Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society.

The American Cancer Society (ACS) recommends that individuals with a cervix initiate cervical cancer screening at age 25 years and undergo primary human papillomavirus (HPV) testing every 5 years through age 65 years (preferred); if primary HPV testing is not available, then individuals aged 25 to 65 years should be screened with cotesting (HPV testing in combination with cytology) every 5 years or cytology alone every 3 years (acceptable) (strong recommendation). The ACS recommends that individuals aged >65 years who have no history of cervical intraepithelial neoplasia grade 2 or more severe disease within the past 25 years, and who have documented adequate negative prior screening in the prior 10 years, discontinue all cervical cancer screening (qualified recommendation). These new screening recommendations differ in 4 important respects compared with the 2012 recommendations: 1) The preferred screening strategy is primary HPV testing every 5 years, with cotesting and cytology alone acceptable where access to US Food and Drug Administration-approved primary HPV testing is not yet available; 2) the recommended age to start screening is 25 years rather than 21 years; 3) primary HPV testing, as well as cotesting or cytology alone when primary testing is not available, is recommended starting at age 25 years rather than age 30 years; and 4) the guideline is transitional, ie, options for screening with cotesting or cytology alone are provided but should be phased out once full access to primary HPV testing for cervical cancer screening is available without barriers. Evidence related to other relevant issues was reviewed, and no changes were made to recommendations for screening intervals, age or criteria for screening cessation, screening based on vaccination status, or screening after hysterectomy. Follow-up for individuals who screen positive for HPV and/or cytology should be in accordance with the 2019 American Society for Colposcopy and Cervical Pathology risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors.

Definitive radiotherapy consisting of external beam radiotherapy without central shielding and 3D image-guided brachytherapy for patients with cervical cancer: feasibility for Japanese patients and dose-response analyses for local control in the low-dose range.

OBJECTIVE: To assess the feasibility of external beam radiotherapy without central shielding in definitive radiotherapy for Japanese patients with cervical cancer. METHODS: We retrospectively analysed the data of cervical cancer patients treated with definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy. RESULTS: The study included 167 patients (T1 + 2 = 108, T3 + 4 = 59) from eight Japanese institutions. For three-dimensional-image-guided brachytherapy, intra-cavitary and interstitial brachytherapy was utilized in 33 patients (20%). The median follow-up was 26.6 months (interquartile range, 20-43.2). The maximum rectal D2 (75 Gy)/bladder D2 (90 Gy) constraints were deviated by 6%/10% and 10%/5% for T1 + 2 and T3 + 4, respectively. The 2-year incidence of ≥grade 3 proctitis/cystitis was 4%/1% for T1 + 2 and 10%/2% for T3 + 4. The 2-year local progression-free survival was 89% for T1 + 2 and 82% for T3 + 4. For T1 + 2, the 2-year local progression-free survival for the high-risk clinical target volume D90 ≥ 68 Gy (indicated by receiver operating characteristic analysis; area under the curve = 0.711) was 92% versus 67% for <68 Gy (log-rank; P = 0.019). Cox multivariate analysis indicated that the high-risk clinical target volume D90 was one of independent predictors of local failure (P = 0.0006). For T3 + 4, the 2-year local progression-free survival was 87% for the high-risk clinical target volume <82 cm3 (area under the curve = 0.67) and 43% for ≥82 cm3 (P = 0.0004). Only the high-risk clinical target volume was an independent predictor of local failure (P = 0.0024). CONCLUSIONS: Definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy was feasible for Japanese patients with cervical cancer. Dose de-escalation from the current global standards is suggested for patients with T1 + 2 disease.

Definitive radiotherapy consisting of whole pelvic radiotherapy with no central shielding and CT-based intracavitary brachytherapy for cervical cancer: feasibility, toxicity, and oncologic outcomes in Japanese patients.

BACKGROUND: This prospective study investigated the feasibility, toxicity, and oncologic outcomes of definitive radiotherapy (RT) consisting of whole pelvic radiotherapy with no central shielding (noCS-WPRT) and CT-based intracavitary brachytherapy (ICBT) in Japanese patients with cervical cancer. METHODS: Patients with cervical cancer of FIGO stages IB1-IVA were eligible. The treatment protocol consisted of noCS-WPRT of 45 Gy in 25 fractions and CT-based high dose-rate ICBT of 15 or 20 Gy in 3 or 4 fractions prescribed at point A. The prescribed ICBT dose was decreased if the manual dwell time/position optimization failed to meet organs-at-risk constraints. Graphical optimization and additional interstitial needles were not applied. RESULTS: We enrolled 40 patients. FIGO stages were IB1: 11, IB2: 13, IIA2: 1, IIB: 11, IIIB: 3, and IVA: 1. Median (range) pretreatment tumor diameter was 47 (14-81) mm. Point A doses were decreased in 19 of 153 ICBT sessions (12%). The median follow-up duration was 33 months. The 2-year rates of pelvic control, local control (LC), and progression-free survival were 83%, 85%, and 75%, respectively. Pre-ICBT tumor diameter, high-risk clinical target volume (HR-CTV), total HR-CTV D90, and overall treatment time (OTT) significantly affected LC. Late adverse events (grade ≥ 3) were observed in 3 patients (2 in the bladder, 1 in the rectum). CONCLUSIONS: Definitive RT consisting of noCS-WPRT and CT-based ICBT was feasible for Japanese patients with cervical cancer. To further improve LC, additional interstitial needles for patients with a large HR-CTV and shorter OTT should be considered.

Quantitative and mixed analyses to identify factors that affect cervical cancer screening uptake among lesbian and bisexual women and transgender men.

