Endometrial cancer (EC) incidence is rising, particularly among younger women, with significant disparities observed across different racial and ethnic groups. A study highlighted that early-onset endometrial cancer (EOEC), diagnosed in women under 50, has increased in prevalence, contrasting with trends in late-onset cases. This increase is particularly pronounced among certain demographics, indicating a need for targeted public health strategies to address these disparities (ref: Liu doi.org/10.1093/jncics/). Furthermore, the relationship between obesity and endometrial cancer risk is underscored by findings that metabolically unhealthy obesity significantly elevates the risk for various obesity-related cancers, including endometrial cancer, with hazard ratios ranging from 2.55 to 3.00 (ref: Sun doi.org/10.1093/jnci/). Additionally, individuals with type 2 diabetes exhibit a 1.5-fold increased risk of endometrial cancer mortality, emphasizing the intersection of metabolic health and cancer outcomes (ref: Ling doi.org/10.1007/s00125-022-05854-8/). Risk prediction models developed from a large international consortium have shown modest improvements in discrimination when genetic factors are included, suggesting that while epidemiological factors are crucial, genetic insights may enhance predictive accuracy (ref: Shi doi.org/10.1093/jnci/). Overall, these findings highlight the multifaceted nature of endometrial cancer risk, necessitating a comprehensive approach to prevention and early detection.

The molecular underpinnings of endometrial cancer are increasingly understood, particularly regarding genetic predispositions such as Lynch syndrome, which accounts for a significant proportion of endometrial cancer cases. Recent advancements have clarified the genetic basis of Lynch syndrome, revealing its association with DNA mismatch repair deficiencies and the implications for immunotherapy in treating advanced cancers (ref: Peltomäki doi.org/10.1053/j.gastro.2022.08.058/). Additionally, mutations in the SPOP gene have been linked to endometrial cancer, with studies indicating that these mutations disrupt normal cellular processes, contributing to tumorigenesis (ref: Cuneo doi.org/10.1016/j.molcel.2022.12.033/). The exploration of novel therapeutic strategies, such as DNA dendron vaccines, aims to enhance immune responses against cancer cells, showcasing the potential for innovative treatment modalities (ref: Distler doi.org/10.1073/pnas.2215091120/). Moreover, a comprehensive analysis of hereditary cancer risk across a large cohort has provided insights into the prevalence of various genetic mutations and their associated cancer risks, underscoring the importance of genetic screening in cancer prevention (ref: Cummings doi.org/10.1200/PO.22.00415/). Together, these studies illustrate the critical role of genetic factors in the pathogenesis of endometrial cancer and the ongoing efforts to translate these findings into clinical practice.

Recent guidelines for the treatment of endometrial cancer have been adapted to reflect regional practices, particularly in Asia, where variations in management strategies necessitate tailored approaches (ref: Koppikar doi.org/10.1016/j.esmoop.2022.100774/). The integration of advanced imaging techniques, such as magnetic resonance imaging-guided adaptive brachytherapy, has shown promising results in reducing severe morbidity associated with treatment, with a reported 5-year actuarial estimate for organ-related events at 18.4% (ref: Vittrup doi.org/10.1016/j.ijrobp.2023.01.002/). Additionally, the safety and tolerability of postoperative proton beam therapy have been evaluated, indicating low rates of acute and late toxicities, thus presenting a viable option for patients with endometrial cancer (ref: Arians doi.org/10.1016/j.ijrobp.2023.01.004/). Furthermore, studies have demonstrated that higher surgical volumes at hospitals correlate with improved survival outcomes in early-stage cervical cancer, suggesting that surgical expertise plays a crucial role in treatment efficacy (ref: Bizzarri doi.org/10.1097/AOG.0000000000005026/). These findings emphasize the importance of optimizing treatment protocols and ensuring access to high-quality surgical care for better patient outcomes.

