Tisotumab Vedotin as Second- or Third-Line Therapy for Recurrent Cervical Cancer.

BACKGROUND: Recurrent cervical cancer is a life-threatening disease, with limited treatment options available when disease progression occurs after first-line combination therapy. METHODS: We conducted a phase 3, multinational, open-label trial of tisotumab vedotin as second- or third-line therapy in patients with recurrent or metastatic cervical cancer. Patients were randomly assigned, in a 1:1 ratio, to receive tisotumab vedotin monotherapy (2.0 mg per kilogram of body weight every 3 weeks) or the investigator's choice of chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed). The primary end point was overall survival. RESULTS: A total of 502 patients underwent randomization (253 were assigned to the tisotumab vedotin group and 249 to the chemotherapy group); the groups were similar with respect to demographic and disease characteristics. The median overall survival was significantly longer in the tisotumab vedotin group than in the chemotherapy group (11.5 months [95% confidence interval {CI}, 9.8 to 14.9] vs. 9.5 months [95% CI, 7.9 to 10.7]), results that represented a 30% lower risk of death with tisotumab vedotin than with chemotherapy (hazard ratio, 0.70; 95% CI, 0.54 to 0.89; two-sided P = 0.004). The median progression-free survival was 4.2 months (95% CI, 4.0 to 4.4) with tisotumab vedotin and 2.9 months (95% CI, 2.6 to 3.1) with chemotherapy (hazard ratio, 0.67; 95% CI, 0.54 to 0.82; two-sided P<0.001). The confirmed objective response rate was 17.8% in the tisotumab vedotin group and 5.2% in the chemotherapy group (odds ratio, 4.0; 95% CI, 2.1 to 7.6; two-sided P<0.001). A total of 98.4% of patients in the tisotumab vedotin group and 99.2% in the chemotherapy group had at least one adverse event that occurred during the treatment period (defined as the period from day 1 of dose 1 until 30 days after the last dose); grade 3 or greater events occurred in 52.0% and 62.3%, respectively. A total of 14.8% of patients stopped tisotumab vedotin treatment because of toxic effects. CONCLUSIONS: In patients with recurrent cervical cancer, second- or third-line treatment with tisotumab vedotin resulted in significantly greater efficacy than chemotherapy. (Funded by Genmab and Seagen [acquired by Pfizer]; innovaTV 301 ClinicalTrials.gov number, NCT04697628.).

Expression patterns of mismatch repair proteins in cervical cancer uncover independent prognostic value of MSH-2.

OBJECTIVE: Although early-detected cervical cancer is associated with good survival, the prognosis for late-stage disease is poor and treatment options are sparse. Mismatch repair deficiency (MMR-D) has surfaced as a predictor of prognosis and response to immune checkpoint inhibitor(s) in several cancer types, but its value in cervical cancer remains unclear. This study aimed to define the prevalence of MMR-D in cervical cancer and assess the prognostic value of MMR protein expression. METHODS: Expression of the MMR proteins MLH-1, PMS-2, MSH-2, and MSH-6 was investigated by immunohistochemical staining in a prospectively collected cervical cancer cohort (n=508) with corresponding clinicopathological and follow-up data. Sections were scored as either loss or intact expression to define MMR-D, and by a staining index, based on staining intensity and area, evaluating the prognostic potential. RNA and whole exome sequencing data were available for 72 and 75 of the patients and were used for gene set enrichment and mutational analyses, respectively. RESULTS: Five (1%) tumors were MMR-deficient, three of which were of neuroendocrine histology. MMR status did not predict survival (HR 1.93, p=0.17). MSH-2 low (n=48) was associated with poor survival (HR 1.94, p=0.02), also when adjusting for tumor stage, tumor type, and patient age (HR 2.06, p=0.013). MSH-2 low tumors had higher tumor mutational burden (p=0.003) and higher frequency of (frameshift) mutations in the double-strand break repair gene RAD50 (p<0.01). CONCLUSION: MMR-D is rare in cervical cancer, yet low MSH-2 expression is an independent predictor of poor survival.

A phase III randomized clinical trial comparing laparoscopic radical hysterectomy based on open state with abdominal radical hysterectomy in patients with early-stage cervical cancer.

