Implementation of WHO guidelines for cervical cancer screening, diagnosis and treatment: knowledge and perceptions of health providers from Argentina.

BACKGROUND: The 2021 World Health Organization (WHO) guidelines on cervical cancer screening and treatment provide countries with evidence-based recommendations to accelerate disease elimination. However, evidence shows that health providers' adherence to screening guidelines is low. We conducted a study in Argentina to analyze health providers' knowledge and perceptions regarding the 2021 WHO Guidelines. METHODS: A qualitative study was conducted based on individual, semi-structured interviews with health providers specializing in gynecology (n = 15). The themes explored were selected and analyzed using domains and constructs of the Consolidated Framework for Implementation Research. RESULTS: Although health providers perceive WHO as a reliable institution, they do not know the 2021 guidelines, its supporting evidence, and its elaboration process. Their clinical practice is mainly guided by local recommendations developed by national professional medical associations (PMAs). For interviewees, WHO guidelines should be disseminated through health authorities and national PMAs, mainly through in-service training. Health providers had a positive assessment regarding WHO Recommendation 1 (screen, triage, and treatment for women aged 30 + with HPV-testing every 5 to 10 years) and perceived a favorable climate for its implementation. HPV-testing followed by triage was considered a low-complexity practice, enabling a better detection of HPV, a better selection of the patients who will need diagnosis and treatment, and a more efficient use of health system resources. However, they suggested adapting this recommendation by removing screening interval beyond 5 years. WHO Recommendation 2 (screen-and-treat approach with HPV-testing for women aged 30 + every 5 to 10 years) was predominantly rejected by interviewees, was considered an algorithm that did not respond to women's needs, and was not adequate for the Argentinean context. Regarding the HPV-test modality, clinician-collected tests were the preferred mode. Health providers considered that HPV self-collection should be used primarily among socially vulnerable women to increase screening coverage. CONCLUSION: WHO guidelines should be widely disseminated among health providers, especially in settings that could benefit from a screen-and-treat approach. Identifying areas of partnership and collaboration with PMAs in implementing WHO guidelines is essential.

Promising predictive molecular biomarkers for cervical cancer (Review).

Cervical cancer (CC) constitutes a serious public health problem. Vaccination and screening programs have notably reduced the incidence of CC worldwide by >80%; however, the mortality rate in low­income countries remains high. The staging of CC is a determining factor in therapeutic strategies: The clinical management of early stages of CC includes surgery and/or radiotherapy, whereas radiotherapy and/or concurrent chemotherapy are the recommended therapeutic strategies for locally advanced CC. The histopathological characteristics of tumors can effectively serve as prognostic markers of radiotherapy response; however, the efficacy rate of radiotherapy may significantly differ among cancer patients. Failure of radiotherapy is commonly associated with a higher risk of recurrence, persistence and metastasis; therefore, radioresistance remains the most important and unresolved clinical problem. This condition highlights the importance of precision medicine in searching for possible predictive biomarkers to timely identify patients at risk of treatment response failure and provide tailored therapeutic strategies according to genetic and epigenetic characteristics. The present review aimed to summarize the evidence that supports the role of several proteins, methylation markers and non­coding RNAs as potential predictive biomarkers for CC.

[Effect of COVID-19 pandemics in treatment of cervical cancer: pre/post study]. / Efecto de COVID-19 en el tratamiento del cáncer cervicouterino: estudio antes/después.

INTRODUCTION: Little evidence exists on the impact of the COVID-19 pandemics on the compliance with cervical cancer treatment. METHODS: We carried out a population-based, before-and-after retrospective cohort study of all cervical cancer patients diagnosed in the Jujuy province public health sector (n=140), Argentina, between 2017 and 2020. Patients diagnosed in 2020 were considered exposed to the COVID-19 pandemic (n=21). We used multivariable logistic regression to assess the relationship between the pandemics and compliance with treatment. We also measured treatment duration for women who were indicated brachytherapy and time to treatment initiation by stage. RESULTS: Compared with women diagnosed in 2017-2019 the odds ratio of non-complying with treatment was 1.77 (95%CI 0.59-5.81; p = 0.32) for women diagnosed during 2020. An increased risk of non-compliance was found in patients with prescribed brachytherapy (OR 4.14. 95%CI 1.95-9.11; p < 0.001). Median treatment duration for women with prescribed brachytherapy was 12.8 and 15.7 weeks in 2017-2019 vs. 2020 (p = 0.33); median time to treatment initiation for women with early-stage disease was 9 and 5 weeks during 2017-2019 and 2020 respectively (p = 0.06), vs 7.2 and 9 weeks in 2017-2019 and 2020 respectively (p = 0.36) for patients with stages IIB+ disease. CONCLUSIONS: Low access to brachytherapy was a major determinant of non-compliance. irrespective of the effect of the pandemics.