AIMS AND OBJECTIVES: The purposes of this study were to measure the prevalence of, and identify factors associated with, cervical cancer screening among a sample of lesbian, bisexual and queer women, and transgender men. BACKGROUND: Past research has found that lesbian, bisexual and queer women underuse cervical screening service. Because deficient screening remains the most significant risk factor for cervical cancer, it is essential to understand the differences between routine and nonroutine screeners. DESIGN: A convergent-parallel mixed methods design. METHODS: A convenience sample of 21- to 65-year-old lesbian and bisexual women and transgender men were recruited in the USA from August-December 2014. Quantitative data were collected via a 48-item Internet questionnaire (N = 226), and qualitative data were collected through in-depth telephone interviews (N = 20) and open-ended questions on the Internet questionnaire. RESULTS: Seventy-three per cent of the sample was routine cervical screeners. The results showed that a constellation of factors influence the use of cervical cancer screening among lesbian, bisexual and queer women. Some of those factors overlap with the general female population, whereas others are specific to the lesbian, bisexual or queer identity. Routine screeners reported feeling more welcome in the health care setting, while nonroutine screeners reported more discrimination related to their sexual orientation and gender expression. Routine screeners were also more likely to 'out' to their provider. The quantitative and qualitative factors were also compared and contrasted. CONCLUSIONS: Many of the factors identified in this study to influence cervical cancer screening relate to the health care environment and to interactions between the patient and provider. RELEVANCE TO CLINICAL PRACTICE: Nurses should be involved with creating welcoming environments for lesbian, bisexual and queer women and their partners. Moreover, nurses play a large role in patient education and should promote self-care behaviours among lesbian women and transgender men.

Uterine collision tumor. Case report and review of the literature / Tumor de colisión de útero. Reporte de caso y revisión de la literatura

Objectives: To report the case of a patient with a uterine collision tumor and to conduct a review of the literature. Material and methods: A 76-year-old patient who presented to the national cancer referral center in Bogota (Colombia), where she was diagnosed with a uterine collision tumor consisting of a seroustype endometrial adenocarcinoma and a cervical adenosarcoma. The patient underwent surgical treatment followed by chemotherapy and supplemental radiotherapy, and died 16 months later. A search was conducted in the Medline via PubMed and Embase databases, including reports and case series of women with a diagnosis of uterine collision tumor, with retrieval of information regarding diagnosis, treatment and prognosis. A narrative summary of the findings was made. Results: The search identified 36 titles, of which 14 studies with 17 patients were included. The most frequent histopathological diagnosis was endometrial adenocarcinoma and high and low grade endometrial sarcoma (47 %). Primary treatment was surgery and adjuvant treatment with chemotherapy and radiotherapy (15 %) was performed in close to 50 % of cases. One-year survival was 75 %. Conclusions: No cases of uterine collision tumors with the histopathology or in the location of the reported case were found in the literature. If this reported case is taken into account, 2-year mortality is 28 %. Further studies to describe the immunohistochemistry, treatment and prognosis of this condition are needed.

Objetivos: reportar el caso de una paciente con tumor de colisión del útero y realizar una revisión de la literatura respecto al diagnóstico histopatológico, tratamiento y pronóstico de esta condición. Materiales y métodos: mujer de 76 años que consultó al centro nacional de referencia del cáncer en Bogotá (Colombia), donde se hizo el diagnóstico de tumor de colisión del útero, compuesto por un adenocarcinoma de endometrio tipo seroso y adenosarcoma de cérvix. Recibió tratamiento quirúrgico más quimioterapia y radioterapia complementaria, falleció a los 16 meses. Se realizó una búsqueda de la literatura en las bases de datos Medline vía PubMed y Embase, que incluía reportes y series de caso de mujeres con diagnóstico de tumor de colisión del útero, y se extrajo información sobre el diagnóstico, tratamiento y pronóstico. Se realizó un resumen narrativo de los hallazgos. Resultados: la búsqueda identificó 36 títulos, de los cuales se incluyeron 14 estudios que incluían 17 pacientes. El diagnóstico histopatológico más frecuente fue el adenocarcinoma endometrioide de endometrio y sarcoma endometrial de alto y bajo grado (47 %). El tratamiento básico fue quirúrgico. Cerca del 50 % recibió tratamiento adyuvante con quimioterapia y radioterapia (15 %). La sobrevida a 1 año fue del 75 %. Conclusiones: en la literatura no se identificaron casos de tumores de colisión de útero con la histopatología y en la ubicación del caso presentado. La mortalidad a dos años es cercana al 28 % si se toma en cuenta el caso reportado. Se necesitan más estudios que describan la inmunohistoquímica, el tratamiento y el pronóstico de esta condición.

Study of the Relationship between ABO Blood Group Types and Breast Cancer and Cervix Cancer in Khuzestan Province, Iran.

Background: Breast cancer and cervix cancer are the prevalent and deadly types of solid tumors around the world. According to the importance of cancer, it is necessary to understand predisposing factors that affect cancer risk. In this regard, previous studies suggest that blood types particularly ABO and Rh-Hr Blood-Group System could play roles in the risk and different features of cancers. In the present study, we aimed to evaluate the potential of ABO and Rh blood groups as risk factors for breast cancer and cervix cancer. Materials and Methods: A retrospective study included 109 and 14 patients diagnosed with breast cancer and cervix cancer, respectively with known ABO and Rh blood types, between 2018 and 2020 in Khuzestan province, Iran. For compression of ABO blood groups distribution between the cancer patients group and the healthy population, we used data from a large-scale study that report the distribution of ABO blood groups in 29,922 blood donors in Khuzestan province. Results: Based on obtained results the most frequent blood group is O followed by B, A, and AB in breast cancer and followed by A, B, and AB in cervix cancer. Results showed no significant association between ABO and Rh and the risk of breast and cervix cancer. Moreover, there is no relationship between blood types and clinic pathological features of breast cancer.   Conclusion:  Based on our data, ABO and in this regard, previous studies suggest that blood types particularly ABO and Rh-Hr Blood-Group System could play roles in the risk and different features of cancers. In the present study, we aimed to evaluate the potential of ABO and Rh blood groups as risk factors for breast cancer and cervix cancer do have not any association with the risk of breast and cervix cancer and their characteristics.

