Predictors of Endocrine Resistance in a Cohort of Mexican Breast Cancer Patients.

Purpose: This study aimed to determine the prevalence of endocrine resistance in a cohort of Hispanic Mexican breast cancer (BC) patients receiving care at Instituto Nacional de Cancerología (INCan). Additionally, the clinical-pathological factors associated with endocrine resistance were identified, and their impact on patient survival was explored. Methods: A retrospective analysis of 200 BC patients who attended INCan between 2012 and 2016 with estrogen receptor (ER) and progesterone receptor (PR) positive tumors was made. Endocrine resistance was defined according to the International Consensus Guidelines for Advance Breast Cancer 2 definition. Their clinicopathological characteristics were analyzed to determine the association with endocrine resistance presence. We used sensitivity analyses and multivariate-adjusted logistic regressions, Kaplan-Meier curves, and multivariate-adjusted Cox regressions. P-value < 0.05 was considered as statistically significant. Results: Endocrine resistance was observed in 32.5% of patients included in this study. The distinction between hormone resistance and sensitivity was influenced by tumor size and node status. It had a mean diameter of 7.15 cm in endocrine resistance cases compared to 5.71 cm in non-endocrine, with N3 status present in 20% of endocrine resistance cases versus only 2.2% in non-endocrine (p-value < 0.001). The clinical stage exhibited a strong association with endocrine resistance (Risk Ratio [RR] 4.39, 95% confidence interval [95%CI] 1.50, 11.43). Furthermore, endocrine resistance significantly impacted mortality during the follow-up, with a Hazard Ratio [HR] of 23.7 (95%CI 5.20, 108.42) in multivariable-adjusted models. However, a complete pathological response reduced the endocrine resistance risk, as demonstrated by a Risk Ratio (RR) of 0.15 (95% CI 0.03, 0.75). Conclusions: Advanced clinical stage at diagnosis predicted endocrine resistance in Hispanic Mexican BC patients. Complete pathologic response in locally advanced disease patients was also a key predictor of endocrine resistance. These results indicated that endocrine resistance was a critical factor in BC during follow-up.

Current status and challenges in timely detection of cervical cancer in Mexico: expert consensus.

Cervical cancer is a significant public health problem in low- and middle-income countries, accounting for 85% of new cases worldwide. Due to poorly organized screening programs, cervical cancer is more likely to develop in vulnerable groups who do not initiate or rarely undergo screening. Cervical cytology and detecting high-risk human papillomavirus types are the recommended screening tools. Further, these strategies allow for accurately identifying women at a higher risk of cervical cancer and establishing screening times. New detection tools, such as novel biomarkers or automatic HPV detection in the vagina or urine, can improve screening coverage. This review aims to identify the challenges faced by detection programs and screening tools in Mexico to provide evidence-based recommendations to improve early detection programs for cervical cancer.

Factors Associated with Parametrial Involvement in Endometrial Carcinoma in Patients Treated with Radical Hysterectomy.

INTRODUCTION: Describe factors associated with parametrial involvement, and how these factors modify the prognosis of patients with endometrial carcinoma treated with radical hysterectomy. METHODS: Observational study in which categorized patients according to those with and without parametrial involvement. A descriptive analysis and comparative analysis were performed for associations between parametrial spread and clinical, surgical, and pathology variables. RESULTS: We analyzed 85 patients, which 18 (21%) had parametrial involvement. Pathology factors associated with parametrial involvement were the endometrioid subtype, grade 3, and variants of poor prognosis (odds ratio (OR) 3.41, 95% CI 1.09-10.64; P = 0.035), myometrial invasion of over 50% (OR 7.76, 95% CI 1.65-36.44; P = 0.009), serosal involvement (OR 17.07, 95% CI 3.87-75.35; P < 0.001), ovarian metastasis (OR 5.15, 95% CI 1.36-19.46; P = 0.016), positive peritoneal cytology (OR 3.9, 95% CI 1.04-14.77; P = 0.044), and lymph node metastasis (OR 3.4; 95% CI 1.16-9.97; P = 0.026). Five-year disease-free survival was 74% (95% CI 57.4-85.4) for the group without parametrial spread and 50.8% (95% CI 22.7-73.4) for the group with parametrial spread (P = 0.001). Similarly, 5-year overall survival was 85.2% (95% CI 67.9-93.6) for the group without parametrial spread and 47.5% (95% CI 8.1-80.2) for the group with parametrial spread (P = 0.002). CONCLUSION: Factors associated with parametrial involvement were histologies of poor prognosis, tumors affecting uterine serosa, cervix, or spread beyond the uterus. Additionally, parametrial involvement directly affects prognosis by reducing overall survival, disease-free survival and increasing odds for recurrence.