Introducción: Hay escasa evidencia sobre el impacto de la pandemia de COVID-19 en el cumplimiento del tratamiento de cáncer cervicouterino. Métodos: Se llevó a cabo un estudio poblacional de cohorte retrospectivo. ­antes/después­ de las pacientes con cáncer cervicouterino diagnosticadas en establecimientos públicos de la provincia de Jujuy (n = 140), entre 2017 y 2020. Las pacientes diagnosticadas en 2020 se consideraron expuestas a la pandemia (n = 21). Utilizamos la regresión logística multivariada para analizar la asociación entre pandemia y cumplimiento del tratamiento de cáncer. Además, se midió la duración del tratamiento en aquellas con indicación de braquiterapia y el tiempo hasta el inicio al tratamiento según estadio. Resultados: Comparadas con las mujeres diagnosticadas en 2017-2019 el odds ratio de incumplimiento del tratamiento fue de 1.77 (IC95% 0.59-5.81; p = 0.32) para las diagnosticadas durante 2020. Se encontró un mayor riesgo de incumplimiento en pacientes con indicación de braquiterapia (OR 4.14; IC 95%:1.95-9.11; p < 0.001). La mediana de duración del tratamiento para aquellas con indicación de braquiterapia fue de 12.8 y 15.7 semanas en 2017-2019 y 2020 respectivamente (p = 0.33). La mediana de tiempo hasta el inicio del tratamiento para pacientes con enfermedad en estadio temprano fue de 9 y 5 semanas durante 2017-2019 y 2020 respectivamente (p = 0.06), versus una mediana de 7.2 y 9 semanas en 2017-2019 y 2020 respectivamente (p=0.36) para las pacientes con enfermedad en estadio IIB+. Conclusiones: El bajo acceso a la braquiterapia fue un factor determinante de incumplimiento de tratamiento de cáncer cervicouterino, independientemente del efecto de la pandemia.

Sociodemographic characteristics and their association with survival in women with cervical cancer.

BACKGROUND: In 2020, the highest incidence and mortality from cervical cancer (CC) were detected in low and middle-income countries. CC remains a health problem for women living in them. In Mexico, CC ranks second in cancer incidence and mortality in women. The main characteristics of this population are low income, low educational level, and inadequate medical coverage. The present study characterized the Mexican population by CC, and the sociodemographic variables that impacted overall survival (OS) were identified. METHODS: A retrospective study that included a cohort of patients with a confirmed diagnosis of CC at the Instituto Nacional de Cancerologia between 2003 and 2016. Information was collected on sociodemographic variables related to the disease and OS. RESULTS: Four thousand six hundred thirty-one patients were included. The median age was 51 years, 78.5% were unemployed, 44.4% lived in a rural/suburban area, 50.8% had a partner when collecting this information, and 74.3% were classified as having low socioeconomic status. Age, living in a rural/suburban area, more advanced stages of the disease, and not receiving cancer treatment were associated with lower OS. CONCLUSION: CC continues to affect mainly women with minimal resources, low educational levels, and living in marginalized areas. These characteristics influence the OS. Prevention and timely detection programs, education, and training focused on this population and with broader coverage are required to identify patients with CC at earlier stages.

Linking tumor immune infiltrate and systemic immune mediators to treatment response and prognosis in advanced cervical cancer.

Cervical cancer (CC) poses a significant burden on individuals in developing regions, exhibiting heterogeneous responses to standard chemoradiation therapy, and contributing to substantial mortality rates. Unraveling host immune dynamics holds promise for innovative therapies and discovery of clinically relevant biomarkers. We studied prospectively locally advanced CC patients pre-treatment, stratifying them as responders (R) or non-responders (NR). R patients had increased tumor-infiltrating lymphocytes (TILs), while NR patients showed elevated PD-1 scores, CD8+ and PD-L2+ TILs, and PD-L1 immune reactivity. NR patients exhibited higher systemic soluble mediators correlating with TIL immune markers. R patients demonstrated functional polarization of CD4 T cells (Th1, Th2, Th17, and Treg), while CD8+ T cells and CD68+ macrophages predominated in the NR group. Receiver operating characteristic analysis identified potential CC response predictors, including PD-L1-immunoreactive (IR) area, PD-L2, CD8, FGF-basic, IL-7, IL-8, IL-12p40, IL-15, and TNF-alpha. Dysfunctional TILs and imbalanced immune mediators contribute to therapeutic insufficiency, shedding light on local and systemic immune interplay. Our study informs immunological signatures for treatment prediction and CC prognosis.

The Cervical Cancer Treatment Gap in Mexico Under Seguro Popular, 2006-2016.

