Broadly neutralizing antibodies (bNAbs) are a promising HIV prevention strategy due to their potent antiviral activity and potential for long-acting protection. While the vaginal microbiome can influence mucosal immunity and the efficacy of topical interventions, its effect on the pharmacokinetics of systemically administered bNAbs remains unclear. Forty-two women were included in a retrospective analysis of the CAPRISA 012B clinical trial evaluating passive immunization for HIV prevention. Vaginal microbiota were profiled using 16 S rRNA gene sequencing and classified into three community state types (CSTs): CST I (Lactobacillus crispatus-dominated), CST III (Lactobacillus iners-dominated), and CST IV (diverse, non-Lactobacillus-dominated). Mucosal concentrations of CAP256V2LS were measured from Soft-cup® cervicovaginal fluid using the Meso Scale Discovery (MSD) platform with electrochemiluminescence (ECL) detection. Longitudinal analyses assessed CST stability, transitions, and associations with mucosal antibody pharmacokinetics. Lactobacillus-dominated CSTs were most frequent (CST I, 5.3%; CST III, 57.9%), whereas BV-associated CST IV subtypes were less common (CST IV-A, 2.6%; CST IV-B, 34.2%). Lactobacillus-dominated communities were generally stable, while high-diversity CST IV communities were more dynamic, with transitions toward Lactobacillus-dominated states observed over time. Despite these microbial shifts, mucosal bNAb kinetic patterns appeared broadly similar across CSTs. Within the limits of this exploratory analysis, we did not observe clear evidence of an association between CST composition and the timing or magnitude of mucosal bNAb accumulation. These observations were descriptive and not derived from inferential statistical or pharmacokinetic modelling analyses. In this exploratory sub-analysis, cervicovaginal microbiome composition was not clearly associated with differences in mucosal concentrations of systemically administered bNAbs. These findings suggest that systemic bNAb delivery may achieve measurable genital tract exposure across diverse vaginal microbial communities; however, larger studies incorporating inferential pharmacokinetic and immunological analyses are needed to confirm these observations and exclude subtle microbiome-associated effects.

Patients with co-existent endometrial and ovarian carcinoma (CEOC) have been shown to have an excellent prognosis if their tumors meet the FIGO 2023 endometrial carcinoma (EC) stage IA3 criteria. In addition, excluding the intermediate and high-risk molecular subtypes (mismatch repair deficient [MMRd], p53 abnormal [p53abn], and No Specific Molecular Profile [NSMP] ER-low/negative) has been recently shown to improve risk stratification in CEOCs. In contrast, co-existent EC with fallopian tube (FT) involvement is considered pathologic T3/FIGO stage III. Our objective was to assess whether the FIGO 2023 IA3 criteria for CEOC can identify a subset of patients with coexistent endometrial and FT carcinoma at low risk of recurrence and if incorporation of molecular features can aid in prognostic stratification. An institutional database search was carried out at 2 institutions to identify T3a EC with FT involvement. Cases with nodal, pelvic side wall, vaginal, parametrial, adnexal soft tissue or peritoneal involvement, or treatment with neoadjuvant therapy were excluded. A total of 71 patients were identified. Fourteen carcinomas recurred (14/71: 19.7%); of these 85.7% (12/14) were endometrioid FIGO grade 3 or non-endometrioid histotypes, and 85.7% (12/14) had intermediate or adverse molecular features. Eight (8/71: 11.3%) carcinomas met the FT-adapted FIGO 2023 IA3 criteria with no recurrences. Further modifying the criteria by excluding tumors with adverse molecular features while expanding the pathology criteria to include ovarian and/or bilateral adnexal involvement identified 11/71 patients (15.5%), none of whom experienced a recurrence. By adapting the FIGO 2023 criteria for low-risk CEOCs to assess co-existent endometrial and FT carcinomas, we identified a subset of patients with excellent outcomes, such that treatment de-escalation could be considered. Furthermore, it may be possible to expand this category of low-risk co-existent endometrial and FT carcinoma, based on refined molecular/pathological features, so more patients with uterus/adnexa confined carcinoma and indolent disease behavior can be identified.

The first national HPV-based cervical screening programs began in 2017. Since then, a growing list of countries have moved, or want to move, to HPV-based screening. One of the benefits of HPV-based screening is that a sample does not need to be collected from the cervix by a healthcare practitioner. Self-collection has been demonstrated to give equivalent accuracy as practitioner-collected specimens when a PCR-based clinically validated HPV assay is used. However, there are few clinically validated, PCR-based, HPV assays with on-label claims for self-collection. The current study, Self-Collection or Practitioner-collection Evaluation 2 (SCoPE2), undertook a VALHUDES protocol evaluation with individuals recruited in a colposcopy population in the context of an HPV-based screening program. SCoPE2 recruited 400 participants who each took a self-collected vaginal sample using a FLOQSwab. A practitioner-collected cervical sample was then collected at colposcopy. HPV testing was performed using both the cobas 4800 and the cobas HPV tests. The self-collected specimens demonstrated equivalent and non-inferior relative sensitivity for histologically confirmed CIN2+ (n = 58) when compared with the practitioner-collected specimen for both the cobas 4800 (0.982) and cobas (1.037), but relative specificity was inferior. Additional analyses were undertaken to resolve referral, self-, and practitioner-collected discordant results. SCoPE2 demonstrates that the assessed self-collection method is non-inferior for the detection of CIN2+ when compared with a practitioner-collected specimen.