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.

Factors associated with emergency room readmission after elective surgery for ovarian carcinoma.

BACKGROUND: Hospital readmission is a quality metric of hospital care and has been studied in ovarian carcinoma, but its evaluation has several limitations. Also, emergency room (ER) readmission is considered an adverse effect because it represents patient costs. Therefore, our objective was to determine the rate of ER readmission, its causes, and associated factors. METHODS: A retrospective study of 592 patients with ovarian carcinoma who underwent upfront surgery, neoadjuvant therapy, or surgery for recurrent disease. An analysis of factors associated with ER readmission, hospital readmission, and surgical complications was performed, including multivariate analysis to assess for case-mix factors. RESULTS: Of 592 patients, the median age was 51 years, and the predominant type of treatment was the neoadjuvant approach (52.9%); 46% underwent upfront surgeries and six surgeries for recurrence. The ratio to ER readmission was 11.8% (70 patients), of whom 12 patients were admitted more than once. The factors associated with ER readmission were prolonged surgery, intraoperative bleeding, extended hospital stay, the time of the day when the surgery was performed, and post-surgical complications. The hospital readmissions were 4.2%, and the overall morbidity was 17.6%. In the multivariate analysis, the only factor associated with ER readmission was the presence of surgical complications (OR = 39.01). The factors independently associated with hospital readmission were the entrance to the intensive care unit (OR = 1.37), the presence of surgical complications (OR = 2.85), and ER readmission (OR = 1.45). CONCLUSION: ER readmission is an adverse event representing the presence of symptoms/complications in patients. Evaluating the ER readmission independently of the readmission to the hospital is critical because it will allow modifying medical care behaviors to prevent patients from unnecessarily returning to the hospital after a hospital discharge to manage preventable medical problems. TRIAL REGISTRATION: researchregistry7882.

Analysis of Mexican young women with primary ovarian insufficiency induced by gynaecological and haematological cancer management.

This was a retrospective study that included 114 women younger than 40 years with induced primary ovarian insufficiency. Patients who presented vasomotor symptoms had a higher proportion (26 [63.41%] versus 58 [79.45%], OR 2.23, 95% CI 0.95-5.23, p = .065) to initiate hormone replacement therapy. Vasomotor symptoms were present in patients with ovarian cancer (OR 0.27, 95% CI 0.09-0.8, p = .18), haematologic cancer (OR 0.11, 95% CI 0.2-0.65, p = .014), radiotherapy (OR 2.62, 95% CI 1.04-6.54, p = .039) and chemotherapy with radiotherapy (OR 2.72, 95% CI 1.01-7.35, p = .049). Having ovarian or haematological cancer, being managed with radiotherapy and/or chemotherapy, and having follicle-stimulating hormone parameters higher than 35 mUI/mL are factors that significantly increase the risk of presenting vasomotor symptoms.Impact StatementWhat is already known on this subject? In young women with cancer, induced primary ovarian insufficiency can result as an ovarian surgery or as an adverse effect of chemotherapy or radiotherapy. Regardless of aetiology, patients are going to manifest early climacteric symptoms with an increased risk for cardiovascular disease, metabolic syndrome and osteoporosis.What do the results of this study add? Patients who presented vasomotor symptoms had initially a higher proportion of hormone replacement therapy. Patients that were treated exclusively with radiotherapy or with chemotherapy and concomitant radiotherapy have a significantly increased risk to manifest vasomotor symptoms.What are the implications of these findings for clinical practice and/or future research? Having ovarian or haematological cancer, being managed with radiotherapy and/or chemotherapy and having follicle-stimulating hormone parameters higher than 35 mUI/mL are factors that significantly increase the risk of presenting vasomotor symptoms.

