Medical Sciences

Identification and Computational Analysis of BRCA2 Variants in Mexican Women from Jalisco, Mexico, with Breast and Ovarian Cancer

Background: Breast and ovarian cancers (BC and OC) are prevalent malignancies in women globally, with germline variants in the BRCA2 gene significantly increasing the risk of developing these cancers. Despite extensive studies, the frequency and impact of BRCA2 variants in women from Jalisco, Mexico, remain underexplored. Objective: The aim of this study was to identify and characterize BRCA2 gene variants in Mexican women diagnosed with BC and OC and to assess their functional and structural consequences using computational analyses. Methodology: Genomic DNA from 140 Mexican women with BC and/or OC, selected based on clinical criteria suggestive of BRCA2 variants, was sequenced using NGS targeting BRCA2 coding regions. Functional effects were predicted with Ensembl VEP, SIFT, and PolyPhen-2. Structural impacts of missense variants were assessed using HOPE and AlphaFold models. Results: BRCA2 variants were identified in 12.86% of patients, with higher frequency in OC (21.05%) than BC (12%). Several mapped to key functional domains, including BRC repeats and the DNA-binding domain. Many were predicted as deleterious or probably damaging, though clinical classifications were often conflicting. Structural analysis indicated potential disruptions in protein stability or interactions for most missense variants. Clinically, BRCA2-positive BC patients were younger at diagnosis and showed a trend toward lower complete response. Conclusion: BRCA2 variants were found in 12.86% of patients, including six VUSs not reported in other populations. Several affected key functional domains with predicted deleterious effects. Findings support the need for genetic panels tailored to the Mexican population.

Survival Difference in Advanced-Stage Cervical and Ovarian Cancer Patients Treated with Concomitant Modulated Electro-Hyperthermia in Comparison to Classic Treatment Modalities: Results of a Pilot Study and Meta-Analysis

Background: Modulated electro-hyperthermia (mEHT) is one of the latest advancements in the field of oncological hyperthermia. Previous studies investigating mEHT revealed that it is safe and effective; however, no meta-analysis was conducted either in cervical or ovarian cancer. Methods: A single-institute pilot case series and a meta-analysis were conducted. Advanced stage cervical and ovarian cancer cases were included. In the pilot study, mEHT treatments were conducted using the Oncotherm EHY-2000+ and the EHY-2030 devices with 2–3 treatment sessions per week. Results: For the meta-analysis, a total of five studies were identified, with 160 and 31 cervical and ovarian cancer patients, respectively. In addition, 175 standard-of-care-treated cervical cancer patients were also identified as controls. The 1- and 2-year survival rate of the cervical cancer patients treated with mEHT was 87.61% [95% confidence interval (CI): 71.31–100%] and 78.13% (95% CI: 53.02–100%). Compared to the controls, the 2-year survival rates (78.13% vs. 58.86%) were significantly better in the mEHT-treated cohorts (odds ratio: 0.4143, p = 0.0441; hazard rate: 0.6607, p = 0.0103). The 1- and 2-year survival rates of ovarian cancer patients were 45.46% (95% CI: 5.97–84.95%) and 32.83% (95% CI: 0–79.57%), respectively. The result of our institutional data strengthened the results of the meta-analysis. Conclusions: Using mEHT, a significantly higher 2-year survival rate can be achieved in cervical cancer. In this setting, a wider testing/application of the modality is warranted. In the case of ovarian tumors, the available knowledge is minimal, and applicability and efficacy studies are urgently needed.

Is Night Shift Work Associated with Ovarian Cancer? A Systematic Review and Meta-Analysis

Background: Night shift work has been classified as a probable carcinogen due to its disruption of circadian rhythms. However, whether night shift work can increase the risk of ovarian cancer remains unclear. Herein, we investigated this association using a systematic review and meta-analysis. Methods: We systematically searched several databases until June 2025 for relevant studies. Effect estimates were extracted and pooled using a random-effects model to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity across studies was assessed using the I2 statistic, and publication bias was assessed using Egger’s regression test and funnel plot asymmetry. Results: Seven studies (eight cohorts) involving >2.5 million women were included. Overall, night shift work was not significantly associated with ovarian cancer (OR = 1.13; 95% CI: 0.96, 1.32; I2 = 49%). However, significant associations were observed in case–control studies (OR = 1.36; 95% CI: 1.12, 1.66; I2 = 0.8%) and in high-quality studies (OR = 1.17; 95% CI: 1.00, 1.37; I2 = 52%). Sensitivity analyses suggested that exposure misclassification in some cohort studies attenuated risk estimates. No publication bias was detected (z = −0.63, p = 0.53). Conclusions: While the overall findings did not demonstrate a statistically significant association, evidence from case–control studies that collected detailed information about night shift work suggests an increased ovarian cancer risk in night shift workers. Future large-scale prospective studies with detailed exposure assessments are warranted to confirm these findings.