BACKGROUND: Cervical cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women, The standard treatment recommendation for women with early cervical cancer is radical hysterectomy with pelvic lymph node dissection, however, articles published in recent years have concluded that the treatment outcome of laparoscopic surgery for cervical cancer is inferior to that of open surgery. Thus, we choose a surgically new approach; the laparoscopic cervical cancer surgery in the open state is compared with the traditional open cervical cancer surgery, and we hope that patients can still have a good tumor outcome and survival outcome. This trial will investigate the effectiveness of laparoscopic cervical cancer surgery in the open-state treatment of early-stage cervical cancer. METHOD AND DESIGN: This will be an open-label, 2-armed, randomized, phase-III single-center trial of comparing laparoscopic radical hysterectomy based on open state with abdominal radical hysterectomy in patients with early-stage cervical cancer. A total of 740 participants will be randomly assigned into 2 treatment arms in a 1:1 ratio. Clinical, laboratory, ultrasound, and radiology data will be collected at baseline, and then at the study assessments and procedures performed at baseline and 1 week, 6 weeks, and 3 months, and follow-up visits begin at 3 months following surgery and continue every 3 months thereafter for the first 2 years and every 6 months until year 4.5. The primary aim is the rate of disease-free survival at 4.5 years. The secondary aims include treatment-related morbidity, costs and cost-effectiveness, patterns of recurrence, quality of life, pelvic floor function, and overall survival. CONCLUSIONS: This prospective trial aims to show the equivalence of the laparoscopic cervical cancer surgery in the open state versus the transabdominal radical hysterectomy approach for patients with early-stage cervical cancer following a 2-phase protocol. TRIAL REGISTRATION: ChiCTR2300075118. Registered on August 25, 2023.

[The lost years of potential life under cancer of neck of uterus in the Kyrgyz Republic].

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.

Exploring the prognostic significance of immunogenic cell death-related genes as risk biomarkers in cervical cancer.

BACKGROUND: Immunogenic cell death (ICD) is a process in which dying cells stimulate an immune response. It is a regulated form of cell death that can remodel the tumor microenvironment (TME) and activate the immune system, making immunotherapy more effective. This work was designed to identify prognostic gene features associated with ICD in cervical cancer (CC). METHODS: Based on CC datasets and a set of ICD-related genes obtained from public databases, we first filtered out ICD-related genes unrelated to CC survival using univariate analysis. Subsequently, LASSO regression and multivariate Cox regression analysis were employed to develop prognostic feature genes based on ICD. For the construction and validation of the model, eight genes (CXCL1, IL1B, TNF, YKT6, PDIA3, ROCK1, CXCR3, and CLEC9A) were chosen. A nomogram was created to forecast the prognosis of CC individuals, and Kaplan-Meier curves were utilized to explore the survival disparities among different risk groups of CC individuals. RESULTS: ssGSEA analysis was employed to investigate immune differences between two risk groups, revealing that the low-risk group exhibited elevated levels of immune cell infiltration, enhanced activation of immune function, and a higher immunophenoscore compared with the other group, which highlighted the relevance of ICD to TME. CONCLUSION: We constructed a prognostic model based on genetic biomarkers of ICD for prognostic prediction of CC patients. Our model demonstrated excellent discriminative and calibration capabilities, providing a valuable tool for prognostic prediction and assessing the potential efficacy of immunotherapy in CC.

Immune cell infiltration and prognostic index in cervical cancer: insights from metabolism-related differential genes.