Supervivencia y factores asociados en pacientes con cáncer cervicouterino atendidas por el Seguro Popular en México.

 Objetivo. Estimar la supervivencia a cinco años por cáncer cervicouterino y sus factores asociados en pacientes mexica-nas, cuya atención fue financiada por el Fondo de Protección contra Gastos Catastróficos (FPGC) del Seguro Popular durante el periodo 2006-2014. Material y métodos. Se analizó la base de datos de las pacientes mencionadas y se vinculó con el Subsistema Epidemiológico y Estadístico de Defunciones. Se hizo un análisis de supervivencia a cinco años por etapa clínica y factores asociados, mediante el método de Kaplan-Meier y los modelos de riesgos proporcionales de Cox. Resultados. La supervivencia global por cáncer cervicouterino a los cinco años fue de 68.5%. Los factores asociados fueron la etapa clínica (locoregional [HR=2.8 IC95% HR: 2.6,3.0] y metastásica [HR=5.4 IC95% HR: 4.9,5.9]) com-parada con la etapa temprana y la edad (HR=1.003 IC95% HR:1.001,1.004). Conclusiones. Las mujeres que lograron el acceso a la atención del cáncer cervical financiadas por el FPGC tuvieron una supervivencia ligeramente superior a las reportadas en otros estudios.

Tumor histology is an independent prognostic factor in locally advanced cervical carcinoma: A retrospective study.

BACKGROUND: Even with different histologic origins, squamous cell carcinoma (SCC) and adenocarcinoma (AC) are considered a single entity, and the first-line treatment is the same. Locally advanced disease at the diagnosis of cervical cancer is the most important prognostic factor, the recurrence rate is high, making it necessary to evaluate prognostic factors other than clinical or radiological staging; histology could be one of them but continues to be controversial. The aim of this study was to evaluate tumor histology as a prognostic factor in terms of treatment outcomes, disease-free survival (DFS) and overall survival (OS) in a retrospective cohort of patients with Locally Advanced Cervical Carcinoma (LACC). METHODS: The records of 1291patients with LACC were reviewed, all of them were treated with 45-50 Gy of external beam radiotherapy with concurrent chemotherapy and brachytherapy. A descriptive and comparative analysis was conducted. Treatment response was analyzed by the chi-square test; DFS and OS were calculated for each histology with the Kaplan-Meier method and compared with the log-rank test; and the Cox model was applied for the multivariate analysis. RESULTS: We included 1291 patients with LACC treated from 2005 to 2014, of which 1154 (89·4%) had SCC and 137 (10·6%) had AC. Complete response to treatment was achieved in 933 (80·8%) patients with SCC and 113 (82·5%) patients with AC. Recurrence of the disease was reported in 29·9% of SCC patients and 31·9% of AC patients. Five-year DFS was 70% for SCC and 62·2% for AC. The five-year OS rates were 74·3% and 60% for SCC and AC, respectively. The mean DFS was 48·8 months for SCC vs 46·10 for AC (p = 0·043), the mean OS was 50·8 for SCC and 47·0 for AC (p = 0·002). CONCLUSION: Our findings support the hypothesis that SCC and AC are different clinical entities. TRIAL REGISTRATION: NCT04537273 .

