Background: Endometrial cancer (EC) is the most common gynecological malignancy, increasingly affecting premenopausal women. While hysterectomy is the standard treatment, it eliminates reproductive potential, highlighting the need for effective fertility-sparing alternatives. Current ESHRE/ESGO/ESGE guidelines recommend progestin-based therapies, often with hysteroscopic resection. However, these are based on limited pharmacological options and moderate to low-quality evidence. Novel and combination therapies have shown promise but remain absent from current clinical guidelines. This review aims to evaluate the efficacy and safety of fertility-preserving treatments for early-stage EC, emphasizing the need to update current strategies based on emerging data. Methods: A systematic review and meta-analysis will follow PRISMA guidelines and the Cochrane Handbook. Eligible studies, including randomized and non-randomized designs, will assess fertility-preserving treatments for early-stage EC. Data will be extracted on complete response, recurrence, and long-term fertility outcomes. The GRADE system will assess evidence certainty. Risk of bias will be evaluated using RoB 2 for RCTs and ROBINS-I for non-randomized studies. Meta-analysis will be performed if sufficient data are available. Conclusions: This review will provide a comprehensive analysis of fertility-sparing treatments for early-stage EC, support personalized strategies, identify evidence gaps, and guide future research. Trial registration—Prospero: CRD420251032161.

Background: Atypical endometrial hyperplasia is a precursor of endometrial carcinoma, increasingly diagnosed in reproductive-aged women. Standard hysterectomy may constitute overtreatment. Fertility-sparing approaches, oral or local progestins, hysteroscopic resection, and combined regimens are widely used, though evidence largely derives from early-stage carcinoma. Methods: CENTRAL, EMBASE, Scopus, Web of Science, and PubMed were searched from inception to 13 April 2025. Eligible studies included premenopausal women with AEH treated with oral progestins, levonorgestrel intrauterine devices (LNG-IUDs), hysteroscopic resection, or combination regimens (e.g., oral progestins + metformin, LNG-IUD + GnRH analogues). Random-effects meta-analyses with multilevel modeling were applied. Risk of bias was assessed using RoB-2 and ROBINS-I; certainty of evidence was graded with GRADE-PRO. Results: Forty-nine studies (2313 women) were included. The pooled complete response (CR) rate was 85% (95% CI 80–89%). LNG-IUDs resulted in 88% CR and oral progestins in 80%. Combination therapies achieved up to 95% CR, though data were limited. Hysteroscopic resection combined with hormonal therapy reported high CR rates (96–97%) but relied on small, heterogeneous cohorts with uncertain reproducibility. The pooled recurrence rate was 19% (95% CI, 13–25%), lower with LNG-IUDs (14%) compared with oral progestins (22%). No response occurred in 14% overall and was lower with LNG-IUDs (13%) than oral progestins (19%). Among women attempting conception, the pooled pregnancy rate was 41%, and the live birth rate was 30%. The mean time to achieve CR was 5.6 months, whereas the mean time to recurrence was approximately 33 months. Conclusions: LNG-IUDs provide the most effective and well-supported fertility-sparing treatment for AEH, ensuring high remission with low recurrence. Despite favorable numerical outcomes, the evidence for hysteroscopic resection is limited and inconsistent, not supporting its routine use. Combination regimens may improve response but require confirmation in larger studies.

Endometrial carcinoma (EC) is the leading gynecologic malignancy in high-income countries, with a consistent upward trend in incidence observed among younger women, particularly in those younger than 50 years