Background: Cervical cancer remains a significant gynecologic malignancy in both China and the United States, posing a substantial threat to women's lives and health due to its high morbidity and mortality rates. Altered energy metabolism and dysregulated mitochondrial function play crucial roles in the development, growth, metastasis, and recurrence of malignant tumors. In this study, we aimed to predict prognosis and assess efficacy of anti-tumor therapy in cervical cancer patients based on differential genes associated with mitochondrial metabolism. Methods: Transcriptomic data and clinical profiles of cervical cancer patients were retrieved from the TCGA and GEO databases. Differential gene-related cellular pathways were identified through GO, KEGG, and GSEA analyses. Prognostic indices were constructed using LASSO regression analysis. Immune cell infiltration was assessed using CIBERSORT and ssGSEA, and the correlation between immune checkpoint inhibitor genes and differential genes was examined. Tumor mutation load (TMB) and its association with prognostic indices were analyzed using nucleotide variant data from the TCGA database. Patient response to immunotherapy and sensitivity to antitumor drugs were determined using the TIDE algorithm and the oncoPredic algorithm, respectively. Results: A prognostic index based on metabolism-related differential genes was developed to predict the clinical outcome of cervical cancer patients, enabling their classification into two distinct subtypes. The prognostic index emerged as an independent risk factor for unfavorable prognosis. The high-index group exhibited a significantly worse overall prognosis, along with elevated tumor mutation burden (TMB), increased immune cell infiltration, and lower TIDE scores, indicating a potential benefit from immunotherapy. Conversely, the low-index group demonstrated increased sensitivity to metabolism-related antitumor agents, specifically multikinase inhibitors. Conclusion: The aim of this study was to develop a prognostic index based on differential genes associated with mitochondrial metabolism, which could be used to predict cervical cancer patients' prognoses. When combined with TIDE and TMB analyses, this prognostic index offers insights into the immune cell infiltration landscape, as well as the potential efficacy of immunotherapy and targeted therapy. Our analysis suggests that the Iron-Sulfur Cluster Assembly Enzyme (ISCU) gene holds promise as a biomarker for cervical cancer immunotherapy.

The Role of Lymph Node Downstaging Following Neoadjuvant Treatment in a Group of Patients with Advanced Stage Cervical Cancer.

Background and Objectives: Cervical cancer is the fourth most frequent type of neoplasia in women. It is most commonly caused by the persistent infection with high-risk strands of human papillomavirus (hrHPV). Its incidence increases rapidly from age 25 when routine HPV screening starts and then decreases at the age of 45. This reflects both the diagnosis of prevalent cases at first-time screening and the likely peak of HPV exposure in early adulthood. For early stages, the treatment offers the possibility of fertility preservation.. However, in more advanced stages, the treatment is restricted to concomitant chemo-radiotherapy, combined, in very selected cases with surgical intervention. After the neoadjuvant treatment, an imagistic re-evaluation of the patients is carried out to analyze if the stage of the disease remained the same or suffered a downstaging. Lymph node downstaging following neoadjuvant treatment is regarded as an indubitable prognostic factor for predicting disease recurrence and survival in patients with advanced cervical cancer. This study aims to ascertain the important survival role of radiotherapy in the downstaging of the disease and of lymphadenectomy in the control of lymph node invasion for patients with advanced-stage cervical cancer. Material and Methods: We describe the outcome of patients with cervical cancer in stage IIIC1 FIGO treated at Bucharest Oncological Institute. All patients received radiotherapy and two-thirds received concomitant chemotherapy. A surgical intervention consisting of type C radical hysterectomy with radical pelvic lymphadenectomy was performed six to eight weeks after the end of the neoadjuvant treatment. Results: The McNemar test demonstrated the regression of lymphadenopathies after neoadjuvant treatment-p: <0.001. However, the persistence of adenopathies was not related to the dose of irradiation (p: 0.61), the number of sessions of radiotherapy (p: 0.80), or the chemotherapy (p: 0.44). Also, there were no significant differences between the adenopathies reported by imagistic methods and those identified during surgical intervention-p: 0.62. The overall survival evaluated using Kaplan-Meier curves is dependent on the post-radiotherapy FIGO stage-p: 0.002 and on the lymph node status evaluated during surgical intervention-p: 0.04. The risk factors associated with an increased risk of death were represented by a low preoperative hemoglobin level (p: 0.003) and by the advanced FIGO stage determined during surgical intervention (p-value: 0.006 for stage IIIA and 0.01 for stage IIIC1). In the multivariate Cox model, the independent predictor of survival was the preoperative hemoglobin level (p: 0.004, HR 0.535, CI: 0.347 to 0.823). Out of a total of 33 patients with neoadjuvant treatment, 22 survived until the end of the study, all 33 responded to the treatment in varying degrees, but in 3 of them, tumor cells were found in the lymph nodes during the intraoperative histopathological examination. Conclusions: For advanced cervical cancer patients, radical surgery after neoadjuvant treatment may be associated with a better survival rate. Further research is needed to identify all the causes that lead to the persistence of adenopathies in certain patients, to decrease the FIGO stage after surgical intervention, and, therefore, to lower the risk of death. Also, it is mandatory to correctly evaluate and treat the anemia, as it seems to be an independent predictor factor for mortality.

The safety and efficacy of volumetric modulated Arc therapy combined with computer tomography-guided adaptive brachytherapy for locally advanced cervical cancer: a single institution experience.