Supervivencia y factores asociados en pacientes con cáncer cervicouterino atendidas por el Seguro Popular en México / Survival analysis and associated factors in patients with cervical cancer financed by the Seguro Popular in Mexico

Resumen: Objetivo: Estimar la supervivencia a cinco años por cáncer cervicouterino y sus factores asociados en pacientes mexicanas, cuya atención fue financiada por el Fondo de Protección contra Gastos Catastróficos (FPGC) del Seguro Popular durante el periodo 2006-2014. Material y métodos: Se analizó la base de datos de las pacientes mencionadas y se vinculó con el Subsistema Epidemiológico y Estadístico de Defunciones. Se hizo un análisis de supervivencia a cinco años por etapa clínica y factores asociados, mediante el método de Kaplan-Meier y los modelos de riesgos proporcionales de Cox. Resultados: La supervivencia global por cáncer cervicouterino a los cinco años fue de 68.5%. Los factores asociados fueron la etapa clínica (locoregional [HR=2.8 IC95% HR: 2.6,3.0] y metastásica [HR=5.4 IC95% HR: 4.9,5.9]) comparada con la etapa temprana y la edad (HR=1.003 IC95% HR:1.001,1.004). Conclusiones: Las mujeres que lograron el acceso a la atención del cáncer cervical financiadas por el FPGC tuvieron una supervivencia ligeramente superior a las reportadas en otros estudios.

Abstract: Objective: Estimate five-year survival from cervical cancer and associated factors in Mexican patients financed by Seguro Popular during the period 2006-2014. Materials and methods: We analyzed the database of patients financed by the Catastrophic Expenses Protection Fund and linked it to the Statistical and Epidemiological System of mortality. We performed a five-year survival analysis by clinical stage and associated factors, using the Kaplan-Meier method and Cox proportional hazards models. Results: Overall survival for cervical cancer at five years was 68.5%. The associated factors were the clinical stage: locoregional (HR=2.8 CI95% HR: 2.6,3.0) and metastatic (HR=5.4 CI95% HR: 4.9,5.9) compared to early stage and age (HR=1.003 CI95% HR:1.001,1.004). Conclusions: Women who gained access to Catastrophic Expenses Protection Fund cervical cancer care had similar survival than that reported in other studies.

microRNA Profile Associated with Positive Lymph Node Metastasis in Early-Stage Cervical Cancer.

Lymph node metastasis (LNM) is an important prognostic factor in cervical cancer (CC). In early stages, the risk of LNM is approximately 3.7 to 21.7%, and the 5-year overall survival decreases from 80% to 53% when metastatic disease is identified in the lymph nodes. Few reports have analyzed the relationship between miRNA expression and the presence of LNM. The aim of this study was to identify a subset of miRNAs related to LNM in early-stage CC patients. Formalin-fixed paraffin-embedded tissue blocks were collected from patients with early-stage CC treated by radical hysterectomy with lymphadenectomy. We analyzed samples from two groups of patients-one group with LNM and the other without LNM. Global miRNA expression was identified by microarray analysis, and cluster analysis was used to determine a subset of miRNAs associated with LNM. Microarray expression profiling identified a subset of 36 differentially expressed miRNAs in the two groups (fold change (FC) ≥ 1.5 and p < 0.01). We validated the expression of seven miRNAs; miR-487b, miR-29b-2-5p, and miR-195 were underexpressed, and miR-92b-5p, miR-483-5p, miR-4534, and miR-548ac were overexpressed according to the microarray experiments. This signature exhibited prognostic value for identifying early-stage CC patients with LNM. These findings may help detect LNM that cannot be observed in imaging studies.

Post-recurrence survival in patients with cervical cancer.

BACKGROUND: Up to 26% of patients with early-stage cervical cancer experience relapse after primary surgery. However, little is known about which factors influence prognosis following disease recurrence. Therefore, our aims were to determine post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors for PR-DSS. METHODS: Data from 528 patients with early-stage cervical cancer who relapsed after primary surgery performed between 2007 and 2016 were obtained from the SCANN study (Surveillance in Cervical CANcer). Factors related to the primary disease and recurrence were combined in a multivariable Cox proportional hazards model to predict PR-DSS. RESULTS: The 5-year PR-DSS was 39.1% (95% confidence interval [CI] 22.7%-44.5%), median disease-free interval between primary surgery and recurrence (DFI1) was 1.5 years, and median survival after recurrence was 2.5 years. Six significant variables were identified in the multivariable analysis and were used to construct the prognostic model. Two were related to primary treatment (largest tumour size and lymphovascular space invasion) and four to recurrence (DFI1, age at recurrence, presence of symptoms, and recurrence type). The C-statistic after 10-fold cross-validation of prognostic model reached 0.701 (95% CI 0.675-0.727). Three risk-groups with significantly differing prognoses were identified, with 5-year PR-DSS rates of 81.8%, 44.6%, and 12.7%. CONCLUSIONS: We developed the robust model of PR-DSS to stratify patients with relapsed cervical cancer according to risk profiles using six routinely recorded prognostic markers. The model can be utilised in clinical practice to aid decision-making on the strategy of recurrence management, and to better inform the patients.

