Cervical cancer is a preventable disease. Nevertheless, stagnation has been seen in incidence rates also in countries with well-functioning healthcare. On this basis, we investigated associations between control interventions and changes in cervical cancer incidence in Denmark from 2009 to 2022. Data on human papillomavirus (HPV)-vaccination were retrieved from Staten\'s Serum Institute; on screening recommendations from Danish Health Authority, on screening performance from Danish Quality Database for Cervical Screening; and on cervical cancer incidence from Nordcan and Danish Cancer Register. We reported coverage with HPV vaccination (1+ dose); coverage with cervical cell samples; number of women with primary HPV tests; proportion of non-normal cell samples without timely follow-up; number of conizations; and cervical cancer incidence rates. In 2022, all women aged ≤29 had been offered childhood HPV vaccination with coverage of 80%-90%. By 2020-2022, the cervical cancer incidence rate in women aged 20-29 was 3 per 100,000; at level of disease elimination. In 2017, women aged 70+ were offered a one-time HPV screening, and by 2020-2022, the old-age peak in cervical cancer incidence had largely disappeared. From 2009 to 2022, proportion of non-normal cell samples without timely follow-up decreased from 20% to 10%, and conventional cytology was largely replaced by SurePath liquid-based cytology; these factors could explain the steady decrease in cervical cancer incidence rate. Implementation of primary HPV screening in women aged 30-59 in 2021 was reflected in a, probably temporary, increase in the 2022 cervical cancer incidence rate. In conclusion, combined interventions with childhood HPV vaccination; one-time HPV screening of elderly women; and better management of screening broke previous stagnation in cervical cancer incidence rate.

One of modern methods of estimating health losses under malignant neoplasms in economic terms, characterizing number of deaths and age of death are lost years of potential life. The cumulative losses from premature cancer mortality made up to 29 217.5 man-years in 2013 and 39 710 man-years in 2021. The number of years lost over 9 years increased by 10 492.5 man-years despite decreasing of mortality across all ages. The rate of lost years of potential life during this period increased from 5.3 to 6.2 years. The maximal contribution to lost years of potential life was made by population groups 45-59 years old. Total losses from premature mortality from cervical cancer were 2682.5 man-years and 2411 man-years in 2013 in 2021. The number of years lost decreased by 271.5 man-years. The rate of lost years of potential life during this period increased from 0.5 to 3.7 years. The greatest contribution to lost years of potential life was made by population groups 60-64 and 40-49 years old. The calculation demonstrated that there are significant reserves for reducing population mortality from malignant neoplasms in most vulnerable age population groups that is important for organization of oncological care and planning of target prevention programs.

OBJECTIVE: To determinate the association between of albumin, neutrophil-lymphocyte ratio and lymphocytes (NLR) with clinical stage in cervical cancers.
METHODS: Design a retrospective cross-sectional study of consecutive subjects diagnosed with cervical cancer for the first time. The Bethesda system was used for histological diagnosis and the subjects were stratified with the FIGO system, considering stages IA to IIB as localized; while, IIIA and IVB as advanced stages. Albumin, NLR and lymphocytes were evaluated as inflammatory biomarkers and the cut-off points generated by the ROC curves were albumin < 3 mg/dL, NLR ≥ 2.0 and lymphocytes < 1.2 103/ul. The association was calculated by Odds Ratios (OR) with 95% confidence intervals.
RESULTS: A total of 152 patients were analyzed, with mean age of 49.3 ± 14.0 years. Epidermoid cancer was the most frequent in 70.6% and 51.3% were classified as advanced clinical stages. A bivariate analysis showed significant relationships between advanced clinical stages and albumin < 3 mg/dL with OR 5.72 (CI95% 2.62-12.4; p < 0.001); for NLR ≥ 2.0 an OR 2.53 (CI95% 1.34-4.89; p = 0.005) and for lymphocytes < 1.2 103/ul of OR 3.39 (CI95% = 1.73-6.65; p < 0.001).
CONCLUSIONS: Albumin levels < 3 mg/dL, NLR ≥ 2.0 and lymphocytes < 1.2 103/ul, were associated with advanced stages in subjects with cervical cancer.

Cervical cancer remains a significant public health issue, particularly in regions with low screening uptake. This study evaluates the effectiveness of self-sampling and the 7-type HPV mRNA E6/E7 test in improving cervical cancer screening outcomes among a referral population in Mexico. A cohort of 418 Mexican women aged 25 to 65, referred for colposcopy and biopsy due to abnormal cytology results (ASC-US+), participated in this study. Self-samples were analyzed using both the 14-type HPV DNA test and the 7-type HPV mRNA E6/E7 test. The study assessed the sensitivity, specificity, positive predictive value (PPV), and the necessity of colposcopies to detect CIN3+ lesions. Participant acceptability of self-sampling was also evaluated through a questionnaire. The 7-type HPV mRNA E6/E7 test demonstrated equivalent sensitivity but significantly higher specificity (77.0%) and PPV for CIN3+ detection compared to the 14-type HPV DNA test (specificity: 45.8%, p < 0.001). The use of the HPV mRNA test as a triage tool reduced the number of colposcopies needed per CIN3+ case detected from 16.6 to 7.6 (p < 0.001). Self-sampling was highly accepted among participants, with the majority reporting confidence in performing the procedure, minimal discomfort, and willingness to undertake self-sampling at home. Self-sampling combined with the 7-type HPV mRNA E6/E7 testing offers a promising strategy to enhance cervical cancer screening by improving accessibility and ensuring precise diagnostics. Implementing these app roaches could lead to a significant reduction in cervical cancer morbidity and mortality, especially in underserved populations. Future research should focus on the long-term impact of integrating these methods into national screening programs and explore the cost-effectiveness of widespread implementation.