Cervical cancer and endometrial cancer share several risk factors and biological mechanisms, particularly in the context of hormonal influences and genetic predispositions. Recent studies utilizing single-cell transcriptomic analysis have provided insights into the cellular environments of endometriosis, a condition associated with both cervical and endometrial cancers, revealing distinct cellular signatures that may contribute to cancer development (ref: Fonseca doi.org/10.1038/s41588-022-01254-1/). Additionally, research into the effects of radiochemotherapy on cervical cancer has shown that treatment not only targets malignant cells but also induces significant immune responses, which could inform strategies for managing endometrial cancer (ref: Liu doi.org/10.1038/s41392-022-01264-9/). The impact of the COVID-19 pandemic on cervical cancer screening participation has highlighted the vulnerabilities in cancer care systems, with significant declines in screening rates observed, which could have downstream effects on early detection of related cancers (ref: Olesen doi.org/10.7554/eLife.81522/). Furthermore, disparities in screening coverage across sub-Saharan Africa underscore the need for improved access to preventive services, particularly for women living with HIV, who face heightened risks for both cervical and endometrial cancers (ref: Yang doi.org/10.1371/journal.pmed.1004143/). These interconnected findings illustrate the complex relationship between cervical and endometrial cancers and the necessity for integrated approaches in research and public health.

Screening and early detection strategies for gynecological cancers, particularly cervical cancer, have been significantly impacted by recent global health challenges. A systematic analysis of cervical cancer screening coverage in sub-Saharan Africa revealed persistent disparities, with screening rates remaining stagnant in some regions despite the high burden of disease (ref: Yang doi.org/10.1371/journal.pmed.1004143/). The COVID-19 pandemic further exacerbated these challenges, as evidenced by a marked decline in screening participation in Denmark, where pre-pandemic participation rates dropped significantly during the initial lockdown phases (ref: Olesen doi.org/10.7554/eLife.81522/). Additionally, research into cervical cancer screening practices within U.S. prisons highlighted systemic barriers that hinder access to timely screening and follow-up care, emphasizing the need for targeted interventions to improve health outcomes in marginalized populations (ref: Kanbergs doi.org/10.1016/j.amepre.2022.09.021/). The Onclarity trial's findings on the efficacy of extended genotyping for detecting high-grade cervical neoplasia further underscore the importance of advancing screening technologies to enhance early detection and treatment outcomes (ref: Stoler doi.org/10.1016/j.ygyno.2023.01.004/). Collectively, these studies highlight the critical need for improved screening strategies and equitable access to care to effectively combat gynecological cancers.

The role of immunotherapy in the treatment of endometrial cancer is gaining traction, particularly with the endorsement of guidelines for mismatch repair (MMR) and microsatellite instability (MSI) testing to identify patients who may benefit from immune checkpoint inhibitors (ref: Vikas doi.org/10.1200/JCO.22.02462/). Recent studies have demonstrated the feasibility of noninvasive detection of MSI in endometrial cancer patients using droplet-digital PCR, achieving a high concordance rate with traditional methods, thus providing a promising avenue for monitoring disease progression (ref: Casas-Arozamena doi.org/10.1002/ijc.34435/). Additionally, the exploration of circRNA's role in lymph node metastasis has revealed potential therapeutic targets, as circVPRBP was found to inhibit lymphangiogenesis and metastasis in cervical cancer models (ref: Zhang doi.org/10.1038/s41388-023-02595-9/). These findings highlight the evolving landscape of biomarker research and immunotherapy in endometrial cancer, suggesting that integrating molecular diagnostics into clinical practice could enhance personalized treatment approaches.

Socioeconomic disparities significantly impact cancer care, particularly in the context of fertility-sparing treatments for women diagnosed with cervical, endometrial, or ovarian cancers. A population-based study revealed that clinical and sociodemographic factors contribute to unequal access to fertility preservation options, underscoring the need for policies that address these disparities (ref: Jorgensen doi.org/10.1097/AOG.0000000000005044/). Furthermore, the uptake of the HPV vaccine, a critical preventive measure against cervical cancer, remains inconsistent, with healthcare provider recommendations being a strong predictor of vaccination rates (ref: Boitano doi.org/10.1097/AOG.0000000000005056/). Additionally, research indicates that trans masculine individuals face higher rates of unsatisfactory Pap tests, which may hinder early detection of cervical cancer, highlighting the need for tailored screening approaches to accommodate diverse populations (ref: Wang doi.org/10.1089/lgbt.2021.0400/). These findings emphasize the importance of addressing socioeconomic and demographic factors in cancer prevention and treatment strategies to ensure equitable healthcare access for all patients.