Association of p16 and Ki-67 with Risk of Recurrence in Previously Treated Cervical High-Grade Squamous Intraepithelial Lesions.

OBJECTIVE: Our main objective was to assess the association between the markers p16 and Ki-67 and recurrence of disease in patients previously treated for cervical high-grade squamous intraepithelial lesion (HSIL). DESIGN: This is a case-control study at the National Cancer Institute conducted between 2005 and 2015. Of the patients with a pathologically confirmed diagnosis of HSIL, 107 cases were selected. They were divided into 2 groups: 28 cases with recurrence after treatment and a control group of 79 patients without recurrence. We identified clinical, pathological, and treatment variables. METHODS: Two experienced pathologists performed immunohistochemical analysis of biomarkers; they agreed on their interpretation, and we calculated the odds ratios (ORs) associated with recurrence. For group comparisons, we used the Wilcoxon signed-rank, χ2, or Fisher's exact test, depending on the type of variable. We conducted logistic regression models to estimate ORs and determine the factors associated with recurrence. The recurrence-free period was defined as the time frame between conization and either recurrence of disease or the last date the patient was seen. We used Kaplan-Meier plots to visualize survival curves and log-rank tests to compare the curves. We established a p value <0.05 as statistically significant. RESULTS: After pathologists performed immunohistochemical analysis, they achieved an agreement level of 83.7% for p16 and 60% for Ki-67. We did not find an association between recurrence and either p16 expression (p = 0.69) or the percentage of Ki-67 expression (p = 0.71). The recurrence-free period analysis did not reveal a difference in p16 expression (p = 0.57) nor in the percentage of Ki-67 expression in the 3-tiered scale (p = 0.56). LIMITATIONS: Our main limitation was a reduced sample size. CONCLUSION: We found no association between p16 and Ki-67 positivity and the risk of recurrence in previously treated HSIL.

The usefulness of intraoperative consultation for the diagnosis of borderline ovarian tumors.

BACKGROUND: Borderline ovarian tumors (BTs) must be recognized during the surgery by intraoperative consultation (IOC) to guide surgical treatment; however, this diagnosis can be imprecise. Therefore, this study aimed to evaluate the diagnostic accuracy of IOC for the diagnosis of BT. METHODS: A retrospective cohort study was carried out including all women diagnosed with a pelvic tumor consecutively surgically treated from 2005 to 2015 with IOC. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios (LR) for the IOC and BTs. RESULTS: A total of 758 patients were enrolled, the median age was 44 years, the median tumor size was 11.8 cm, and the median CA-125 levels were 45.65 U/µL. After IOC, 458 (64.1%) cases were diagnosed as benign, 111 (14.7%) as BT, and 161 (21.2%) as malignant. The definitive diagnosis was a benign tumor in 448 (59.1%) cases, BT in 110 (14.5%), and 200 (26.4%) cases were malignant. The diagnostic accuracy of the IOC for BT diagnosis was 89.8% (sensitivity =65.5%, specificity =93.9%). The diagnosis performance of IOC for the diagnosis between BT and benign tumors (n=546) had a sensitivity of 69.9%, a specificity of 98.4%, and a diagnostic accuracy of 84%; meanwhile for the diagnosis between BT and malignant tumors (n=242) IOC had a sensitivity of 92.3%, a specificity of 81.7%, and a diagnostic accuracy of 87%. CONCLUSIONS: For practitioners, knowing the accuracy and limitations of the IOC for BT enables the better selection of cases to perform a complete staging surgery.