Primary HPV-DNA screening in women under 30 years of age: health technology assessment / Tamización primaria con prueba ADN-VPH en mujeres menores de 30 años: evaluación de tecnología sanitaria

Background: Primary screening with Human Papilloma Virus (HPV) testing was introduced in Colombia in 2014 for individuals between 30 and 65 years of age. When the result is positive, cytology triage is performed for colposcopy referral. The convenience of initiating HPV-DNA testing for screening at 25 years of age is currently a subject of discussion. Therefore, the objective of this health technology assessment (HTA) is to analyze the available evidence regarding safety, efficacy, cost-effectiveness, values and preferences, ethical dilemmas and considerations pertaining to the implementation of the HPV-DNA test as a cervical screening strategy in women under 30 years of age in the Colombian context. Domains to be assessed: Clinical efficacy and safety 1. Cumulative rate of cervical intraepithelial neoplasia (CIN) grade 2 or high-er after 2 screening rounds. 2. Cumulative rates of invasive cancer of the uterine cervix after 2 screening rounds. 3. Safety: referral to colposcopy. Cost-effectiveness Cost-effectiveness for Colombia. Other domains considered Ethical considerations associated with cervical screening in women under 30 years of age. Organizational and individual considerations. Barriers and facilitators pertaining to the implementation of cervical screening in women under 30 years of age in the Colombian context. Methods: Clinical efficacy and safety assessment A systematic literature search of systematic reviews and clinical trials was conducted in MEDLINE, Embase and CENTRAL. The body of evidence was rated using the GRADE approach. An interdisciplinary team was then convened to create a working group to review the retrieved evidence. This led to the discussion and construction of the conclusions following the guidelines of a formal consensus in accordance with the RAND/UCLA methodology. Economic study Systematic literature research of studies that had assessed cost-effectiveness for Colombia. Results: Clinical outcomes An integrative analysis of 5 randomized clinical trials that met the inclusion critera was performed. Compared with cytology, primary HPV-DNA testing in women under 30 years of age could be associated with a lower frequency of CIN+2 lesions during the first screening round (RR: 1.57; CI: 1.20 to 2.04; low evidence certainty), and a lower incidence of CIN+2 (RR: 0.67; CI: 0.48 to 0.92; low evidence certainty). Moreover, it is associated with a lower frequency of invasive carcinoma at the end of follow-up (RR: 0.19; CI: 0.07 to 0.53; high evidence certainty). Economic results From the financial point of view, the use of HPVDNA testing plus cytology-based triage starting at 25 years of age is perhaps the most cost-effective option for Colombia (incremental cost-effectiveness ratio, COP 8,820,980 in 2013). Other implications Two studies suggest that barriers to implementation attributable to intermediation, public unrest and geographic considerations could be overcome with the use of new screening technologies or strategies. It is important to consider administration and service provision alternatives in order to overcome some acceptability and access barriers. Any cervical screening program must take into consideration ethical principles of nonmaleficence, beneficence, autonomy and equity. Future studies should focus on analyzing new screening techniques with emphasis on the population under 30 years of age. Conclusions: The use of HPV-DNA testing as a screening strategy in women under 30 years of age is a potentially efficacious and cost-effective intervention for Colombia. Future studies should focus on analyzing new screening technologies, with emphasis on the population under 30 years of age.

Antecedentes: A partir del 2014 en Colombia se incorporó la Tamización primaria con prueba de Virus del Papiloma Humano (VPH) desde los 30 hasta los 65 años, cuando la prueba es positiva se hace triage con citología para remisión a colposcopia. Actualmente se discute la conveniencia de iniciar la tamización con prueba de ADN de VPH a partir de los 25 años. De esta manera, el objetivo de esta evaluación de tecnologías sanitarias es analizar la evidencia disponible en torno a la seguridad, efectividad, costoefectividad, valores y preferencias, dilemas éticos y aspectos relacionados con la implementación para el contexto colombiano de la prueba ADN-VPH como estrategia de tamización cervical en mujeres menores de 30 años. Dominios a evaluar: Eficacia clínica y seguridad 1. Tasa acumulada de neoplasia intraepitelial cervical (NIC) grado 2 o más avanzado luego de 2 rondas de tamización. 2. Tasas acumuladas de cáncer invasor de cérvix luego de 2 rondas de tamización. 3. Seguridad: remisión a colposcopia. Costo-efectividad Costo efectividad para Colombia. Otros dominios considerados Aspectos éticos asociados a la tamización cervical en mujeres menores de 30 años. Aspectos organizacionales y del individuo. Barreras y facilitadores relacionados con la implementación en el contexto colombiano de la tamización cervical en mujeres menores de 30 años. Métodos: Evaluación de efectividad y seguridad clínicas Se realizó una búsqueda sistemática de la literatura en MEDLINE, Embase y CENTRAL de revisiones sistemáticas y ensayos clínicos. Se calificó el cuerpo de la evidencia con la aproximación GRADE. Posteriormente, se convocó a un grupo interdisciplinario a una mesa de trabajo en donde se presentó la evidencia recuperada, dando paso a la discusión y a la construcción de las conclusiones, siguiendo los lineamientos de un consenso formal acorde a la metodología RAND/UCLA. Estudio económico Se hizo una búsqueda sistemática de la literatura de estudios que hubieran evaluado el costo-efectividad para Colombia. Resultados: De 7.659 referencias recuperadas se incluyeron 8 estudios. Resultados clínicos Se realizó un análisis integrativo de 5 ensayos clínicos aleatorizados que cumplieron con los criterios de inclusión. Cuando se compara frente a la citología, la tamización primaria con ADN-VPH en mujeres menores de 30 años, podría asociarse con una mayor frecuencia de detección de lesiones NIC2+ durante la primera ronda de cribado (RR: 1.57; IC: 1,20 a 2,04; certeza en la evidencia baja), con una menor incidencia de NIC2+ (RR:0,67; IC: 0,48 a 0,92; certeza en la evidencia baja) y se asocia con una menor frecuencia de carcinoma invasor al término del seguimiento (RR: 0,19; IC: 0,07 a 0,53; certeza en la evidencia alta). Resultados económicos Desde el punto de vista económico, la alternativa de ADN-VPH y triage con citología desde los 25 años quizás representa la alternativa más costo-efectiva para Colombia (razón costo-efectividad incremental $8.820.980 COP año 2013). Otras implicaciones Dos estudios sugieren que las barreras de implementación, atribuibles a circunstancias de intermediación, de orden público y de carácter geográfico, podrían ser solventadas por nuevas tecnologías o estrategias de cribado. Es importante considerar alternativas de forma de administración y de prestación de servicios para solventar algunas barreras de aceptabilidad y acceso. Todo programa de tamización cervical debe contemplar los principios éticos de no maleficencia, beneficencia, autonomía y equidad. Futuros estudios deben enfocarse en analizar nuevas tecnologías de cribado con énfasis en población menor de 30 años. Conclusiones: El uso de la prueba ADN-VPH como estrategia de tamización en mujeres menores de 30 años es una intervención probablemente efectiva y costoefectiva para Colombia. Futuros estudios deben enfocarse en analizar nuevas tecnologías de cribado con énfasis en población menor de 30 años.