From 2005 to 2019, the Mexican government financed cervical cancer treatment for individuals without social security insurance through Seguro Popular's Fund for Protection against Catastrophic Health Expenses. To better understand the impact of this program on access to treatment, we estimated the cervical cancer treatment gap (the proportion of patients with cervical cancer in this population who did not receive treatment). To calculate the expected number of incident cervical cancer cases we used national surveys with information on insurance affiliation and incidence estimates from the Global Burden of Disease study. We used a national claims database to determine the number of cases whose treatment was financed by Seguro Popular. From 2006 to 2016, the national cervical cancer treatment gap changed from 0.61 (95% CI 0.59 to 0.62) to 0.45 (95% CI 0.43 to 0.48), with an average yearly reduction of -0.012 (95% CI -0.024 to -0.001). The gap was greater in states with higher levels of marginalization and in the youngest and oldest age groups. Although the cervical cancer treatment gap among individuals eligible for Seguro Popular decreased after the introduction of public financing for treatment, it remained high. Seguro Popular was eliminated in 2019; however, individuals without social security have continued to receive cancer care financed by the government in the same healthcare facilities. These results suggest that barriers to care persisted after the introduction of public financing for treatment. These barriers must be reduced to improve cervical cancer care in Mexico, particularly in states with high levels of marginalization.

Effect of guided imagery relaxation on anxiety in cervical cancer: randomized clinical trial.

OBJECTIVES: to evaluate the effect of guided imagery relaxation through virtual reality on anxiety in women with cervical cancer undergoing radiochemotherapy. METHODS: randomized, non-blinded, single-center clinical trial conducted at a cancer reference hospital. 52 women participated, with randomized allocation of 24 in the control group and 28 in the experimental group (12 sessions of guided imagery relaxation through virtual reality, applied three times a week). The outcome was evaluated using the State-Trait Anxiety Inventory and statistical analysis was performed using the Generalized Linear Mixed Model. RESULTS: n the experimental group, women presented significant anxiety traits (p=0.010) before the intervention. Between the 4th and 12th week of follow-up, there was a reduction in anxiety levels, without statistical significance. CONCLUSIONS: guided imagery relaxation through virtual reality provided evidence of anxiety reduction in women with cervical cancer undergoing radiochemotherapy and may contribute to clinical practice. Brazilian Clinical Trial Registry: RBR-7ssvytb.

Comparison of clinical outcomes among cancer patients treated in and out of clinical trials.

BACKGROUND: It is unknown if participation in a cancer clinical trial confers clinical benefits to patients. There is not enough scientific evidence in this regard and the available publications are scarce and provide ambiguous and limited information. OBJECTIVE: Compare overall and progression-free survival and response to treatment among those who met the eligibility criteria and accepted to participate and those who refused to participate in cancer clinical trials. METHODS: An observational cross-sectional study with an analytical component was carried out, which included patients diagnosed with cancer who participated in phase III clinical trials and patients who, being eligible, refused to participate. The patients were cared for at the National Institute of Cancerology in Colombia between 2019 and 2022. Analysis of differences in proportions and means of sociodemographic and clinical variables was included; overall survival and progression-free survival time were described and the survival curves between groups were compared. Variables related to survival were determined using a Cox regression model and Hazard Ratios were calculated. RESULTS: 62 women and 50 men were included. In the women group, we found a statistical association between clinical trial participation and non-serious events adverse and progression. The stable disease and complete response were higher in participants than in refusers. The median progression-free survival for refusers was 7,4 m meantime for participants the median was not reached and 74,1% remained without progression at 28 months. In the men group, we also found a statistical association between clinical trial participation and the occurrence of non-serious events adverse meanwhile there were no significant differences in overall response, progression, and death, even though the proportion of progression was minor in participants 20% vs. refusers 26% respectively. The median survival was not reached for any group, even though in the participants group 55,2% were still alive at month 20 and in the refusers group still alive at 56,8% at month 45. Covariables included for the multivariate Cox regression only age had a statistical association with overall survival in the women's group and the men group any covariables reached statistical association. CONCLUSION: It can be considered that participation in clinical trials could give participants a better response to treatment, without increasing the probability of death and with the probability of decreasing the progression of the disease. Participation in trials could improve the outcomes of clinical response rates, no change in overall survival, and progression-free.

Insurance status and access to cervical cancer treatment in a specialized cancer center in Mexico.