With one third of patients with locally advanced cervical cancer (LACC) expected to develop cancer recurrence in the first two years after therapy, accurate assessment of the response and timely detection of cancer recurrence after concurrent chemo- and radiotherapy (CCRT) treatment is of great importance. Although there is neither definite consensus about the preferred imaging modality, nor the time interval until the first diagnostic examination after CCRT, the National Comprehensive Cancer Network (NCCN) recommends the use of MRI and 18F-FDG PET/CT as a post-treatment LACC response-assessment imaging tools. In this study, we tried to appraise the early therapy response in LACC patients by both 18F-FDG PET/CT and MRI in regard to the follow-up imaging results and their mutual interrelationship, and to ascertain if the post-treatment 18F-FDG PET/CT and MRI results were related to the progression-free and overall survival rate in women with LACC after CCRT. We also aimed to estimate the early and follow-up diagnostic imaging impact on further therapy management. Based on our results, we concluded that 18F-FDG PET/CT did surpass MRI in the early assessment of therapeutic response in LACC patients after CCRT. Both modalities provided information that may serve as predictive biomarkers of outcome and LACC patients\' survival.

The tumor cells reprogram their metabolism to cover their high bioenergetic demands for maintaining uncontrolled growth. This response can be mediated by cytokines such as IL-2, which binds to its receptor and activates the JAK/STAT pathway. Some reports show a correlation between the JAK/STAT pathway and cellular metabolism, since the constitutive activation of STAT proteins promotes glycolysis through the transcriptional activation of genes related to energetic metabolism. However, the role of STAT proteins in the metabolic switch induced by cytokines in cervical cancer remains poorly understood. In this study, we analyzed the effect of IL-2 on the metabolic switch and the role of STAT5 in this response. Our results show that IL-2 induces cervical cancer cell proliferation and the tyrosine phosphorylation of STAT5. Also, it induces an increase in lactate secretion and the ratio of NAD+/NADH, which suggest a metabolic reprogramming of their metabolism. When STAT5 was silenced, the lactate secretion and the NAD+/NADH ratio decreased. Also, the expression of HIF1α and GLUT1 decreased. These results indicate that STAT5 regulates IL-2-induced cell proliferation and the metabolic shift to aerobic glycolysis by regulating genes related to energy metabolism. Our results suggest that STAT proteins modulate the metabolic switch in cervical cancer cells to attend to their high demand of energy required for cell growth and proliferation.

Background: The sentinel lymph node is the first node that cancer cells reach when migrating from the primary site. However, oncological outcomes after sentinel lymph node biopsy (SNB) have not been reported for cervical cancer. In this study, oncological outcomes were compared between patients receiving SNB and pelvic lymphadenectomy (PLD) for early-stage cervical cancer. Methods: One hundred and four patients with clinical stage 1A2, 1B1, and 2A1 cervical cancer were included in this study. All patients underwent laparoscopic or robot-assisted radical hysterectomy with SNB or PLD. Fifty-two patients with tumors ≤2 cm underwent SNB. Disease-free survival (DFS) and overall survival (OS) were compared between the groups. Results: The median (interquartile range) tumor size was 12 (7-20) mm in the SNB group and 20 (13-25) mm in the PLD group. Lymph node metastasis occurred in one patient in the SNB group and in nine patients in the PLD group. The median follow-up periods were 42 (24-60) and 82 (19-101) months in the SNB group and PLD group, respectively. The 3-year DFS rates were 100% in SNB and 91.5% in PLD. The 3-year OS was 100% in both groups. Conclusions: SNB was sufficient in cervical cancer patients with tumors ≤2 cm, suggesting that PLD might not be necessary for these patients.