Biologically-Based Notions About Uterine Bleeding During Myomectomy: Reasoning on Tradition and New Concepts

Uterine fibroids represent a prevalent category of tumors encountered in females of reproductive age, may present as singular or multiple entities and can manifest a variety of symptoms, which can negatively affect women’s daily lives. Pharmacological interventions may prove to be ineffective, occasionally costly, and associated with adverse effects. In instances where symptoms escalate in severity, myomectomy becomes a requisite as uterine-preserving operative therapy. Myomectomy can be performed utilizing laparoscopic, robotic, laparotomic, vaginal or hysteroscopic techniques. Given the abundant vascular supply to the myometrium, with blood being delivered to the uterus via the uterine arteries, myomectomy carries a considerable risk of significant hemorrhage during and subsequent to the surgical procedure, with the related complications. This paper aims to elucidate the conventional methodologies employed to mitigate hemorrhage during myomectomy and in the immediate postoperative phase, evaluating the effect of chemical interventions (such as vasopressin, octreotide, tranexamic acid, and uterotonics) alongside mechanical strategies (including uterine artery clamps, embolization, and tourniquets) to curtail bleeding during the myomectomy process. Furthermore, the potential of employing the intracapsular myomectomy technique without reliance on other traditional approaches was explored. This surgical method is grounded in the principles of the biological and anatomical characteristics of the fibroid, facilitating the enucleation of the myoma from its pseudocapsule. This anatomical entity, which is formed by the myoma throughout its development within the myometrium, enables the fibroid to be detached from the uterine musculature and supplies the requisite neurovascular support for its sustenance. Finally, the narrative review also shows how the intracapsular approach, which uses the fibroid’s biology, reduces bleeding during myomectomy.

Brenner Tumor of the Ovary: A 10-Year Single Institution Experience and Comprehensive Review of the Literature

Brenner tumors (BTs) are surface-epithelial stromal cell tumors that are categorized by the World Health Organization as benign, borderline, and malignant. Due to the rarity of BTs, the published literature on these tumors is comprised primarily of case reports and small retrospective studies. We performed a pathology database review spanning the last ten years at our institution revealing nine reported benign BTs. We collected the clinical and pathological data of patients associated with those BTs, describing the clinical presentation and imaging results, and assessing the possible risk factors associated with them. The average age at diagnosis was 58 years. BTs were discovered incidentally in 7/9 cases. The tumor was multifocal and bilateral in 1/9 cases and ranged in size from 0.2 cm to 7.5 cm. Associated Walthard rests were found in 6/9 cases and transitional metaplasia of surface ovarian and/or tubal epithelium was found in 4/9 cases. One patient had an associated mucinous cystadenoma in the ipsilateral ovary. Another patient had an associated mucinous cystadenoma in the contralateral ovary. In conclusion, we found that Walthard rests and transitional metaplasia are common findings in association with BTs. Additionally, pathologists and surgeons need to be aware of the association between mucinous cystadenomas and BTs.

Development of an Anthropomorphic Heterogeneous Female Pelvic Phantom and Its Comparison with a Homogeneous Phantom in Advance Radiation Therapy: Dosimetry Analysis

Background: Accurate dosimetry is crucial in radiotherapy to ensure optimal radiation dose delivery to the tumor while sparing healthy tissues. Traditional dosimetry techniques using homogeneous phantoms may not accurately represent the complex anatomical variations in cervical cancer patients, highlighting the need to compare dosimetry results obtained from different phantom models. Purpose: The aim of this study is to design and evaluate an anthropomorphic heterogeneous female pelvic (AHFP) phantom for radiotherapy quality assurance in cervical cancer treatment. Materials and method: Thirty RapidArc plans designed for cervical cancer patients were exported to both the RW3 homogeneous phantom and the anthropomorphic heterogeneous pelvic phantom. Dose calculations were performed using the anisotropic analytic algorithm (AAA), and the plans were delivered using a linear accelerator (LA). Dose measurements were obtained using a 0.6 cc ion chamber. The percentage (%) variation between planned and measured doses was calculated and analyzed. Additionally, relative dosimetry was performed for various target locations using RapidArc and IMRT treatment techniques. The AHFP phantom demonstrated excellent agreement between measured and expected dose distributions, making it a reliable quality assurance tool in radiotherapy. Results: The results reveal that the percentage variation between planned and measured doses for all RapidArc quality assurance (QA) plans using the AHFP phantom is 10.67% (maximum value), 2.31% (minimum value), and 6.89% (average value), with a standard deviation (SD) of 2.565 (t = 3.21604, p = 0.001063). Also, for the percentage of variation between homogeneous and AHFP phantoms, the t-value is −11.17016 and the p-value is <0.00001. The result is thus significant at p < 0.05. We can see that the outcomes differ significantly due to the influence of heterogeneous media. Also, the average gamma values in RapidArc plans are 0.29, 0.32, and 0.35 (g ≤ 1) and IMRT plans are 0.45, 0.44, and 0.42 (g ≤ 1) for targets 1, 2, and 3, respectively. Conclusion: The AHFP phantom results show more dose variability than homogenous phantom outcomes. Also, the AHFP phantom was found to be suitable for QA evaluation.