BACKGROUND: Volumetric modulated arc therapy (VMAT) is a novel form of IMRT, which can deliver more accurate dose distribution and shorten treatment time. Compared to MRI-guided adaptive brachytherapy, which is recommended as gold standard imaging for cervical cancer contours, CT-guided adaptive brachytherapy (CTGAB) is more available, more widespread, and more affordable in many centers. This study aims to retrospectively analyze the efficacy and the safety of VMAT combined with CTGAB for patients with locally advanced cervical cancer. METHODS AND MATERIALS: This study retrospectively analyzed 102 patients with locally advanced cervical cancer who underwent VMAT and CTGAB. Clinical outcomes including local control (LC), overall survival (OS) and progression-free survival (PFS), tumor response to treatment evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1), and toxicities including gastrointestinal toxicity, urinary toxicity and hematologic toxicity evaluated by the Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0) were analyzed. The Kaplan-Meier method was used to calculate LC, OS, and PFS. RESULTS: Median follow-up time was 19 months. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) occurred in 68 (66.7%), 24 (23.5%), 4 (3.92%), and 6 (5.88%), respectively. The 2-year and 3-year OS were 89.6% and 83%, respectively. The 2-year and 3-year PFS were 84.2% and 74.3%, respectively. The 2-year and 3-year LC were 90.1% and 79.3%, respectively. The average cumulative D2cm3 in the rectum, the bladder, the colon, and the small intestine were 78.07 (SD: 0.46) Gy, 93.20 (SD: 0.63) Gy, 63.55 (SD: 1.03) Gy and 61.07 (SD: 0.75) Gy, respectively. The average cumulative D90% of the high-risk clinical target volume (HR-CTV) was 92.26 (SD: 0.35) Gy. Grade ≥ 3 gastrointestinal and urinary toxicities occurred in 4.9% and 0.98%, respectively. 1.96% of patients were observed grade ≥ 4 gastrointestinal toxicities and none of the patients observed grade ≥ 4 urinary toxicities. CONCLUSION: VMAT combined with CTGAB for locally advanced cervical cancer was an effective and safe treatment method, which showed satisfactory LC, OS, PFS, and acceptable toxicities.

Impact of the universal health insurance benefits on cervical cancer mortality in Colombia.

BACKGROUND: Cervical cancer patients in Colombia have a lower likelihood of survival compared to breast cancer patients. In 1993, Colombia enrolled citizens in one of two health insurance regimes (contributory-private insurance and subsidized- public insurance) with fewer benefits in the subsidized regime. In 2008, the Constitutional Court required the Colombian government to unify services of both regimes by 2012. This study evaluated the impact of this insurance change on cervical cancer mortality before and after 2012. METHODS: We accessed 24,491 cervical cancer mortality records for 2006-2020 from the vital statistics of Colombia's National Administrative Department of Statistics (DANE). We calculated crude mortality rates by health insurance type and departments (geopolitical division). Changes by department were analyzed by rate differences between 2006 and 2012 and 2013-2020, for each health insurance type. We analyzed trends using join-point regressions by health insurance and the two time-periods. RESULTS: The contributory regime (private insurance) exhibited a significant decline in cervical cancer mortality from 2006 to 2012, characterized by a noteworthy average annual percentage change (AAPC) of -3.27% (P = 0.02; 95% CI [-5.81, -0.65]), followed by a marginal non-significant increase from 2013 to 2020 (AAPC 0.08%; P = 0.92; 95% CI [-1.63, 1.82]). In the subsidized regime (public insurance), there is a non-significant decrease in mortality between 2006 and 2012 (AAPC - 0.29%; P = 0.76; 95% CI [-2.17, 1.62]), followed by a significant increase from 2013 to 2020 (AAPC of 2.28%; P < 0.001; 95% CI [1.21, 3.36]). Examining departments from 2013 to 2020 versus 2006 to 2012, the subsidized regime showed fewer cervical cancer-related deaths in 5 out of 32 departments, while 6 departments had higher mortality. In 21 departments, mortality rates remained similar between both regimes. CONCLUSION: Improvement of health benefits of the subsidized regime did not show a positive impact on cervical cancer mortality in women enrolled in this health insurance scheme, possibly due to unresolved administrative and socioeconomic barriers that hinder access to quality cancer screening and treatment.