Comparison of Synthetic Computed Tomography Generation Methods, Incorporating Male and Female Anatomical Differences, for Magnetic Resonance Imaging-Only Definitive Pelvic Radiotherapy.

PURPOSE: There are several means of synthetic computed tomography (sCT) generation for magnetic resonance imaging (MRI)-only planning; however, much of the research omits large pelvic treatment regions and female anatomical specific methods. This research aimed to apply four of the most popular methods of sCT creation to facilitate MRI-only radiotherapy treatment planning for male and female anorectal and gynecological neoplasms. sCT methods were validated against conventional computed tomography (CT), with regard to Hounsfield unit (HU) estimation and plan dosimetry. METHODS AND MATERIALS: Paired MRI and CT scans of 40 patients were used for sCT generation and validation. Bulk density assignment, tissue class density assignment, hybrid atlas, and deep learning sCT generation methods were applied to all 40 patients. Dosimetric accuracy was assessed by dose difference at reference point, dose volume histogram (DVH) parameters, and 3D gamma dose comparison. HU estimation was assessed by mean error and mean absolute error in HU value between each sCT and CT. RESULTS: The median percentage dose difference between the CT and sCT was <1.0% for all sCT methods. The deep learning method resulted in the lowest median percentage dose difference to CT at -0.03% (IQR 0.13, -0.31) and bulk density assignment resulted in the greatest difference at -0.73% (IQR -0.10, -1.01). The mean 3D gamma dose agreement at 3%/2 mm among all sCT methods was 99.8%. The highest agreement at 1%/1 mm was 97.3% for the deep learning method and the lowest was 93.6% for the bulk density method. Deep learning and hybrid atlas techniques gave the lowest difference to CT in mean error and mean absolute error in HU estimation. CONCLUSIONS: All methods of sCT generation used in this study resulted in similarly high dosimetric agreement for MRI-only planning of male and female cancer pelvic regions. The choice of the sCT generation technique can be guided by department resources available and image guidance considerations, with minimal impact on dosimetric accuracy.

Validation of an MRI-only planning workflow for definitive pelvic radiotherapy.

PURPOSE: Previous work on Magnetic Resonance Imaging (MRI) only planning has been applied to limited treatment regions with a focus on male anatomy. This research aimed to validate the use of a hybrid multi-atlas synthetic computed tomography (sCT) generation technique from a MRI, using a female and male atlas, for MRI only radiation therapy treatment planning of rectum, anal canal, cervix and endometrial malignancies. PATIENTS AND METHODS: Forty patients receiving radiation treatment for a range of pelvic malignancies, were separated into male (n = 20) and female (n = 20) cohorts for the creation of gender specific atlases. A multi-atlas local weighted voting method was used to generate a sCT from a T1-weighted VIBE DIXON MRI sequence. The original treatment plans were copied from the CT scan to the corresponding sCT for dosimetric validation. RESULTS: The median percentage dose difference between the treatment plan on the CT and sCT at the ICRU reference point for the male cohort was - 0.4% (IQR of 0 to - 0.6), and - 0.3% (IQR of 0 to - 0.6) for the female cohort. The mean gamma agreement for both cohorts was > 99% for criteria of 3%/2 mm and 2%/2 mm. With dose criteria of 1%/1 mm, the pass rate was higher for the male cohort at 96.3% than the female cohort at 93.4%. MRI to sCT anatomical agreement for bone and body delineated contours was assessed, with a resulting Dice score of 0.91 ± 0.2 (mean ± 1 SD) and 0.97 ± 0.0 for the male cohort respectively; and 0.96 ± 0.0 and 0.98 ± 0.0 for the female cohort respectively. The mean absolute error in Hounsfield units (HUs) within the entire body for the male and female cohorts was 59.1 HU ± 7.2 HU and 53.3 HU ± 8.9 HU respectively. CONCLUSIONS: A multi-atlas based method for sCT generation can be applied to a standard T1-weighted MRI sequence for male and female pelvic patients. The implications of this study support MRI only planning being applied more broadly for both male and female pelvic sites. Trial registration This trial was registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) ( www.anzctr.org.au ) on 04/10/2017. Trial identifier ACTRN12617001406392.

Prevalence and Associated Factors of Precancerous Cervical Lesions among Women in Ethiopia: A Systematic Review and Meta-Analysis.

BACKGROUND: Cervical cancer remains the most common cancer of women worldwide. Its burden is more serious in developing countries. It is also the second common cancer deaths of women in Ethiopia followed by breast cancer. The aim of this study was to determine the pooled prevalence and associated factors of precancerous cervical lesions among women in Ethiopia. METHODS: We systematically searched published and unpublished articles reported from 2010 to 2019 using a comprehensive search of electronic databases including PubMed and Google scholar for grey literature from August 1 to September 1, 2019. The methodological qualities of included studies were evaluated using Joanna Briggs Institute meta-analysis of Statistics Assessment. The pooled prevalence estimate was calculated using MedCalc software-version 19.0.7, and the pooled odd ratios for predictors was calculated using RevMan software version 5.3. RESULTS: The pooled prevalence of precancerous cervical lesions among women in Ethiopia was 13.4% (95% CI:10.63% 16.37%). Statistically significant heterogeneity between studies was detected (I2=83.1%, P < 0.001). Among all measured associated factors: numbers of women life time sexual partners > 1, OR=2.5 (95% CI:3.70,4.76), being HIV positive women, OR=2.4 (95% CI:1.33,4.61) and women having history of STI, OR=2.0 (95% CI:1.02,3.87) had statistically significant association with precancerous cervical lesions among women in Ethiopia. CONCLUSION: The pooled prevalence of precancerous cervical lesions among women in Ethiopia was high as compared to the 5-year worldwide cervical cancer prevalence. Women having more than one life time sexual partners, being HIV positive women and women having history of STI had a statistically significant association with precancerous cervical lesions.