The Role of Delayed Interval Debulking Surgery (DIDS) in the Surgical Treatment of Advanced Epithelial Ovarian Cancer: A Retrospective Cohort from an ESGO-Certified Center

Background/Objectives: Patients with advanced ovarian cancer with a high tumor burden typically undergo neoadjuvant chemotherapy (NACT) followed by interval debulking surgery. The optimal number of NACT cycles remains undefined: although three to four cycles are considered gold-standard, in real-world practice, five or more cycles are frequently administrated. This study aims to evaluate the impact of delayed interval debulking surgery (DIDS) after ≥5 cycles of NACT on the survival rates. Methods: We conducted a retrospective analysis of women with advanced ovarian cancer that underwent surgery in the 1st Department of Obstetrics–Gynecology Clinic from 2012 to 2022. Patient characteristics, oncological, and follow-up information were collected. Results: A total of 125 patients met the inclusion criteria and were divided into two groups: Group A (77 patients) received 3–4 of NACT cycles, and Group B (48 patients) ≥5 cycles. No statistically significant difference was observed between the groups concerning age, BMI, comorbidities, Aletti score, FIGO stage, pre-operative CA-125 values, surgery duration, rate of postoperative complications, hospital stay, ICU admittance, and complete gross resection (RD = 0). However, patients undergoing DIDS experienced significantly greater intraoperative blood loss. Progression-free survival did not differ between groups (IDS: 17 vs. DIDS: 18 months, p = 0.561), whereas overall survival was significantly lower in the DIDS group (IDS: 52 vs. DIDS: 36 months, p = 0.00873). This statistical significance persisted after controlling for residual disease, but was lost after adjusting for FIGO stage. Conclusions: DIDS may be considered for advanced ovarian cancer patients with a high tumor burden, when complete gross resection (RD = 0) cannot be achieved during IDS. Further prospective randomized trials are necessary to evaluate its oncological safety and morbidity.

Difluoromethylornithine (DFMO) Enhances the Cytotoxicity of PARP Inhibition in Ovarian Cancer Cells

Ovarian cancer accounts for 3% of the total cancers in women, yet it is the fifth leading cause of cancer deaths among women. The BRCA1/2 germline and somatic mutations confer a deficiency of the homologous recombination (HR) repair pathway. Inhibitors of poly (ADP-ribose) polymerase (PARP), another important component of DNA damage repair, are somewhat effective in BRCA1/2 mutant tumors. However, ovarian cancers often reacquire functional BRCA and develop resistance to PARP inhibitors. Polyamines have been reported to facilitate the DNA damage repair functions of PARP. Given the elevated levels of polyamines in tumors, we hypothesized that treatment with the polyamine synthesis inhibitor, α-difluoromethylornithine (DFMO), may enhance ovarian tumor sensitivity to the PARP inhibitor, rucaparib. In HR-competent ovarian cancer cell lines with varying sensitivities to rucaparib, we show that co-treatment with DFMO increases the sensitivity of ovarian cancer cells to rucaparib. Immunofluorescence assays demonstrated that, in the presence of hydrogen peroxide-induced DNA damage, DFMO strongly inhibits PARylation, increases DNA damage accumulation, and reduces cell viability in both HR-competent and deficient cell lines. In vitro viability assays show that DFMO and rucaparib cotreatment significantly enhances the cytotoxicity of the chemotherapeutic agent, cisplatin. These results suggest that DFMO may be a useful adjunct chemotherapeutic to improve the anti-tumor efficacy of PARP inhibitors in treating ovarian cancer.