To describe access to complete treatment in women with cervical cancer and state-sponsored insurance versus no insurance. We conducted a retrospective observational study. The source population consisted of women treated for cervical cancer from January 2000 to December 2015 in a tertiary care hospital. We included 411 women with state-sponsored insurance and 400 without insurance. We defined access to cervical cancer treatment as complete treatment (according NCCN/ESMO (National Comprehensive Cancer Network/European Society for Medical Oncology) standards) and timely initiation of treatment (less than 4 weeks). Clinical and sociodemographic characteristics were described and analyzed with logistic regression using complete treatment as the main outcome. A total of 811 subjects were included, the median age was 46 (IQR (Interquartile range) 42-50) years. Most of them were married (36.1%), unemployed (50.4%), and had completed primary school (44.0%). The most common clinical stages at diagnosis were II (38.2%) and III (24.7%). In the adjusted regression model, being married (OR (odds ratio): 4.3, 95% CI (confidence interval): 1.74-10.61) and having paid employment (OR: 2.79, 95% CI: 1.59-4.90) or state-sponsored insurance (OR: 1.54, 95% CI: 1.04-2.26) were positively associated with the possibility of having a complete treatment. Women with insurance were likely to be younger and receive timely treatment compared with uninsured women. Complete treatment was associated to insurance status and advanced stages of cervical cancer. State-sponsored insurance improves access to complete treatment. Government policies are needed to avoid social and economic inequity and provide better management of cervical cancer in our country.

The role of daughters in relation to their mother's cervical cancer diagnosis and treatment in Guatemala: a descriptive study.

PURPOSE: There is currently no information on how caregivers for women diagnosed with cervical cancer in Guatemala, particularly daughters, are affected by their supportive role. This study's objective was to describe the support role of caregivers in the country, with a focus on daughters with a mother diagnosed with cervical cancer. METHODS: This analysis utilizes data from a cross-sectional study which aimed to understand pathways to cervical cancer care. Women seeking cervical cancer treatment at the Instituto de Cancerologia (INCAN) in Guatemala City, Guatemala and their companions were surveyed. Descriptive statistics were calculated. RESULTS: One hundred forty-five women seeking treatment and 71 companions participated in the study. Patient's daughters were most frequently reported as the person who provided the most support (51%) and as the most reported to have encouraged the patient to seek care. Furthermore, daughters were noted as the person most reported to fulfill the major household and livelihood roles of the patient while they were seeking or receiving treatment (38.0%). Most daughters reported that they were missing housework (77%), childcare (63%), and income-earning activities (60%) to attend the appointment with their mothers. CONCLUSION: Our study suggests that in Guatemala cervical cancer patient's daughters have a significant support role in their mother's cancer diagnosis. Furthermore, we found that while caring for their mothers, daughters in Guatemala are often unable to participate in their primary labor activities. This highlights the additional burden that cervical cancer has on women in Latin America.

Experiences of women with advanced cervical cancer before starting the treatment: Systematic review of qualitative studies.

BACKGROUND: Advanced stage and high mortality are characteristics of cervical cancer in developing countries. Comprehension of the diagnosis itinerary is one of the main strategies to control the disease impact. OBJECTIVES: To identify reasons for the delay in diagnosing symptomatic cervical cancer according to the patient's perspectives reported in qualitative studies. We searched four databases (PubMed, Embase, CINAHL, and Web of Science). SELECTION CRITERIA: We included qualitative studies of women with advanced cervical cancer that explored their experiences before treatment. We excluded unoriginal, non-qualitative, and duplicated studies. DATA COLLECTION AND ANALYSIS: We selected 39 articles for a full-text reading and included 15 in the present review. We chose the Consolidated Criteria for Reporting Qualitative Research (COREQ) for quality assessment and The Model of Pathways to Treatment to guide the codifying process. MAIN RESULTS: Four main themes emerged from the synthesis: (1) Health-seeking motivators; (2) Obstacles to seeking medical care; (3) Diagnosis delay; and (4) Coping with the disease. These themes were derived from patients' personal knowledge and beliefs, social relationships, socioeconomic status, and healthcare system characteristics. CONCLUSIONS: Individual behavior, social factors, and healthcare organization contribute to the delay in diagnosing advanced cervical cancer.

Disparities in Diagnosis and Treatment of Cervical Adenocarcinoma Compared With Squamous Cell Carcinoma: An Analysis of the National Cancer Database, 2004-2017.