Obesity and gynecological cancers: A toxic relationship.

Despite the evidence supporting the relevance of obesity and obesity-associated disorders in the development, management, and prognosis of various cancers, obesity rates continue to increase worldwide. Growing evidence supports the involvement of obesity in the development of gynecologic malignancies. This article explores the molecular basis governing the alteration of hallmarks of cancer in the development of obesity-related gynecologic malignancies encompassing cervical, endometrial, and ovarian cancers. We highlight specific examples of how development, management, and prognosis are affected for each cancer, incorporate current knowledge on complementary approaches including lifestyle interventions to improve patient outcomes, and highlight how new technologies are helping us better understand the biology underlying this neglected pandemic.

Clinical response and safety of apatinib monotherapy in recurrent, metastatic cervical cancer after failure of chemotherapy: a retrospective study.

OBJECTIVE: To observe the safety and short-term efficacy of apatinib in the treatment of recurrent, metastatic cervical cancer in patients who have already received more than two kinds of comprehensive treatment. METHODS: Forty-eight patients with recurrent or metastatic cervical cancer after radiotherapy or surgery who received apatinib between June 2016 and June 2017 were involved in this study. These patients experienced progression after first-line or second-line chemotherapy. There were 38 patients with cervical squamous cell carcinoma, 8 with adenocarcinoma, and 2 with adenosquamous carcinoma. Progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were reviewed and evaluated. RESULTS: All patients had complete follow-up records, and the median follow-up time was 14.5 months (5.5-20.5 months). Among the 48 patients, 14.58% achieved a partial response and 52.08% achieved stable disease. The overall response rate and disease control rate were 14.58% and 66.67%, respectively. The median time that the 48 patients received oral apatinib was 8.2 months. The median PFS was 4.6 months (95% confidence interval [CI]=3.31-5.26) and OS was 13.9 months (95% CI=8.37-17.96). The main apatinib-related adverse reactions were leukopenia (37.5%), neutropenia (41.67%), hemorrhage (37.5%), hypertension (33.33%), proteinuria (12.5%), fatigue (37.5%), and hand-foot syndrome (27.08%). Most of them were grade 1-2, and no drug-related death occurred. CONCLUSIONS: Apatinib can improve the disease control rate of recurrent and metastatic cervical cancer when chemotherapy has failed, and the treatment is well tolerated. This represents that apatinib may be a new treatment option for metastatic cervical cancer patients.

Diversity of human papillomavirus typing among women population living in rural and remote areas of Brazilian territory.

OBJECTIVES: Genotyping HPV from samples tested positive to careHPV™ assay in rural and remote areas of Brazilian territory. METHODS: A total of 5079 women were enrolled in an opportunistic screening from the Barretos Cancer Hospital, through mobile units or ambulatory unit. All careHPV™ hr-HPV positive samples were tested by a Luminex-based protocol in order to evaluate the HPV infecting types. RESULTS: Positive hr-HPV results were obtained in 10.6% (536/5068) of women. Among these cases, HPV-56 and HPV-51 were the most common types detected in 32.3% and 31.4%, respectively. HPV-53 (20.5%), HPV-18 (18.5%), HPV-58 (17.6%), HPV-52 (16.0%) and HPV-16.6%) were the other most frequent types detected. These frequencies represent prevalences of 2.35%, 2.12%, 2.02%, 1.84% and 1.80% respectively, within the population studied. Regarding low-risk HPVs, HPV-6 was detected in 12.9% of the samples. The less frequent types (<3%) were: HPV-70, HPV-11 and HPV-26. CONCLUSIONS: The most frequent types detected were: HPV-56, HPV-51, HPV-53, HPV-18, HPV-58, HPV-52 and HPV-16 according to decreasing rates.

Tumor de colisión de útero. Reporte de caso y revisión de la literatura / Uterine collision tumor. Case report and review of he literature

Objetivos: Reportar el caso de una paciente con tumor de colisión del útero y realizar una revisión de la literatura respecto al diagnóstico histopatológico, tratamiento y pronóstico de esta condición. Materiales y métodos: Mujer de 76 años que consultó al centro nacional de referencia del cáncer en Bogotá (Colombia), donde se hizo el diagnóstico de tumor de colisión del útero, compuesto por un adenocarcinoma de endometrio tipo seroso y adenosarcoma de cérvix. Recibió tratamiento quirúrgico más quimioterapia y radioterapia complementaria, falleció a los 16 meses. Se realizó una búsqueda de la literatura en las bases de datos Medline vía PubMed y Embase, que incluía reportes y series de caso de mujeres con diagnóstico de tumor de colisión del útero, y se extrajo información sobre el diagnóstico, tratamiento y pronóstico. Se realizó un resumen narrativo de los hallazgos. Resultados: La búsqueda identificó 36 títulos, de los cuales se incluyeron 14 estudios que incluían 17 pacientes. El diagnóstico histopatológico más frecuente fue el adenocarcinoma endometrioide de endometrio y sarcoma endometrial de alto y bajo grado (47 %). El tratamiento básico fue quirúrgico. Cerca del 50 % recibió tratamiento adyuvante con quimioterapia y radioterapia (15 %). La sobrevida a un año fue del 75 %. Conclusiones: En la literatura no se identificaron casos de tumores de colisión de útero con la histopatología y en la ubicación del caso presentado. La mortalidad a dos años es cercana al 28 % si se toma en cuenta el caso reportado. Se necesitan más estudios que describan la inmunohistoquímica, el tratamiento y el pronóstico de esta condición.