Prediction of outcomes after chemoradiotherapy for cervical cancer by neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio.

BACKGROUND: Cervical cancer ranks as the second most fatal tumour globally among females. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been widely applied to the diagnosis of cancers. METHODS: The clinicopathologic data of 180 patients with stage IB2-IIB cervical cancer who underwent radical concurrent chemoradiotherapy from January 2018 to December 2019 were retrospectively analysed. Receiver operating characteristic (ROC) curves were plotted to analyse the optimal cut-off values of NLR and PLR for predicting the therapeutic effects of concurrent chemoradiotherapy. The associations of PLR and other clinicopathological factors with 1-year survival rates were explored through univariate analysis and multivariate Cox regression analysis, respectively. RESULTS: NLR was significantly associated with the therapeutic effects of neoadjuvant therapy, with the optimal cut-off value of 2.89, area under the ROC curve (AUC) of 0.848 (95% confidence interval [CI]: 0.712-0.896), sensitivity of 0.892 (95% CI: 0.856-0.923) and specificity of 0.564 (95% CI: 0.512-0.592). PLR had a significant association with the therapeutic effects of neoadjuvant therapy, with the optimal cut-off value of 134.27, AUC of 0.766 (95% CI: 0.724-0.861), sensitivity of 0.874 (95% CI: 0.843-0.905) and specificity of 0.534 (95% CI: 0.512-0.556). Lymphatic metastasis ([95% CI: 1.435-5.461], [95% CI: 1.336-4.281], depth of invasion ([95% CI: 1.281-3.546], [95% CI: 1.183-3.359]) and tumour size ([95% CI: 1.129-3.451], [95% CI: 1.129-3.451]) were independent factors influencing the overall survival and disease-free survival (DFS) of patients with cervical cancer. NLR (95%CI: 1.256-4.039) and PLR (95%CI:1.281-3.546) were also independent factors affecting DFS. CONCLUSION: NLR and PLR in the peripheral blood before treatment may predict DFS of patients with stage IB2-IIB cervical cancer.

The clinicopathologic data of 180 patients with stage IB2-IIB cervical cancer who underwent radical concurrent chemoradiotherapy were retrospectively analysed. Receiver operating characteristic curves showed that neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were significantly associated with the therapeutic effects of neoadjuvant therapy. Univariate and multivariate regression analysis revealed that lymphatic metastasis, depth of invasion and tumour size were independent factors influencing the overall survival and disease-free survival (DFS) of patients with cervical cancer. NLR and PLR in the peripheral blood before treatment may predict the DFS of patients with stage IB2-IIB cervical cancer.

The complement regulatory protein CD46 serves as a novel biomarker for cervical cancer diagnosis and prognosis evaluation.

Background: CD46 has been revealed to be a key factor in malignant transformation and cancer treatment. However, the clinical significance of CD46 in cervical cancer remains unclear, and this study aimed to evaluate its role in cervical cancer diagnosis and prognosis evaluation. Methods: A total of 180 patients with an initial diagnosis of cervical cancer were enrolled at Taizhou Hospital of Zhejiang Province, China. The plasma levels of soluble CD46 (sCD46) and the expression of membrane-bound CD46 (mCD46) were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC), respectively. Results: CD46 was found to be significantly upregulated in cervical cancer tissues vs. normal tissues, while no CD46 staining was detected in paired adjacent noncancerous tissues. CD46 staining was more pronounced in cancer cells than in stromal cells in situ (in tissues). Moreover, the plasma levels of sCD46 were able to some extent discriminate between cancer patients and healthy women (AUC=0.6847, 95% CI:0.6152-0.7541). Analysis of Kaplan-Meier survival curves revealed that patients with low CD46 expression had slightly longer overall survival (OS) than patients with high CD46 expression in the tumor microenvironment, but no significant difference. Univariate Cox regression analysis revealed that CD46 (P=0.034) is an independent risk factor for OS in cervical cancer patients. Conclusion: The present study demonstrated that cervical cancer patients exhibit aberrant expression of CD46, which is closely associated with a poor prognosis, suggesting that CD46 plays a key role in promoting cervical carcinogenesis and that CD46 could serve as a promising potential target for precision therapy for cervical cancer.

Cervical cancer trend in the Republic of Kazakhstan and attitudes towards cervical cancer screening in urban and rural areas.