OBJECTIVES: The aim of the study are to compare trends in diagnosis and treatment of adenocarcinoma of the cervix (AC) to squamous cell carcinoma of the cervix (SCC) and to examine associations between stage at diagnosis and guideline-concordant treatment with race, age, and insurance type for AC and SCC. MATERIALS AND METHODS: We performed a retrospective cohort study of cervical AC ( n = 18,811) and SCC ( n = 68,421) from the 2004-2017 National Cancer Database. We used generalized linear models to evaluate trends in frequency of histologies and to evaluate associations between race, age, and insurance status with stage of diagnosis and receipt of National Comprehensive Cancer Network guideline-concordant treatment for AC and SCC. RESULTS: The proportion of AC relative to SCC increased from 19.4% (95% CI = 18.4-20.5) to 23.2% (95% CI = 22.2-24.2) from 2004 to 2017 ( p < .001). Compared with SCC, women with AC were younger, more likely to be White, and privately insured ( p < .001). Older women with AC were 44% less likely to be diagnosed with early-stage disease than younger women (adjusted relative risk = 0.56, 95% CI = 0.52-0.60); there was no significant difference for SCC. Black women with AC were 16% less likely to be diagnosed with early-stage disease (adjusted relative risk [aRR] = 0.84, 95% CI = 0.79-0.89) than White women. Women with public insurance were less likely to be diagnosed at an early stage for both AC (aRR = 0.81, 95% CI = 0.78-0.84) and SCC (aRR = 0.79, 95% CI = 0.77-0.81). Rates of guideline-concordant treatment were similar for AC and SCC, with minimal differences by age, race, and insurance. CONCLUSIONS: As the proportion of AC to SCC rises, important race and age-related disparities must be addressed to reduce unnecessary morbidity and death.

Effectiveness of cryotherapy delivered by nurses for treatment of cervical preneoplasic lesions / Efectividad de la crioterapia suministrada por enfermeras para lesiones preneoplásicas del cuello uterino.

Introduction. Cervical cancer is a relevant public health problem for low- and middleincome countries. Follow-up of positive-screened women and compliance with treatment of precancerous lesions are major challenges for these settings. Objective. To evaluate the efficacy of cryotherapy delivered by nurses for cervical intraepithelial neoplasia (CIN). Materials and methods. Direct visual inspection with acetic acid and lugol iodine (VIAVILI), and colposcopy/biopsy were performed on women 25 to 59 years old, residents of low-income areas in Bogotá, Colombia. Trained nurses offered immediate cryotherapy to every woman with positive visual inspection. Colposcopy/biopsy was performed before treatment and at a 12-month follow-up. The effectiveness was measured as cure (outcome: no-lesion) and regression (outcome: CIN1) rates of CIN2/3 using colposcopic and histological verification. Results. A group of 4.957 women with VIA/VILI was valuated. In total, 499 were screen positive and 472 accepted immediate treatment. A total of 365 women (11 CIN2/3) received cryotherapy by nurses. Cure rate was 72% (95%CI: 39%-94%) and 40% (95%CI: 22%-85%) by colposcopic and histological verification, respectively. Regression rates were 100% and 60%. There were two related non-serious adverse events. Conclusions. Cure and regression rates by colposcopic verification are like those reported for cryotherapy delivered by doctors. The sample size (CIN2/3) hinders comparisons by type of verification. Our findings support the implementation of screen-and-treat algorithms by nurses among populations with limited access to health services.

Introducción. El cáncer de cuello uterino es un problema de salud pública relevante en países de ingresos medios y bajos. El seguimiento de mujeres con tamización positiva y el acceso a tratamiento para neoplasia intraepitelial cervical (NIC) son retos mayores en estos países. Objetivo. Evaluar la efectividad de la crioterapia suministrada por enfermeras en casos de neoplasia intraepitelial de cérvix. Materiales y métodos. Se hizo la inspección visual directa con ácido acético y solución yodada (VIA-VILI), y se practicó colposcopia con biopsia, a mujeres entre los 25 y los 59 años, residentes en zonas de bajos ingresos de Bogotá. Profesionales de enfermería entrenados ofrecieron tratamiento inmediato con crioterapia a mujeres positivas en la inspección visual. Se les practicó colposcopia con biopsia antes del tratamiento y en un control a los 12 meses. Se evaluó la efectividad mediante tasas de curación (resultado: sin lesión) y regresión de NIC2/3 (resultado: ≤NIC1), por verificación colposcópica e histológica. Resultados. Se tamizaron 4.957 mujeres. En total, 499 fueron positivas y 472 aceptaron el tratamiento inmediato. Recibieron crioterapia por enfermería 365 mujeres (11 NIC2/3). La tasa de curación fue del 72 % (IC95%: 39-94 %) por verificación colposcópica, y del 40 % (IC95%: 22-85 %) por histología. Las tasas de regresión fueron del 100 y el 60 %, respectivamente. Se reportaron dos eventos adversos no graves relacionados.Conclusiones. Las tasas de curación y regresión por verificación colposcópica son similares a las reportadas con crioterapia administrada por médicos. El tamaño de la muestra con NIC2/3 dificulta la comparación por tipo de verificación. Los hallazgos apoyan la implementación de estrategias de "ver y tratar" por parte de enfermería en poblaciones con acceso limitado a servicios de salud.