Objectives: To report the case of a patient with a uterine collision tumor and to conduct a review of the literature. Material and methods: A 76-year-old patient who presented to the national cancer referral center in Bogota (Colombia), where she was diagnosed with a uterine collision tumor consisting of a serous-type endometrial adenocarcinoma and a cervical adenosarcoma. The patient underwent surgical treatment followed by chemotherapy and supplemental radiotherapy, and died 16 months later. A search was conducted in the Medline via PubMed and Embase databases, including reports and case series of women with a diagnosis of uterine collision tumor, with retrieval of information regarding diagnosis, treatment and prognosis. A narrative summary of the findings was made. Results: The search identified 36 titles, of which 14 studies with 17 patients were included. The most frequent histopathological diagnosis was endometrial adenocarcinoma and high and low grade endometrial sarcoma (47 %). Primary treatment was surgery and adjuvant treatment with chemotherapy and radiotherapy (15 %) was performed in close to 50 % of cases. One-year survival was 75 %. Conclusions: No cases of uterine collision tumors with the histopathology or in the location of the reported case were found in the literature. If this reported case is taken into account, 2-year mortality is 28 %. Further studies to describe the immunohistochemistry, treatment and prognosis of this condition are needed.

Prevalência de alterações de exame citopatológico e sua relação com lesões compatíveis com a infecção pelo Papiloma Vírus Humano e as neoplasias do colo uterino / Prevalence of changes on cytopathological exams and their relationship with injuries compatible with human papilloma virus infection and uterine cervical neoplasms

Introdução: O objetivo deste estudo é identificar a frequência de exames citológicos de colo uterino alterados e sua relação com a infecção pelo Papiloma Vírus Humano (HPV) e neoplasias. Métodos: Foram estudadas mulheres residentes em zona urbana, que fizeram exame citopatológico entre 2015 e 2017, com registros no Sistema de Informações do Câncer. Resultados: Foram realizados 25.323 exames citopatológicos, reunindo 815 alterações (3,2%). A faixa etária mais acometida foi entre 30-40 anos. A principal alteração encontrada foi "ASC-US" (431 casos ­ 52,8%). A Lesão Intraepitelial de Baixo Grau, que compreende o efeito citopático pelo HPV e neoplasia intraepitelial cervical Grau I, foi encontrada em 164 casos (20,1%). Após exame de colposcopia, 181 pacientes realizaram biópsia, sendo mais prevalente "NIC I com Alterações Compatíveis com Ação pelo HPV" (21,5%). Conclusão: Elevada prevalência de alterações que podem evoluir para neoplasias de colo uterino, com ênfase naquelas sugestivas da presença de HPV em pacientes abaixo de 25 anos.

Introduction: This study aimed to identify the frequency of changes on cervix cytopathological exams and its relationship with Human Papilloma Virus (HPV) infection and neoplasms. Methods: Women living in the urban area who underwent cytopathological examination from 2015 to 2017 were assessed, based on records from the Cancer Information System. Results: A total of 25,323 cytopathological exams were performed, reporting 815 changes (3.2%). The most affected age group was from 30 to 40 years. The most frequent change was "ASC-US" (431 cases ­ 52.8%). Low-grade intraepithelial lesion, which encompasses the cytopathic effect of HPV and cervical intraepithelial neoplasm grade I, was found in 164 cases (20.1%). After being examined by colposcopy, 181 patients underwent biopsy, whose most prevalent finding was "grade I CIN with Changes Compatible With HPV Action" (21.5%). Conclusion: There was a high prevalence of changes that can evolve to uterine cervical neoplasms, with emphasis on those suggestive of presence of HPV in patients younger than 25 years.

Tamización primaria con prueba ADN-VPH en mujeres menores de 30 años: evaluación de tecnología sanitaria / Primary HPV-DNA screening in women under 30 years of age: health technology assessment

Antecedentes A partir del 2014 en Colombia se incorporó la Tamización primaria con prueba de Virus del Papiloma Humano (VPH) desde los 30 hasta los 65 años, cuando la prueba es positiva se hace triage con citología para remisión a colposcopia. Actualmente se discute la conveniencia de iniciar la tamización con prueba de ADN de VPH a partir de los 25 años. De esta manera, el objetivo de esta evaluación de tecnologías sanitarias es analizar la evidencia disponible en torno a la seguridad, efectividad, costoefectividad, valores y preferencias, dilemas éticos y aspectos relacionados con la implementación para el contexto colombiano de la prueba ADN-VPH como estrategia de tamización cervical en mujeres menores de 30 años. Dominios a evaluar Eficacia clínica y seguridad 1. Tasa acumulada de neoplasia intraepitelial cervical (NIC) grado 2 o más avanzado luego de 2 rondas de tamización. 2. Tasas acumuladas de cáncer invasor de cérvix luego de 2 rondas de tamización. 3. Seguridad: remisión a colposcopia. Costo-efectividad Costo efectividad para Colombia. Otros dominios considerados Aspectos éticos asociados a la tamización cervical en mujeres menores de 30 años. Aspectos organizacionales y del individuo. Barreras y facilitadores relacionados con la implementación en el contexto colombiano de la tamización cervical en mujeres menores de 30 años. Métodos Evaluación de efectividad y seguridad clínicas Se realizó una búsqueda sistemática de la literatura en MEDLINE, Embase y CENTRAL de revisiones sistemáticas y ensayos clínicos. Se calificó el cuerpo de la evidencia con la aproximación GRADE. Posteriormente, se convocó a un grupo interdisciplinario a una mesa de trabajo en donde se presentó la evidencia recuperada, dando paso a la discusión y a la construcción de las conclusiones, siguiendo los lineamientos de un consenso formal acorde a la metodología RAND/UCLA. Estudio económico Se hizo una búsqueda sistemática de la literatura de estudios que hubieran evaluado el costo-efectividad para Colombia. Resultados De 7.659 referencias recuperadas se incluyeron 8 estudios. Resultados clínicos Se realizó un análisis integrativo de 5 ensayos clínicos aleatorizados que cumplieron con los citerios de inclusión. Cuando se compara frente a la citología, la tamización primaria con ADN-VPH en mujeres menores de 30 años, podría asociarse con una mayor frecuencia de detección de lesiones NIC2+ durante la primera ronda de cribado (RR: 1.57; IC: 1,20 a 2,04; certeza en la evidencia baja), con una menor incidencia de NIC2+ (RR:0,67; IC: 0,48 a 0,92; certeza en la evidencia baja) y se asocia con una menor frecuencia de carcinoma invasor al término del seguimiento (RR: 0,19; IC: 0,07 a 0,53; certeza en la evidencia alta). Resultados económicos Desde el punto de vista económico, la alternativa de ADN-VPH y triage con citología desde los 25 años quizás representa la alternativa más costo-efectiva para Colombia (razón costo-efectividad incremental $8.820.980 COP año 2013). Otras implicaciones Dos estudios sugieren que las barreras de implementación, atribuibles a circunstancias de intermediación, de orden público y de carácter geográfico, podrían ser solventadas por nuevas tecnologías o estrategias de cribado. Es importante considerar alternativas de forma de administración y de prestación de servicios para solventar algunas barreras de aceptabilidad y acceso. Todo programa de tamización cervical debe contemplar los principios éticos de no maleficencia, beneficencia, autonomía y equidad. Futuros estudios deben enfocarse en analizar nuevas tecnologías de cribado con énfasis en población menor de 30 años. Conclusiones El uso de la prueba ADN-VPH como estrategia de tamización en mujeres menores de 30 años es una intervención probablemente efectiva y costoefectiva para Colombia. Futuros estudios deben enfocarse en analizar nuevas tecnologías de cribado con énfasis en población menor de 30 años.