Cervical cancer (CC) continues to be a significant global health issue, which in part can be attributed to disparities in access to CC screening services. This study aims to conduct a trend of CC in Kazakhstan and to compare attitudes towards the screening program between women living in urban and rural areas. In the first stage, we conducted a trend study of CC indicators in Kazakhstan using official statistics. In the second stage, a cross-sectional study was conducted using a structured questionnaire to assess adherence to screening. The trend study reveals a decline in cervical cancer mortality rates (from 7.15 to 5.93 per 100,000 female inhabitants) over the period studied, while the incidence remains stable (from 18.51 to 19.38 per 100,000 female inhabitants). Regional variations in Period Prevalence rates were observed. Significant differences were found in screening participation rates between urban n = 41 (74%) and rural n = 23 (38%) women, p < 0.001, as well as awareness of the screening program (urban: n = 15 (27%), rural: n = 35 (58%), p < 0.001). The trend study highlights a decrease in cervical cancer mortality rates over the specified period, accompanied by a consistent incidence rate. Additionally, regional disparities in period prevalence rates of cervical cancer were observed. The primary factor contributing to the low adherence of rural women to screening was found to be a lack of awareness regarding the screening program. Therefore, increasing awareness about the importance of screening is crucial for improving adherence rates among rural women in Kazakhstan.

125I seed brachytherapy for non-central pelvic recurrence of cervical cancer after external beam radiotherapy.

OBJECTIVE: To investigate the efficacy of 125I seed brachytherapy for non-central pelvic recurrence of cervical cancer after external beam radiotherapy, and to analyze the clinical influential factors. METHODS: Between June 2015 and April 2022, 32 patients with 41 lesions were treated with 125I seed brachytherapy. The seeds were implanted under the guidance of CT and/or 3D-printed template images at a median dose of 100 Gy (range, 80-120 Gy), and the local control rate (LCR) and survival rates were calculated. We used multivariate logistic regression to identify prognosis predictors, and receiver operating characteristic (ROC) curve analysis to determine the optimal cut-off values. RESULTS: The median follow-up was 48.52 months (range, 4-86 months), and the 6-, 12-, and 24-month LCR was 88.0%, 63.2%, and 42.1%, respectively. The 1- and 2-year survival rates were 36% and 33%, respectively, and the median survival time was 13.26 months. No significant adverse events occurred. Multivariate regression analysis showed that tumor diameter, tumor stage, and LCR were independent factors influencing survival. ROC curve analysis showed that the area under the curve for tumor diameter and D90 were 0.765 and 0.542, respectively, with cut-off values of 5.3 cm and 108.5 Gy. CONCLUSIONS: The present findings indicate that 125I seed brachytherapy is feasible for treating non-central pelvic recurrence of cervical cancer after external beam radiotherapy. Further, tumor diameter < 5.3 cm and immediate postoperative D90 > 108.5 Gy were associated with better efficacy.

Productivity costs due to human papillomavirus-related cancer mortality in the United Kingdom.

BACKGROUND: Human papillomavirus (HPV) causes several cancers such as cervical cancer and some head and neck (oral cavity, pharynx, and larynx), vulval, vaginal, anal, and penile cancers. As HPV vaccination is available, there is potential to prevent these cancers attributed to HPV and consequently the burden associated with them. The aim of this analysis was to estimate the number of HPV-related cancer deaths and the productivity costs due to years of life lost (YLL) in the United Kingdom (UK). METHOD: A model was developed utilizing UK 2019 mortality data sourced from country-specific databases for England, Scotland, Wales, and Northern Ireland for the following HPV-related cancers: head and neck (ICD-10 C00-14 and C32), cervix uteri (C53), vaginal (C51), vulval (C52), anal (C21), and penile (C60). The proportion of deaths and years of life lost (YLL) due to HPV were estimated using HPV attributable fractions for each anatomic location from the published literature. Labor force participation, retirement ages, and mean annual earnings, discounted at 3.5% annually, were applied to YLL to calculate the present value of future lost productivity (PVFLP). RESULTS: A total of 1817 deaths due to HPV-related cancers were reported in the UK in 2019 resulting in 31,804 YLL. Restricting to only YLL that occurred prior to retirement age yielded a total YPLL of 11,765 and a total PVFLP of £187,764,978. CONCLUSIONS: There is a high disease burden in the UK for HPV-related cancers, with a large economic impact on the wider economy due to productivity losses. Implementing and reinforcing public health measures to maintain high HPV vaccination coverage in both males and females may further facilitate reduction of this burden.

