted among 450 parents of girls of HPV vaccination age at the Mohammed VI University Hospital Center in Oujda, Morocco, over a period of three months. RESULTS: A total of 450 parents were included in the study, most of them being mothers. Most parents were unaware of HPV infection (66%) or the HPV vaccine (62%). The rate of HPV vaccination among the study population was only 33%. Factors associated with nonvaccination included a lack of information about the HPV vaccine (57%), concern about side effects (33%), and unvaccinated family and friends (10%). Parents' intention to vaccinate their daughters was significantly lower in fathers (95% confidence interval, or 95% CI = 0.34-0.66), those with a low educational level (odds ratio, or OR = 0.53; 95% CI = 0.40-0.80), and those with an unfavorable socioeconomic level (OR = 0.41; 95% CI = 0.30-0.56), whereas it was significantly higher in cases of a vaccinated entourage, including friends and family (OR = 1.52; 95% CI = 1.22-2.12), and when vaccination was recommended by a doctor (OR = 1.92; 95% CI = 1.56-2.39). CONCLUSION: The results of our study highlighted parents' lack of information about HPV infection and the HPV vaccine. They also revealed a clear lack of HPV vaccination coverage and identified the reasons for reluctance to vaccinate against HPV. Much remains to be done to increase the rate of HPV vaccination in Morocco.