Background Primary screening with Human Papilloma Virus (HPV) testing was introduced in Colombia in 2014 for individuals between 30 and 65 years of age. When the result is positive, cytology triage is performed for colposcopy referral. The convenience of initiating HPV-DNA testing for screening at 25 years of age is currently a subject of discussion. Therefore, the objective of this health technology assessment (HTA) is to analyze the available evidence regarding safety, efficacy, cost-effectiveness, values and preferences, ethical dilemmas and considerations pertaining to the implementation of the HPV-DNA test as a cervical screening strategy in women under 30 years of age in the Colombian context. Domains to be assessed Clinical efficacy and safety 1. Cumulative rate of cervical intraepithelial neoplasia (CIN) grade 2 or high-er after 2 screening rounds. 2. Cumulative rates of invasive cancer of the uterine cervix after 2 screening rounds. 3. Safety: referral to colposcopy Cost-effectiveness Cost-effectiveness for Colombia. Other domains considered Ethical considerations associated with cervical screening in women under 30 years of age. Organizational and individual considerations. Barriers and facilitators pertaining to the implementation of cervical screening in women under 30 years of age in the Colombian context. Methods Clinical efficacy and safety assessment A systematic literature search of systematic reviews and clinical trials was conducted in MEDLINE, Embase and CENTRAL. The body of evidence was rated using the GRADE approach. An interdisciplinary team was then convened to create a working group to review the retrieved evidence. This led to the discussion and construction of the conclusions following the guidelines of a formal consensus in accordance with the RAND/UCLA methodology. Economic study Systematic literature research of studies that had assessed cost-effectiveness for Colombia. Results Out of the 7,659 references retrieved, 8 studies were included. Clinical outcomes An integrative analysis of 5 randomized clinical trials that met the inclusion critera was performed. Compared with cytology, primary HPV-DNA testing in women under 30 years of age could be associated with a lower frequency of CIN+2 lesions during the first screening round (RR: 1.57; CI: 1.20 to 2.04; low evidence certainty), and a lower incidence of CIN+2 (RR: 0.67; CI: 0.48 to 0.92; low evidence certainty). Moreover, it is associated with a lower frequency of invasive carcinoma at the end of follow-up (RR: 0.19; CI: 0.07 to 0.53; high evidence certainty). Economic results From the financial point of view, the use of HPVDNA testing plus cytology-based triage starting at 25 years of age is perhaps the most cost-effective option for Colombia (incremental cost-effectiveness ratio, COP 8,820,980 in 2013). Other implications Two studies suggest that barriers to implementation attributable to intermediation, public unrest and geographic considerations could be overcome with the use of new screening technologies or strategies. It is important to consider administration and service provision alternatives in order to overcome some acceptability and access barriers. Any cervical screening program must take into consideration ethical principles of nonmaleficence, beneficence, autonomy and equity. Future studies should focus on analyzing new screening techniques with emphasis on the population under 30 years of age. Conclusions The use of HPV-DNA testing as a screening strategy in women under 30 years of age is a potentially efficacious and cost-effective intervention for Colombia. Future studies should focus on analyzing new screening technologies, with emphasis on the population under 30 years of age.

Repercussões da braquiterapia na qualidade de vida e funcionalidade no tratamento do câncer de colo uterino / Effects of brachytherapy on quality of life and functionality in the treatment of cervix cancer / Efectos de la braquiterapia sobre la calidad de vida y la funcionalidad en el tratamiento del cáncer de cuello uterino

RESUMO Objetivo: avaliar a repercussão da braquiterapia sobre funcionalidade e qualidade de vida de mulheres com câncer de colo uterino. Método: estudo transversal descritivo, desenvolvido entre dezembro de 2019 e fevereiro de 2020, com 33 mulheres com neoplasia uterina em tratamento braquiterápico, acompanhadas no Centro Oncológico do Nordeste - Brasil. Foi aplicado o instrumento Funtional Assessment of Cancer Theraphy - Cervix Cancer. Foram comparadas as médias das subescalas e analisada a correlação entre elas por meio da aplicação dos testes ANOVA e t de Student. Resultados: foram evidenciadas demandas voltadas para a autoimagem, sexualidade e queixas urinárias. A média de preocupações adicionais foi menor na faixa de 50-59 quando comparada com a média da faixa de 31-49 (p=0,004) e com a de 60-75 (p=0,002). Conclusão: abordar assuntos voltados para sexualidade e queixas urinárias contribuem para a identificação precoce dos sintomas ocasionados pela braquiterapia, assim como implementação de medidas, proporcionando qualidade de vida à paciente.