Recentes avanços em biomarcadores para diagnóstico, prognóstico e avaliação terapêutica no câncer cervical / Recent advances in biomarkers for diagnosis, prognosis, and therapeutic evaluation in cervical cancer

Objetivos: revisar os estudos clínicos acerca de biomarcadores para o câncer cervical publicados nos últimos 10 anos, com foco no diagnóstico, prognóstico e avaliação do tratamento. Metodologia: as bases de dados PubMed, Web of Science e Science Direct foram pesquisadas utilizando os descritores "Uterine Cervical Neoplasms" e "Biomarkers". Foram selecionados os artigos originais publicados em inglês ou português, no período de 2011 a 2021. Após uma triagem pelos títulos e resumos dos artigos, aqueles relacionados ao objetivo do estudo foram lidos integralmente para a decisão final de inclusão na revisão. Os trabalhos que atenderam todos os critérios de seleção tiveram seus dados extraídos, principalmente, no que se refere ao tipo e objetivo do biomarcador proposto, população do estudo, tamanho da amostra, metodologia utilizada e principais desfechos obtidos. Resultados: esta estratégia de busca e seleção resultou em 22 artigos publicados nos últimos 10 anos na temática de interesse. Ocorreu um grande empenho na investigação de biomarcadores séricos para o câncer cervical, com a vantagem de serem minimamente invasivos. Houve destaque para marcadores genéticos e moleculares, como aqueles voltados para a metilação do DNA, detecção de polimorfismos, padrões de expressão de micro-RNA e expressão de genes relacionados à proliferação, imortalização e invasão celular. Conclusão: os dados reunidos encorajam a ampliação das pesquisas para aprimorar e validar a eficiência destes biomarcadores em grandes populações. É evidente o potencial dos biomarcadores como estratégia para melhorar o manejo do diagnóstico e o tratamento do câncer cervical, sendo que a utilização de marcadores genéticos parece ser o futuro dos biomarcadores para o câncer cervical

Aims: to review clinical studies on biomarkers for cervical cancer published in the last 10 years, focusing on the diagnosis, prognosis, and treatment evaluation. Methods: PubMed, Web of Science, and Science Direct databases were searched using the descriptors "Uterine Cervical Neoplasms" and "Biomarkers". Original articles published in English or Portuguese from 2011 to 2021 were selected. After screening by the titles and abstracts of the articles, those related to the objective of the study were read in full for the final decision of inclusion in the review. The studies that met all the selection criteria had their data extracted, especially regarding the type and objective of the biomarker proposed, study population, sample size, methodology used, and main outcomes obtained. Results: this search and selection strategy resulted in 22 articles published in the last 10 years on the topic of interest. There was a great effort to investigate serum biomarkers for cervical cancer, with the advantage of being minimally invasive. There was an emphasis on genetic and molecular markers, such as those focused on DNA methylation, detection of polymorphisms, expression patterns of microRNA, and expression of genes related to cell proliferation, immortalization, and invasion.Conclusions: the data gathered encourage expanded research to improve and validate the efficiency of these biomarkers in large populations. The potential of biomarkers as a strategy to improve the management of cervical cancer diagnosis and treatment is evident, and the use of genetic markers appears to be the future of biomarkers for cervical cancer

Distance to Multidisciplinary Team Clinic in Gaborone, Botswana, and Stage at Cervical Cancer Presentation for Women Living With and Without HIV.

PURPOSE: Cervical cancer is the leading cause of cancer death for women in Botswana. Barriers in access to cancer care can lead to later stages at diagnosis and increased mortality. This study evaluated access, defined as travel time from a patient's residential village to a multidisciplinary team clinic in Gaborone, with stage of cervical cancer at presentation. In addition, because of the high HIV prevalence in Botswana, we explored the association between travel time and HIV status. METHODS: Eligible patients with cervical cancer presenting to the multidisciplinary team between 2015 and 2020 were included. Data were abstracted from questionnaires and hospital records. Google Maps was used to calculate travel time. Multinomial regression was used to examine travel time and cancer stage, and multivariable logistic regression was used to investigate travel time and HIV status. RESULTS: We identified 959 patients with cervical cancer of which 70.1% were women living with HIV. The median travel time was approximately 2 hours. Using a reference group of stage I disease and a travel time of < 1 hour, the odds of presenting with stage II increased for patients traveling 3-5 hours (adjusted odds ratio [OR], 2.00; 95% CI, 1.14 to 3.52) and > 5 hours (OR, 2.19; 95% CI, 1.15 to 4.19). There were no significant associations for stage III. For stage IV disease, the odds were increased for patients traveling 3-5 hours (OR, 2.93; 95% CI, 1.26 to 6.79) and > 5 hours (adjusted OR, 4.05; 95% CI, 1.62 to 10.10). In addition, the odds of patients presenting living with HIV increased with increasing travel time (trend test = 0.004). CONCLUSION: This study identified two potential factors, travel time and HIV status, that influence access to comprehensive cervical cancer care in Botswana.