Novel Vaccine Strategies and Factors to Consider in Addressing Health Disparities of HPV Infection and Cervical Cancer Development among Native American Women

Cervical cancer is the 4th most common type of cancer in women world-wide. Many factors play a role in cervical cancer development/progression that include genetics, social behaviors, social determinants of health, and even the microbiome. The prevalence of HPV infections and cervical cancer is high and often understudied among Native American communities. While effective HPV vaccines exist, less than 60% of 13- to 17-year-olds in the general population are up to date on their HPV vaccination as of 2020. Vaccination rates are higher among Native American adolescents, approximately 85% for females and 60% for males in the same age group. Unfortunately, the burden of cervical cancer remains high in many Native American populations. In this paper, we will discuss HPV infection, vaccination and the cervicovaginal microbiome with a Native American perspective. We will also provide insight into new strategies for developing novel methods and therapeutics to prevent HPV infections and limit HPV persistence and progression to cervical cancer in all populations.

US Cancer Screening Recommendations: Developments and the Impact of COVID-19

The USPSTF and ACS recommend screening for breast, cervical, colorectal, and lung cancers. Rates of cancer screening, diagnosis, and treatment decreased significantly in the US and other developed nations during the height of the COVID-19 pandemic and lockdown (April 2020) and have since recovered, although not to baseline levels in many cases. For breast cancer, the USPSTF recommends biennial screening with mammography for women aged 50–74, while the ACS recommends annual screening for women aged 45–54, who may transition to biennial after 55. Minority and rural populations have lower rates of screening and lower utilization of DBT, which offers superior sensitivity and specificity. Among 20 US health networks in April 2020, mammography rates were down 89.2% and new breast cancer diagnoses down by 50.5%. For cervical cancer, the USPSTF recommends cervical cytology every three years for women 21–65, or cytology+hrHPV co-testing every five years for women aged 30–65. Cervical cancer screening rates declined by 87% in April 2020 and recovered to a 40% decline by June 2020, with American Indians and Asians most severely affected. For colorectal cancer (CRC), the USPSTF and ACS recommend screening for ages 45–75, recently lowered from a starting age of 50. Most commonly-used modalities include annual FIT testing, FIT+DNA testing every three years, and colonoscopy every ten years, with shorter repeat if polyps are found. In the US, CRC screenings were down by 79–84.5% in April 2020 across several retrospective studies. Patient encounters for CRC were down by 39.9%, and a UK-based model predicted that 5-year-survival would decrease by 6.4%. The USPSTF recommends screening low dose CT scans (LDCTs) for ages 50–80 with a >20 pack-year smoking history who have smoked within the past 15 years. In April 2020, screening LDCTs fell by 72–78% at one US institution and lung cancer diagnoses were down 39.1%.

A Deep Learning Approach for Classifying Benign, Malignant, and Borderline Ovarian Tumors Using Convolutional Neural Networks and Generative Adversarial Networks

Background/Objectives: Accurate preoperative characterization of ovarian masses is essential for appropriate clinical management, particularly for borderline ovarian tumors (BOTs), which are less common and often difficult to distinguish from benign or malignant lesions on ultrasound. Although expert subjective ultrasound assessment achieves high diagnostic accuracy, limited availability of highly trained sonologists restricts its widespread application. Artificial intelligence-based approaches offer a potential solution; however, the low prevalence of BOTs restricts the development of robust deep learning models due to severe class imbalance. This study aimed to develop a Convolutional Neural Network (CNN)-based classifier enhanced with Generative Adversarial Networks (GANs) to improve the discrimination of ovarian masses as benign, malignant, or BOT using ultrasound images. Methods: A total of 3816 ultrasound images from 636 ovarian masses were retrospectively analyzed, including 390 benign lesions, 202 malignant tumors, and 44 BOTs. To address class imbalance, a Deep Convolutional GAN (DCGAN) was used to generate 2000 synthetic BOT images for data augmentation. A three-class ensemble CNN model integrating VGG16, ResNet50, and InceptionNetV3 architectures was developed. Performance was assessed on an independent test set and compared with a baseline model trained without DCGAN augmentation. Results: The incorporation of DCGAN-generated BOT images significantly enhanced classification performance. The BOT F1-score increased from 68.4% to 86.5%, while overall accuracy improved from 84.7% to 91.5%. For BOT identification, the final model achieved a sensitivity of 88.2% and specificity of 85.1%. Class-specific AUCs were 0.96 for benign lesions, 0.94 for malignant tumors, and 0.91 for BOTs. Conclusions: DCGAN-based augmentation effectively expands limited ultrasound datasets and improves CNN performance, particularly for BOT detection. This approach demonstrates potential as a decision support tool for preoperative assessment of ovarian masses.