The present review regarding atypical endometrial hyperplasia (AEH) focused on the main debated factors regarding this challenging clinical condition: (i) predictive variables of occult endometrial cancer (EC); (ii) the rate of EC underestimation according to different endometrial sampling methods; and (iii) the appropriateness of lymph node status assessment. When cancer is detected, approximately 90% of cases include low-risk EC, although intermediate/high-risk cases have been found in 10–13% of women with cancer. Older age, diabetes, high BMI, and increased endometrial thickness are the most recurrent factors in women with EC. However, the predictive power of these independent variables measured on internal validation sets showed disappointing results. Relative to endometrial sampling methods, hysteroscopic endometrial resection (Hys-res) provided the lowest EC underestimation, ranging between 6 and 11%. Further studies, including larger sample sizes of women undergoing Hys-res, are needed to confirm these findings. These data are urgently needed, especially for female candidates for conservative treatment. Finally, the evaluation of lymph node status measured on 660 of over 20,000 women showed a lymph node positivity of 2.3%. Although there has been an increase in the use of this procedure in AEH in recent years, the present data cannot recommend this option in AEH based on a cost/risk/benefit ratio.

Background: The rate of concurrent endometrial cancer (EC) in atypical endometrial hyperplasia (AEH) can be as high as 40%. Some patient characteristics showed associations with this occurrence. However, their real predictive power with related validation has yet to be discovered. The present study aimed to assess the performance of various models based on patient characteristics in predicting EC in women with AEH. Methods: This is a retrospective multi-institutional study including women with AEH undergoing definitive surgery. The women were divided according to the final histology (EC vs. no-EC). The available cases were divided into a training and validation set. Using k-fold cross-validation, we built many predictive models, including regressions and artificial neural networks (ANN). Results: A total of 193/629 women (30.7%) showed EC at hysterectomy. A total of 26/193 (13.4%) women showed high-risk EC. Regression and ANN models showed a prediction performance with a mean area under the curve of 0.65 and 0.75 on the validation set, respectively. Among the best prediction models, the most recurrent patient characteristics were age, body mass index, Lynch syndrome, diabetes, and previous breast cancer. None of these independent variables showed associations with high-risk diseases in women with EC. Conclusions: Patient characteristics did not show satisfactory performance in predicting EC in AEH. Risk stratification in AEH based mainly on patient characteristics may be clinically unsuitable.

This review aims to provide a comprehensive description of the clinical presentation, treatment, and histopathological features of extrauterine sites of leiomyomatosis (ESL), such as disseminated peritoneal leiomyomatosis (DPL), parasitic myoma (PM), benign metastatic leiomyoma (BML), and intravascular leiomyoma (IVL). The impact of previous surgery (hysterectomy or myomectomy) on development of intra-abdominal extrauterine leiomyomas (IAELs) and extra-abdominal extrauterine leiomyomas (EAELs) has been evaluated. According to PRISMA guidelines, we searched PubMed, Scopus, and Web of Science databases. Relevant articles were retrieved in full-text format and screened based on predefined inclusion and exclusion criteria. 358 studies (372 cases) are included. Among IAELs, the most common symptom is abdominopelvic pain (63.9% of DPL, and 69.2% of PMs cases, respectively). In contrast, EAELs exhibit heterogeneous clinical presentations; dyspnea is the most common symptom (29.7% of BML, and 29.9% of IVL cases, respectively). 68.8% of DPL, 60% of PM, 89.7% of BML, and 56.4% of IVL patients underwent previous uterine surgery. A significant association (p = 0.0417) between the type of previous uterine surgery (hysterectomy and myomectomy) and the subsequent location of ESLs is found (68.7% VS 51.4% in EAELs, 31.3% VS 48.6% in IAELs, respectively). DPL, PM, BML, and IVL exhibit overlapping characteristics, requiring a multimodal approach that includes imaging, histopathology, and surgical or medical management. Greater awareness among clinicians is needed regarding surgical procedures involving ligation and/or cutting of major uterine vessels, which appear to contribute to the development of EAELs, and morcellation, which tends to promote intraperitoneal metastatic spread.