Proportions and incidence of locally advanced cervical cancer: a global systematic literature review.

BACKGROUND: Optimal treatment of cervical cancer is based on disease stage; therefore, an understanding of the global epidemiology of specific stages of locally advanced disease is needed. OBJECTIVE: This systematic literature review was conducted to understand the global and region-specific proportions of patients with cervical cancer with locally advanced disease and to determine the incidence of the locally advanced disease. METHODS: Systematic searches identified observational studies published in English between 2010 and June 10, 2020, reporting the proportion of patients with, and/or incidence of, locally advanced stages of cervical cancer (considered International Federation of Gynecology and Obstetrics (FIGO) IB2-IVA). Any staging criteria were considered as long as the proportion with locally advanced disease was distinguishable. For each study, the proportion of locally advanced disease among the cervical cancer population was estimated. RESULTS: The 40 included studies represented 28 countries in North or South America, Asia, Europe, and Africa. Thirty-eight studies reported the proportion of locally advanced disease among populations with cervical cancer. The estimated median proportion of locally advanced disease among all cervical cancer was 37.0% (range 5.6-97.5%; IQR 25.8-52.1%); estimates were generally lowest in North America and highest in Asia. Estimated proportions of ≥50% were reported in nine studies from Asia, Europe, Brazil, and Morocco; estimates ≤25% were reported in six studies from Asia, United States, Brazil, and South Africa. Locally advanced disease was reported for 44% and 49% of women aged >70 and ≥60 years, and 5-100% of younger women with cervical cancer. A greater proportion of locally advanced disease was reported for Asian American (19%) versus White women (8%) in one United States study. Two of five studies describing the incidence of locally advanced disease reported rates of 2-4/100 000 women among different time frames. CONCLUSION: This review highlights global differences in proportions of locally advanced cervical cancer, including regional variance and disparities according to patient race and age.

Factors contributing to delays in initiation of front-line cervical cancer therapy: disparities in a diverse south Florida population.

OBJECTIVE: Delay in initiating cervical cancer treatment may impact outcomes. In a cohort of patients initially treated by surgery, chemoradiation, chemotherapy, or in a clinical trial, we aim to define factors contributing to prolonged time to treatment initiation. METHODS: Data from patients initiating treatment for cervical cancer at a single institution was abstracted. Time to treatment initiation was defined as the interval from the date of cancer diagnosis to the date of treatment initiation. Poisson regression model was used for analysis. RESULTS: Of 274 patients studied, the median time to treatment initiation was 60 days (range 0-551). The median times to initiate surgery (54 days, range 3-96) and chemoradiation (58 days, range 4-187) were not significantly different (relative risk (RR) 1.01, 95% CI 0.98 to 1.04, p=0.54). The shortest median initiation time was for chemotherapy (47 days; RR 1.13, 95% CI 1.08 to 1.19, p<0.0001) and the longest was for clinical trial (62 days; RR 1.18, 95% CI 1.12 to 1.24, p<0.0001). Charity care (RR 1.09, 95% CI 1.05 to 1.14, p<0.0001), Medicare or Medicaid (RR 1.10, 95% CI 1.06 to 1.14, p<0.0001), and self-pay (RR 1.38, 95% CI 1.32 to 1.45, p<0.0001) delayed treatment initiation more than private insurance. Hispanic White women (RR 0.69, 95% CI 0.66 to 0.73, p<0.0001) had a shorter treatment initiation time compared with non-Hispanic White patients, while Afro-Caribbean/Afro-Latina women (RR 0.86, 95% CI 0.81 to 0.90, p<0.0001) and African-American patients (RR 1.13, 95% CI 1.07 to 1.19, p<0.0001) had longer initiation times. Spanish speaking patients did not have a prolonged treatment initiation (RR 0.68, 95% CI 0.66 to 0.71, p<0.0001), though Haitian-Creole speaking patients did (RR 1.07, 95% CI 1.01 to 1.13, p<0.002). Diagnosis at an outside institution delayed treatment initiation time (RR 1.24, 95% CI 1.18 to 1.30, p<0.0001) compared with diagnosis at the cancer center. CONCLUSION: Factors associated with prolonged time to treatment initiation include treatment modality, insurance status, language spoken, and institution of diagnosis. By closely examining each of these factors, barriers to treatment can be identified and modified to shorten treatment initiation time.

[Timely outpatient treatment of cervical cancer: the influence of region of residence for women in the state of Minas Gerais, Brazil]. / Tratamento ambulatorial do câncer do colo do útero em tempo oportuno: a influência da região de residência de mulheres no Estado de Minas Gerais, Brasil.