Prognostic significance of the mad1l1 1673 g:a polymorphism in ovarian adenocarcinomas

Abstract Background: Ovarian cancer is the most lethal gynecologic cancer. Although most patients respond adequately to the first-line therapy, up to 85% experience a recurrence of disease, which carries a poor prognosis. Mitotic arrest deficiency 1 is a protein that helps in the assembly of the mitotic spindle assembly checkpoint by preventing anaphase until all chromatids are properly aligned. A single-nucleotide polymorphism in the MAD1L1 gene is prevalent in patients with advanced epithelial ovarian cancer and alters the way in which it responds to chemotherapy. Objective: The objective of the study was to study the relationship between the rs1801368 polymorphism of MAD1L1 and prognosis of ovarian adenocarcinoma. Methods: A total of 118 patients in whom the MAD1L1 gene was sequenced were analyzed using descriptive and comparative statistics. Results: Patients carrying the wild-type genotype had a higher distribution of early-stage disease. Having a MAD1L1 polymorphic allele increased the risk of being non-sensitive to chemotherapy. The median disease-free survival for patients with the wild-type MAD1L1 was 46.93 months, compared to 10.4 months for patients with at least one polymorphic allele. Conclusions: The rs1801368 polymorphism of MAD1L1 gene worsens prognosis in patients with ovarian adenocarcinoma. Traditional therapy for ovarian cancer might not be optimal in patients carrying this polymorphism.

THERAPEUTIC USE OF HUMAN PAPILLOMAVIRUS VACCINES IN CERVICAL LESIONS.

Human papillomavirus (HPV) has been associated with the development of precancerous lesions of the cervix and cervical cancer (CC). Prophylactic HPV vaccination induces the development of a specific memory immune response that facilitates HPV elimination once the natural infection occurs. At present, in addition to the prophylactic vaccine, therapeutic vaccines are being developed and researched with the aim of inducing an immune response that allows the elimination of HPV-infected cells. The purpose of this study is to describe the current evidence on the use of therapeutic vaccines and their effect on cervical precancerous lesions, to establish recommendations on their clinical use. So far, the studies that have generated results have described a marginal beneficial effect of the prophylactic vaccine in the management of infection and pre-invasive lesions. Based on the evidence, continuing research on the efficacy and safety of therapeutic vaccines for the treatment of cervical intraepithelial lesions is recommended. The use of the HPV prophylactic vaccine as treatment for pre-existing lesions is not advised, but it is recommended to prevent new lesions.

Diagnostic performance of intraoperative assessment in grade 2 endometrioid endometrial carcinoma.

BACKGROUND: Endometrial carcinoma is the most common gynecologic malignancy in developed countries. Grade 2 carcinoma is associated with pelvic lymph-node metastasis, depending on selected risk factors. Intraoperative assessment (IOA) can identify patients at risk for lymph node metastasis who should undergo staging surgery. Our objective was to establish the diagnostic precision of IOA in determining the need for surgical staging in grade 2 endometrioid endometrial carcinoma. METHODS: Two hundred twenty-two patients underwent IOA. Results were compared to the final pathology report. The accuracy of the IOA parameters was calculated. Variables were evaluated in patients with positive versus negative IOA. Overall and disease-free survivals were calculated according to IOA, lymphadenectomy, and nodal metastasis. RESULTS: IOA was positive in 80 patients. It showed an accuracy of 76.13% when compared with the postoperative assessment. The best individual parameter was myometrial invasion. Nodal metastasis was observed in 16 patients in the positive IOA group and 7 patients in the negative group. Patients with lymph node metastasis had a 5-year overall survival rate of 80.9%, whereas patients without metastasis had a 5-year overall survival rate of 97.9%. CONCLUSIONS: IOA is an adequate tool to identify high-risk patients in grade 2 endometrial carcinoma. Myometrial invasion is the individual parameter that yields the highest diagnostic precision.