Objective: To evaluate the level of knowledge, attitudes, and practices of Hungarian general practitioners (GPs) concerning human papillomavirus (HPV) infection, cervical cancer prevention, and HPV vaccination, and to identify physician-level factors associated with proactive recommendation practices. Methods: A cross-sectional nationwide survey was conducted between 30 April and 1 June 2024. The online questionnaire was distributed to practicing Hungarian GPs listed in the National Health Insurance Fund database. Anonymous responses were collected on demographic data, knowledge of HPV transmission and oncogenic potential, awareness of vaccination guidelines, and clinical counseling habits. Descriptive and inferential statistical analyses were performed. A total of 413 responses were received. Results: Most respondents were female (72.6%) with an average of 22.4 ± 9.6 years of professional experience. Although 89.8% correctly identified the causal link between HPV and cervical cancer, only 56.2% were aware of the complete vaccination schedule recommended for adolescents initiating after age 15. Knowledge scores were significantly higher among female physicians, urban practitioners, and those with postgraduate preventive medicine training. While the overall attitude toward HPV vaccination was positive (mean 4.6/5), 38.4% of respondents reported parental hesitancy as a common barrier, often citing misinformation regarding vaccine safety (64.9%) and lack of perceived need for boys (58.7%). Regression analysis revealed that familiarity with WHO and national vaccination guidelines independently predicted proactive vaccine recommendation (β = 0.43, p < 0.001). Conclusions: Hungarian general practitioners demonstrate good baseline awareness of HPV and its oncogenic role; however, knowledge gaps persist regarding vaccination schedules and counseling practices. Enhancing continuous medical education and communication training could strengthen GPs’ role as key advocates in HPV vaccine promotion.

The objective of this study is to evaluate the systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) in relation to lymph node metastasis, lymphovascular space invasion (LVSI), tumor size, stromal invasion depth, and p16/p53 status in vulvar squamous cell carcinoma. This retrospective single-center cohort study included 92 patients treated between January 2017 and March 2026. SII and SIRI were calculated from routine complete blood counts. Associations were assessed using non-parametric tests and multivariable logistic regression. Receiver operating characteristic analysis evaluated discrimination, expressed as the area under the curve (AUC), with paired DeLong comparison of the two indices. Incremental predictive value was assessed by nested logistic regression, with internal validation using 2000 bootstrap resamples. Both indices were higher in patients with lymph node metastasis and LVSI and correlated positively with tumor size, but not with stromal invasion depth or p16/p53 status. Discrimination was moderate and similar for lymph node metastasis (AUC, 0.670 vs 0.653; paired DeLong, p = 0.679) and for LVSI (0.733 vs 0.732; p = 0.964). In the cutoff-based multivariable model, elevated SIRI remained independently associated with lymph node metastasis (adjusted odds ratio, 4.30; 95% confidence interval, 1.51–12.27; p = 0.006), whereas elevated SII did not. Adding continuous SIRI to a clinicopathological base model improved neither fit (p = 0.159) nor discrimination (AUC difference, 0.013; p = 0.716). SII and SIRI were associated with adverse pathological features, but their discriminatory performance did not differ significantly, and SIRI provided no significant incremental predictive value beyond the clinicopathological base model. These indices should be considered exploratory adjunctive biomarkers requiring external validation. Graphical Abstract

Background: Prognosis in vulvar squamous cell carcinoma (VSCC) is strongly influenced by lymph node involvement and adverse clinicopathological features. Systemic inflammatory indices derived from blood counts may reflect tumor–host interactions associated with adverse pathological phenotypes. Objective: To assess associations of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) with nodal metastasis, lymphovascular space invasion (LVSI), and tumor size. Methods: This retrospective single-center study included 93 surgically treated patients between March 2017 and February 2026. Results: NLR was associated with nodal metastasis (unadjusted p = 0.015; false discovery rate [FDR]-adjusted q = 0.047) and LVSI (unadjusted p < 0.001; FDR-adjusted q = 0.006). NLR showed modest discrimination for nodal metastasis (area under the receiver operating characteristic curve [AUC] = 0.647). For LVSI, NLR had the highest AUC among the evaluated markers (AUC = 0.789; 95% confidence interval [CI]: 0.683–0.894), but 16 cases were positive and the positive predictive value (PPV) was low (0.378). Nominal MLR findings for LVSI and large tumor size did not remain significant after FDR correction (both q = 0.308), while PLR showed no consistent associations. Elevated NLR was associated with nodal metastasis in univariable analysis (odds ratio [OR] = 3.291; p = 0.012) but not in multivariable models including LVSI (adjusted OR = 1.296; p = 0.654) or excluding LVSI (adjusted OR = 1.823; p = 0.261). Conclusions: NLR was associated with adverse pathological features but was not independently associated with nodal metastasis and should not be used as a standalone predictive or clinical decision-making tool.