Nab-paclitaxel plus platinum versus paclitaxel plus platinum as first-line therapy in patients with metastatic or recurrent cervical cancer.

PURPOSE: This study aimed to assess the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus platinum versus paclitaxel plus platinum as first-line therapy in patients with metastatic or recurrent cervical cancer. METHODS: Between October 2020 and March 2022, consecutive patients with diagnosed with metastatic or recurrent cervical cancer were retrospectively recruited in our hospital. Fifty-four patients were treated with nab-paclitaxel plus cisplatin or carboplatin. Twenty-four patients were treated with paclitaxel plus cisplatin or carboplatin. A propensity score matching (PSM) analysis was done using a multivariable logistic regression model. The two groups were compared for objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in the raw and matched dataset. RESULTS: The nab-paclitaxel group showed a higher ORR than the paclitaxel group both in the raw dataset (72.2% vs. 45.8%; P = 0.025) and matched dataset (81.1% vs. 47.6%; P = 0.008). The median PFS was significantly longer in the nab-paclitaxel group than in the paclitaxel group both in the raw and matched dataset (12 vs. 7 months; P < 0.05). The median OS was not reached in the nab-paclitaxel group compared with 15 months in the paclitaxel group, with a trend toward prolongation. The most common toxicity was hematological adverse events, including grade 3-4 neutropenia, grade 3 anemia and thrombocytopenia in both groups and no statistical differences were observed between the groups (all P > 0.05). CONCLUSION: Compared with paclitaxel plus platinum, nab-paclitaxel plus platinum may be an effective and tolerable option as first-line therapy for patients with metastatic or recurrent cervical cancer.

Development and validation of nomograms to predict survival of primary cervical lymphoma: A surveillance, epidemiology, and end results (SEER) database analysis.

Due to the rarity of primary cervical lymphoma (PCL), the long-term survival of patients with cervical lymphoma and factors influencing survival are unknown. This study aimed to compare the survivals of patients with PCL and those with other cervical tumors and construct a clinical prediction model to assess the prognosis of patients with PCL. Patients with PCL from the Surveillance, Epidemiology, and End Results database were allocated randomly in a 7:3 ratio to the training and validation sets. Cox proportional hazard and Fine-Gray models were used to verify independent factors influencing overall survival (OS) and disease-specific survival (DSS), and nomograms were constructed. Receiver operating characteristic curve analysis and decision curve analysis (DCA) were used to test the performance and clinical utility of the models, respectively. We included 206 patients with PCL. The areas under the curves (AUCs) and DCA showed that all models had clinical benefits; The models constructed in this study had a predictive performance for patients with PCL. It can guide clinicians to rationalize the treatment plan for patients.

Cervical cancer-specific long non-coding RNA landscape reveals the favorable prognosis predictive performance of an ion-channel-related signature model.

BACKGROUND: Ion channels play an important role in tumorigenesis and progression of cervical cancer. Multiple long non-coding RNA genes are widely involved in ion channel-related signaling regulation. However, the association and potential clinical application of lncRNAs in the prognosis of cervical cancer are still poorly explored. METHODS: Thirteen patients with cervical cancer were enrolled in current study. Whole transcriptome (involving both mRNAs and lncRNAs) sequencing was performed on fresh tumor and adjacent normal tissues that were surgically resected from patients. A comprehensive cervical cancer-specific lncRNA landscape was obtained by our custom pipeline. Then, a prognostic scoring model of ion-channel-related lncRNAs was established by regression algorithms. The performance of the predictive model as well as its association with the clinical characteristics and tumor microenvironment (TME) status were further evaluated. RESULTS: To comprehensively identify cervical cancer-specific lncRNAs, we sequenced 26 samples of cervical cancer patients and integrated the transcriptomic results. We built a custom analysis pipeline to improve the accuracy of lncRNA identification and functional annotation and obtained 18,482 novel lncRNAs in cervical cancer. Then, 159 ion channel- and tumorigenesis-related (ICTR-) lncRNAs were identified. Based on nine ICTR-lncRNAs, we also established a prognostic scoring model and validated its accuracy and robustness in assessing the prognosis of patients with cervical cancer. Besides, the TME was characterized, and we found that B cells, activated CD8+ T, and tertiary lymphoid structures were significantly associated with ICTR-lncRNAs signature scores. CONCLUSION: We provided a thorough landscape of cervical cancer-specific lncRNAs. Through integrative analyses, we identified ion-channel-related lncRNAs and established a predictive model for assessing the prognosis of patients with cervical cancer. Meanwhile, we characterized its association with TME status. This study improved our knowledge of the prominent roles of lncRNAs in regulating ion channel in cervical cancer.