HPV-independent cervical cancers represent a small proportion of these types of cancers, predominantly glandular lesions. It should be noted that some cases may depend on diagnostic problems that lead to false negative cases. However, the most recent classifications distinguish cervical tumors into HPV-associated and HPV-independent cancers. HPV-negative cervical carcinomas (5–11% of all cases) mainly include rare adenocarcinomas (gastric, mesonephric, clear, serous, and endometrioid) and present distinct clinical and molecular features. These tumors usually affect older women and are diagnosed at more advanced stages than HPV-positive tumors, with an overall worse prognosis. This concerning and notably worse prognosis highlights the need for further research and understanding. Unlike HPV-positive carcinomas (which depend on the viral oncogenes E6/E7), HPV-independent tumors accumulate genomic mutations that activate oncogenes and inactivate suppressor genes. Therefore, a comprehensive overview of these aspects can be the key to a better understanding and developing personalized treatments. In the present review, the main mutated genes, the signaling pathways involved, the differences from HPV-positive tumors, the distinctive immunohistochemical markers, and the diagnostic and therapeutic implications are explored in depth.

Cervical cancer (CC) is the only cancer that has the possibility of primary and secondary prevention. Despite this, it is one of the leading causes of cancer death among women, especially in developing countries. The World Health Organization has set the ambitious goal of eliminating CC by 2030 by suggesting specific types of intervention. Unfortunately, to date, we are very far from this goal at a global level, including developed countries. Implementing vaccination coverage among the target population is one of the strategies to be pursued in this area. Achieving this goal should include combating misinformation about the HPV vaccine, which is one of the main reasons for vaccination hesitancy. Such conspiracy theories are prevalent on social media, one of the primary sources of information for adults and adolescents today. In this regard, the Internet plays a significant role in disseminating information about the HPV vaccine, both positively and negatively. The Internet provides easy access to information about the HPV vaccine, including its safety, efficacy, recommended dosing schedule, and potential side effects. It may promote vaccine advocacy and debunking vaccine myths. On the other hand, the Internet may be the place for disseminating misinformation and influencing vaccine decision making. It is a double-edged sword in shaping public discourse and perceptions about the HPV vaccine. This overview aims to assess the literature on this topic in depth to promote evidence-based information, analyze the social channels through which misinformation spreads, and leverage digital health interventions essential for promoting HPV vaccination and reducing the burden of HPV-related diseases.

Pregnancies complicated by diabetes, including pregestational and gestational diabetes mellitus, are associated with increased maternal and fetal morbidity. Early identification of at-risk pregnancies is crucial for timely intervention and improved outcomes. Emerging evidence highlights the interplay of genetic predisposition, epigenetic modifications, and non-invasive biomarkers in the early detection of diabetic pregnancies. Genetic factors influencing insulin signaling, glucose metabolism, and pancreatic β-cell function may contribute to susceptibility to gestational hyperglycemia. Concurrently, epigenetic alterations, such as DNA methylation and histone modifications in maternal and placental tissues, have been linked to dysregulated metabolic pathways and adverse pregnancy outcomes. Non-invasive biomarkers, including circulating cell-free DNA and microRNAs in maternal blood, show promise for early diagnosis by offering a safer and more practical alternative to invasive testing. Integrating genetic, epigenetic, and molecular marker data could enhance risk stratification and enable personalized monitoring and management strategies. This review synthesizes current knowledge on the molecular underpinnings of diabetic pregnancies, evaluates the potential of emerging biomarkers for early diagnosis, and discusses the challenges and future perspectives for translating these findings into clinical practice. Understanding these mechanisms may pave the way for precision medicine approaches, ultimately improving maternal and neonatal outcomes in pregnancies affected by diabetes.