This study aimed to investigate whether there is an association between the Extended Health Regions (EHR) of residence in the state of Minas Gerais, Brazil, and the interval between diagnosis and start of treatment for women who underwent outpatient treatment (chemotherapy or radiotherapy) for cervical cancer by the Brazilian Unified National Health System (SUS), between 2001 and 2015. This is a cross-sectional study, part of a cohort with 8,857 women. Negative binomial regression models were used to evaluate the association of EHR of residence and the interval between diagnosis and start of treatment (in days), considering a significance level of 5%. The models were constructed using blocks of sociodemographic, clinical, and treatment-related covariates. It was found that the EHR of residence of women is associated with the interval between diagnosis and start of treatment. The northern EHR was the region of the state where the average time to start treatment was lower, and not residing in this EHR increases the average time to start treatment between 24% and 93% compared to other EHRs in the state. The disparity in the interval between diagnosis and start of treatment between the regions of Minas Gerais is evident. The availability of services enabled for the treatment of cancer in the EHRs does not necessarily results in a greater agility for the start of treatment. Understanding the flows of Oncology Care Networks and their regional differences is essential to improve public policies that ensure compliance with current laws, such as Law n. 12,732/2012, which recommends the start of treatment for cancer patients within 60 days after diagnosis.

O objetivo deste estudo é investigar se há associação entre as Regiões Ampliadas de Saúde (RAS) de residência de Minas Gerais, Brasil, e o intervalo entre diagnóstico e início de tratamento de mulheres que realizaram tratamento ambulatorial (quimioterapia ou radioterapia) para câncer do colo do útero pelo Sistema Único de Saúde (SUS), entre 2001 e 2015. Trata-se de um estudo transversal, recorte de uma coorte, com 8.857 mulheres. Para avaliar a associação da RAS de residência e o intervalo entre diagnóstico e início de tratamento (em dias), foram utilizados modelos de regressão binomial negativa, considerando nível de significância de 5%. Os modelos foram construídos usando blocos de covariáveis sociodemográficas, clínicas e relacionadas ao tratamento. Foi determinado que a RAS de residência das mulheres está associada ao intervalo entre o diagnóstico e o início de tratamento. A RAS Norte foi a região do estado onde a média de tempo para iniciar o tratamento foi menor, e não residir nessa RAS aumenta a média de tempo para iniciar o tratamento entre 24% e 93% em comparação com outras RAS do estado. Fica evidente a disparidade no intervalo entre diagnóstico e início de tratamento entre as regiões do Estado de Minas Gerais. A disponibilidade de serviços habilitados para o tratamento do câncer nas RAS não reflete necessariamente em maior agilidade para início de tratamento. Compreender os fluxos das Redes de Atenção Oncológica e suas diferenças regionais é fundamental para aprimorar políticas públicas que garantam o cumprimento de leis vigentes, como a Lei nº 12.732/2012, que preconiza o início do tratamento de pacientes com câncer em até 60 dias após o diagnóstico.

El objetivo de este estudio es investigar si existe una asociación entre las Regiones Ampliadas de Salud (RAS) de residencia en Minas Gerais, Brasil, y el intervalo entre el diagnóstico y el inicio del tratamiento para mujeres que realizaron tratamiento ambulatorio (quimioterapia o radioterapia) para cáncer de cuello uterino por el Sistema Único de Salud (SUS) entre 2001 y 2015. Se trata de un estudio transversal, recortado de una cohorte, con 8.857 mujeres. Para evaluar la asociación entre la RAS de residencia y el intervalo entre el diagnóstico y el inicio del tratamiento (en días), se utilizaron modelos de regresión binomial negativa, considerando el nivel de significancia del 5%. Los modelos se construyeron utilizando bloques de covariables sociodemográficas, clínicas y relacionadas con el tratamiento. Se encontró una asociación entre la RAS de residencia de las mujeres y el intervalo entre el diagnóstico y el inicio del tratamiento. La región de la RAS Norte tuvo tiempo promedio más corto para el inicio del tratamiento, pero si las mujeres no residen en esta RAS el tiempo promedio para el inicio del tratamiento puede aumentar entre el 24% y el 93% en comparación con otras RAS del estado. Queda evidente la disparidad del intervalo entre el diagnóstico y el inicio del tratamiento entre las regiones de Minas Gerais. La disponibilidad de servicios habilitados para el tratamiento del cáncer en la RAS no necesariamente refleja la mayor rapidez para el inicio del tratamiento. Es fundamental comprender los flujos de las Redes de Atención Oncológica y sus diferencias regionales para buscar mejorar las políticas públicas que garantizan el cumplimiento de la legislación vigente, como la Ley nº 12.732/2012, que recomienda que el tratamiento de los pacientes con cáncer debe empezar dentro de los 60 días posteriores al diagnóstico.