Background: Patients with persistent or recurrent cervical cancer, following primary treatment with concurrent chemoradiation, represent a subgroup eligible for pelvic exenteration. In light of the substantial morbidity associated with open pelvic exenterations, minimally invasive surgical techniques have been introduced. This systematic review aims to analyze and discuss the current literature on robotic-assisted pelvic exenterations in cervical cancer. In addition, novel aspects of compartment-based magnetic resonance imaging (MRI) are highlighted. Methods: This systematic review followed the PRISMA guidelines, and a comprehensive literature search on robotic-assisted pelvic exenterations in cervical cancer was conducted to assess, as main objectives, early and late postoperative complications as well as oncological outcomes. Inclusion and exclusion criteria were applied to select eligible studies. Results: Among the reported cases of robotic-assisted pelvic exenterations in cervical cancer, 79.4% are anterior pelvic exenterations. Intraoperative complications are minimal and early/late major complications averaged between 30-35%, which is lower compared to open pelvic exenterations. Oncological outcomes are similar between robotic and open pelvic exenterations. Sensitivity for locoregional invasion increases up to 93% for compartment-based MRI in colorectal cancer. A refined delineation of the seven pelvic compartments for cervical cancer is proposed here. Conclusions: Robotic-assisted pelvic exenterations have demonstrated feasibility and safety, with reduced rates of major complications compared to open surgery, while maintaining surgical efficiency and oncological outcomes. Compartment-based MRI holds promise for standardizing the selection and categorization of pelvic exenteration procedures.

BACKGROUND: This study aimed to investigate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for primary prophylaxis of neutropenia in patients with cervical cancer receiving concurrent chemoradiotherapy.
METHODS: In this prospective, single-center, single-arm study, we enrolled patients (18-70 years) with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IIIC1r-IVA and IVB (distant metastasis only with inguinal lymph node metastasis) cervical cancer. Eligible patients should have normal function of the bone marrow (absolute neutrophil count (ANC) ≥ 2.0 × 109/L) and adequate hepatic and renal functions. Key exclusion criteria included: previous chemotherapy and/or radiotherapy; a history of bone marrow dysplasia or other hematopoietic abnormalities. All patients underwent radical radiotherapy (pelvic radiotherapy or extended-field irradiation) plus brachytherapy. The chemotherapy regimen included four cycles of 3-weekly paclitaxel and cisplatin. PEG-rhG-CSF was administered 48-72 h after each treatment cycle. Salvage granulocyte colony-stimulating factor (G-CSF) was only permitted in certain circumstances. The primary endpoint was the incidence of grade 3-4 neutropenia. The secondary endpoints included frequency of febrile neutropenia (FN), chemotherapy completion rate in cycles 2-4, time to complete radiotherapy, and safety.
RESULTS: Overall, 52 patients were enrolled in this study from July 2019 to October 2020. The incidence of grade 3-4 neutropenia was 28.8%, with an average duration of grade 3-4 neutropenia persistence of 3.85 days (1-7 days). The incidence rate of FN was 3.8%. The chemotherapy completion rate was 94.2%, 82.7%, and 75.0% for cycles 2-4, respectively. The incidences of grade 3-4 neutropenia for cycles 1-4 were 9.6% (5/52), 8.2% (4/49), 14.0% (6/43), and 2.6% (1/39), respectively. All patients completed radiotherapy within 8 weeks (median, 48 days; range: 41-56 days), except one patient who withdrew consent and did not receive radiotherapy. Severe non-hematologic toxicity was not observed in any patient.
CONCLUSIONS: PEG-rhG-CSF is an effective and safe prophylactic treatment for neutropenia in patients with cervical cancer undergoing concurrent chemoradiotherapy.
BACKGROUND: Chinese Clinical Trial Registry, ChiCTR1900024494. Date of Registration:13/July/2019.

OBJECTIVE: To assess the diagnostic potential of whole-tumor histogram analysis of multiple non-Gaussian diffusion models for differentiating cervical cancer (CC) aggressive status regarding of pathological types, differentiation degree, stage, and p16 expression.
METHODS: Patients were enrolled in this prospective single-center study from March 2022 to July 2023. Diffusion-weighted images (DWI) were obtained including 15 b-values (0 ~ 4000 s/mm2). Diffusion parameters derived from four non-Gaussian diffusion models including continuous-time random-walk (CTRW), diffusion-kurtosis imaging (DKI), fractional order calculus (FROC), and intravoxel incoherent motion (IVIM) were calculated, and their histogram features were analyzed. To select the most significant features and establish predictive models, univariate analysis and multivariate logistic regression were performed. Finally, we evaluated the diagnostic performance of our models by using receiver operating characteristic (ROC) analyses.
RESULTS: 89 women (mean age, 55 ± 11 years) with CC were enrolled in our study. The combined model, which incorporated the CTRW, DKI, FROC, and IVIM diffusion models, offered a significantly higher AUC than that from any individual models (0.836 vs. 0.664, 0.642, 0.651, 0.649, respectively; p < 0.05) in distinguishing cervical squamous cell cancer from cervical adenocarcinoma. To distinguish tumor differentiation degree, except the combined model showed a better predictive performance compared to the DKI model (AUC, 0.839 vs. 0.697, respectively; p < 0.05), no significant differences in AUCs were found among other individual models and combined model. To predict the International Federation of Gynecology and Obstetrics (FIGO) stage, only DKI and FROC model were established and there was no significant difference in predictive performance among different models. In terms of predicting p16 expression, the predictive ability of DKI model is significantly lower than that of FROC and combined model (AUC, 0.693 vs. 0.850, 0.859, respectively; p < 0.05).
CONCLUSIONS: Multiple non-Gaussian diffusion models with whole-tumor histogram analysis show great promise to assess the aggressive status of CC.