Survival status and predictors of mortality among cervical cancer patients at oncologic centers in Addis Ababa, Ethiopia: a follow up study.

BACKGROUND: Cervical cancer (CC) ranks as the third most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths among women globally. In Addis Ababa, there is a shortage of available evidence concerning the phenomenon of survival time and its predictors among women diagnosed with CC. Therefore, this study aimed to assess the survival status and predictors of mortality among CC patients at oncologic centers in Addis Ababa, Ethiopia. METHODS: A facility-based retrospective cohort study was conducted among records of women with cervical cancer enrolled from the 1st of January 2017 to the 30th of December 2022 among 252 cervical cancer patients. Data were collected using a pretested, structured data collection checklist by trained data collectors. The Kaplan-Meier survival curve was used to estimate the survival time of the respondents. The Cox multivariable regression model was carried out to identify predictors of CC. Variables with P-value < 0.05 in multivariable analysis were declared as statistically significant. RESULTS: The cumulative proportion of surviving at the end of the 10th and 20th month was 99.6% (95%CI: 97.02, 99.94) and 96.99% (95%CI: 93.41, 98.64), respectively. Similarly, it was 92.67% (95%CI: 87.65, 95.70), 85.9% (95%CI: 78.68, 90.94), 68.0% (95%CI: 57.14, 76.66) and 18.27% (8.38, 31.16) at the end of 30th, 40th, 50th and 60th monthly respectively. The overall median survival time was 54 months (95%CI: 52.6, 55.4). The incidence of death among a cohort of women with CC was 7.34 per 1000 person months. Being anemic (AHR: 4.77; 95%CI: 1.93, 11.77; P-value: 0.001), took a single cancer treatment (AHR: 1.92; 95%CI: 1.01, 3.64; P-value: 0.046) and HIV sero status positive (AHR: 2.05; 95%CI: 1.01, 4.19; P-value: 0.048) were statistically significant in multivariable cox proportional hazard model. CONCLUSION AND RECOMMENDATION: Anemia, treatment initiation and HIV-sero status were independent predictors of mortality among women admitted with CC. It is imperative to enhance early screening initiatives and treatment resources for CC, alongside fostering public awareness through collaboration with various media outlets concerning preventive measures, screening procedures, and treatment alternatives for CC.

Impact of CD44 genetic variants on clinicopathological characteristics of uterine cervical cancer patients.

CD44 genetic variants have been found to be related to various cancers. However, to date, no study has demonstrated the involvement of CD44 polymorphisms in uterine cervical cancer in Taiwanese women. Therefore, we conducted a retrospective study, consecutively recruiting 113 patients with invasive cancer, 92 patients with high-grade cervical intraepithelial neoplasias, and 302 control women to assess the relationships among CD44 polymorphisms, cervical carcinogenesis, and patient survival. Real-time polymerase chain reaction was used to determine the genotypic distributions of six polymorphisms: rs1425802, rs187115, rs713330, rs11821102, rs10836347, and rs13347. The results revealed that women with the mutant homozygous genotype CC exhibited a higher risk of invasive cancer compared to those with the wild homozygous genotype TT [p=0.035; hazard ratio (HR)=10.29, 95% confidence interval (95% CI)=1.18-89.40] and TT/TC [p=0.032; HR=10.66, 95% CI=1.23-92.11] in the CD44 polymorphism rs713330. No significant association was found between CD44 genetic variants and clinicopathological parameters. Among the clinicopathological parameters, only positive pelvic lymph node metastasis (p=0.002; HR=8.57, 95% CI=2.14-34.38) and the AG/GG genotype compared to AA (p=0.014; HR=3.30, 95% CI=1.28-8.49) in CD44 polymorphism rs187115 predicted a higher risk of poor five-year survival, according to multivariate analysis. In conclusion, an important and novel finding revealed that Taiwanese women with the AG/GG genotype in CD44 polymorphism rs187115 exhibited a higher risk of poor five-year survival.