Prognostic Significance of the MAD1L1 1673 G: A Polymorphism in Ovarian Adenocarcinomas.

BACKGROUND: Ovarian cancer is the most lethal gynecologic cancer. Although most patients respond adequately to the first-line therapy, up to 85% experience a recurrence of disease, which carries a poor prognosis. Mitotic arrest deficiency 1 is a protein that helps in the assembly of the mitotic spindle assembly checkpoint by preventing anaphase until all chromatids are properly aligned. A single-nucleotide polymorphism in the MAD1L1 gene is prevalent in patients with advanced epithelial ovarian cancer and alters the way in which it responds to chemotherapy. OBJECTIVE: The objective of the study was to study the relationship between the rs1801368 polymorphism of MAD1L1 and prognosis of ovarian adenocarcinoma. METHODS: A total of 118 patients in whom the MAD1L1 gene was sequenced were analyzed using descriptive and comparative statistics. RESULTS: Patients carrying the wild-type genotype had a higher distribution of early-stage disease. Having a MAD1L1 polymorphic allele increased the risk of being non-sensitive to chemotherapy. The median disease-free survival for patients with the wild-type MAD1L1 was 46.93 months, compared to 10.4 months for patients with at least one polymorphic allele. CONCLUSIONS: The rs1801368 polymorphism of MAD1L1 gene worsens prognosis in patients with ovarian adenocarcinoma. Traditional therapy for ovarian cancer might not be optimal in patients carrying this polymorphism.

Therapeutic use of human papillomavirus vaccines in cervical lesions

ABSTRACT Human papillomavirus (HPV) has been associated with the development of precancerous lesions of the cervix and cervical cancer (CC). Prophylactic HPV vaccination induces the development of a specific memory immune response that facilitates HPV elimination once the natural infection occurs. At present, in addition to the prophylactic vaccine, therapeutic vaccines are being developed and researched with the aim of inducing an immune response that allows the elimination of HPV-infected cells. The purpose of this study is to describe the current evidence on the use of therapeutic vaccines and their effect on cervical precancerous lesions, to establish recommendations on their clinical use. So far, the studies that have generated results have described a marginal beneficial effect of the prophylactic vaccine in the management of infection and pre-invasive lesions. Based on the evidence, continuing research on the efficacy and safety of therapeutic vaccines for the treatment of cervical intraepithelial lesions is recommended. The use of the HPV prophylactic vaccine as treatment for pre-existing lesions is not advised, but it is recommended to prevent new lesions.

Prognostic Significance of the MAD1L1 1673 G: A Polymorphism in Ovarian Adenocarcinomas.

BACKGROUND: Ovarian cancer is the most lethal gynecologic cancer. Although most patients respond adequately to the first-line therapy, up to 85% experience a recurrence of disease, which carries a poor prognosis. Mitotic arrest deficiency 1 is a protein that helps in the assembly of the mitotic spindle assembly checkpoint by preventing anaphase until all chromatids are properly aligned. A single-nucleotide polymorphism in the MAD1L1 gene is prevalent in patients with advanced epithelial ovarian cancer and alters the way in which it responds to chemotherapy. OBJECTIVE: The objective of the study was to study the relationship between the rs1801368 polymorphism of MAD1L1 and prognosis of ovarian adenocarcinoma. METHODS: A total of 118 patients in whom the MAD1L1 gene was sequenced were analyzed using descriptive and comparative statistics. RESULTS: Patients carrying the wild-type genotype had a higher distribution of early-stage disease. Having a MAD1L1 polymorphic allele increased the risk of being non-sensitive to chemotherapy. The median disease-free survival for patients with the wild-type MAD1L1 was 46.93 months, compared to 10.4 months for patients with at least one polymorphic allele. CONCLUSIONS: The rs1801368 polymorphism of MAD1L1 gene worsens prognosis in patients with ovarian adenocarcinoma. Traditional therapy for ovarian cancer might not be optimal in patients carrying this polymorphism.