ABSTRACT Objective: to assess the effect of brachytherapy on functionality and quality of life of women with cervix cancer. Method: a descriptive and cross-sectional study carried out between December 2019 and February 2020 with 33 women with uterine neoplasia undergoing brachytherapy, followed up at Centro Oncológico do Nordeste - Brazil. The Funtional Assessment of Cancer Therapy - Cervix Cancer instrument was applied. The means of the subscales were compared and their mutual correlation was analyzed by applying the ANOVA and Student's t tests. Results: requirements focused on self-image, sexuality and urinary complaints were evidenced. The mean of additional concerns was lower in the age group from 50 to 59 years old, when compared to the mean values in the age groups from 31 to 49 years old (p=0.004) and from 60 to 75 years old (p=0.002). Conclusion: addressing issues related to sexuality and urinary complaints contribute to early identification of the symptoms caused by brachytherapy, as well as the implementation of measures, providing quality of life for the patient.

RESUMEN Objetivo: evaluar el efecto de la braquiterapia sobre la funcionalidad y la calidad de vida de mujeres con cáncer de cuello uterino. Método: estudio transversal y descriptivo realizado entre diciembre de 2019 y febrero de 2020 con 33 mujeres con neoplasia uterina en tratamiento de braquiterapia, monitoreadas en el Centro Oncológico do Nordeste - Brasil. Se aplicó el instrumento Funtional Assessment of Cancer Therapy - Cervix Cancer. Se compararon las medias de las subescalas y se analizó la correlación entre ellas por medio de las pruebas ANOVA y t de Student. Resultados: se evidenciaron requerimientos centrados en la autoimagen, la sexualidad y las quejas urinarias. La media de preocupaciones adicionales fue menor en los grupos etarios de 31 a 49 años (p=0.004) y de 60 a 75 (p=0.002). Conclusión: abordar cuestiones relacionadas con la sexualidad y las molestias urinarias contribuyen a la identificación precoz de los síntomas causados por la braquiterapia, así como a la implementación de medidas, proporcionando calidad de vida a la paciente.

Primary signet ring cell adenocarcinoma of the uterine cervix - A rare neoplasm that raises the question of metastasis to the cervix.

Primary signet ring cell adenocarcinoma is extremely rare. Signet ring cell carcinoma is more commonly primary in the stomach or breast, and the more likely metastatic disease to the cervix needs to be ruled out. We present a case of primary signet ring cell carcinoma of the cervix and review the literature.

Positive endocervical margins at conization: repeat conization or colposcopic follow-up? A retrospective study.

BACKGROUND: The presence of residual cervical lesions was evaluated in patients submitted to repeat conization due to a finding of positive endocervical margins in a previous loop electrosurgical excision procedure (LEEP) specimen. In addition, the correlation between the presence of a residual lesion and risk factors for cervical cancer, and the use of repeat conization as first-choice treatment were analyzed. METHODS: This retrospective study included 44 patients submitted to repeat cervical conization or total hysterectomy following a finding of affected endocervical margins in LEEP specimens. The risk factors analyzed in relation to the presence of residual lesions were age, smoking, cone depth, glandular involvement and the histopathology findings of cervical intraepithelial neoplasia (CIN) 1, CIN 2 or CIN 3/carcinoma in situ. The Chi-square test and the Mann-Whitney t-test were used, with significance defined at P < 0.05. RESULTS: Residual lesions were found in 23/44 patients (52.3%), with 3/23 cases (13.0%) being compatible with invasive squamous cell carcinoma. Of the 23 patients, six (26.1%) were submitted to total hysterectomy, with one case being compatible with a moderately differentiated invasive squamous cell carcinoma. Two patients with a histopathology finding of CIN 3/carcinoma in situ in the previous LEEP specimen were diagnosed with invasive squamous cell carcinoma in the repeat conization specimen. Residual lesions were not significantly associated with the risk factors evaluated. CONCLUSIONS: In view of the high frequency of residual disease found when positive endocervical margins were found in LEEP specimens, the indication for repeat cervical conization rather than colposcopic follow-up is viable and justified. Indeed, since the presence of a residual lesion and its progression in the cervical canal are more difficult to screen and control, patients unable to comply with regular colposcopic follow-up could benefit from repeat conization when trying to avoid a potentially negative outcome.

EGFR protein expression and gene amplification in squamous intraepithelial lesions and squamous cell carcinomas of the cervix.

The purpose of this study was to evaluate the protein expression and gene amplification of epithelial growth factor receptor (EGFR) in intraepithelial neoplasias and squamous cell carcinoma of the cervix and to determine the value of EGFR in carcinogenesis, progression, and prognosis of cervical cancer. EGFR protein expression and gene amplification involved gene copy number in 75 cases of cervical various lesions were evaluated using immunohistochemistry and by fluorescence in situ hybridization (FISH) techniques. Expression of EGFR was observed in 76.00% of the high-grade CIN and 79.17% of the invasive carcinomas. In contrast, there were low levels of EGFR expression in chronic cervicitis (1/10) and low-grade CIN (7/16). There were statistically significant differences among them (P<0.05). Gene amplification was detected in 20.51% high-grade CIN and invasive carcinoma, but there only 4.35% EGFR gene amplification was observed in chronic cervicitis and low grade CIN. Among the 42 patients with negative or low levels of EGFR expression, 26 patients (61.90%) were found to have diploidy and 11 patients (26.20%) to have balanced triploidy. However, among the 20 patients with an intermediate and high levels of EGFR protein expression, 13 (65.00%) were found to have balanced polyploidy or gene amplification. All cases of EGFR gene amplification involved intermediate and high levels of protein expression. EGFR may be involved in the carcinogenesis of the cervix and may be an early event during the carcinogenesis. Overexpression of EGFR protein may result from gene amplification and increases in gene copy number.