Gynecological cancers, encompassing malignancies of the cervix, vagina, uterus, fallopian tubes, and ovaries, remain a significant global health burden despite advances in cancer therapeutics and epidemiological trends. According to the International Agency for Research on Cancer (IARC), these neoplasms account for approximately 19% of nearly 5 million new cancer cases and 3 million deaths annually, disproportionately impacting women in low- and middle-income countries. Traditional diagnostic approaches, including histological tumor biopsies, play a critical role in cancer classification and molecular characterization; however, such invasive procedures pose limitations related to patient suitability, procedural risks, and sampling biases due to tumor heterogeneity. This scenario highlights the urgent need for innovative, minimally invasive diagnostic modalities capable of early detection and personalized disease management. Liquid biopsy has emerged as a promising noninvasive alternative, harnessing circulating tumor-derived biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), tumor-educated platelets (TEPs), extracellular vesicles (EVs), and circulating RNAs. Since the first identification of ctDNA in female-specific malignancies in 2012, there have been substantial technological advances over the past decade that underscore the clinical potential of liquid biopsies in gynecological oncology. These circulating biomarkers provide dynamic insights into tumor genetics and heterogeneity, facilitating early diagnosis, prognostication, and real-time monitoring while circumventing the limitations of tissue biopsies. This review highlights current evidence on liquid biopsy applications for gynecological cancers, focusing on recent methodological progress, biomarker validation, and diagnostic utility. Furthermore, it addresses existing challenges related to sensitivity, specificity, and standardization, emphasizing the translational prospects of liquid biopsy in enhancing personalized management and improving clinical outcomes for women afflicted with gynecological malignancies.

Based on finite element analysis (FEA), this study compared the effects of vaginal pessaries of different shapes and sizes on pelvic floor biomechanics in a patient with cystocele, providing a theoretical basis for clinical selection of pessaries. Pelvic floor finite element models were constructed using the patient's magnetic resonance images (MRI) data to simulate the conditions of wearing ring and Gellhorn pessaries, and the biomechanical parameters of pelvic organs were analyzed. After pessary insertion, bladder neck displacement (BND), uterine neck displacement (UND), and anterior vaginal wall (AVW) values decreased, and pelvic floor levator ani muscle (LAM), cardinal ligament (CL), and uterosacral ligament (USL) stresses were reduced, along with lower contact pressures. Bladder pressure and intravesical fluid flow velocity became more stable. The Gellhorn pessary outperformed the ring pessary in limiting displacement and reducing ligament stress, but it was prone to creating localized high-pressure zones; the ring pessary exhibited lower tissue contact pressure and a more stable urinary flow environment. A size that is too small may result in insufficient support, while a size that is too large may increase the risk of mucosal injury. The biomechanical mechanisms of the two vaginal pessaries differ; clinical selection requires comprehensive consideration of the degree of prolapse, tissue tolerance, and urodynamic characteristics. The finite element model provides an effective evaluation framework for moving beyond empirical selection of vaginal pessaries and achieving individualized fitting.

Genital herpes, caused by herpes simplex virus 2 (HSV-2), remains a prevalent sexually transmitted infection with no available vaccine. Effective local immunity, mediated in part by tissue-resident memory T cells (TRM cells) and luminal antibodies, provides immediate viral control. Here, we developed bioactive enhanced adjuvant chemokine oligonucleotide nanoparticles (BEACONs) formed via electrostatic interactions between CpG oligodeoxynucleotides (CpG ODNs) and the chemokine CXCL9. This adjuvant enhances antigen-presenting cell engagement and innate immune signaling, promotes CD8 T cell recruitment, and reduces local neutrophilic inflammation relative to CpG ODNs. After intramuscular priming with HSV-2 glycoprotein-encoding messenger RNA-lipid nanoparticles, vaginal boosting with cognate recombinant glycoprotein and BEACONs improved protection against HSV-2 by increasing local CD8 TRM cell populations and mucosal antibody responses. Vaccine-mediated protection required local delivery of both antigen and adjuvant and was reduced by CD8 T cell or B cell depletion. These findings support engineered mucosal adjuvants for vaccines targeting genital herpes and other sexually transmitted infections.

Currently, live biotherapeutic products (LBP) have been widely used to improve gut microbiota, enhance immunity, and promote digestion. Engineering bacteria, as one form of LBP, have made breakthrough progress in the treatment of diseases, but their effectiveness and specific mechanisms in treating vaginal infections are not clear. Here, we innovatively constructed Escherichia coli Nissle 1917-attB-IFN-α2b (EcN-IFN-α2b) expressing antiviral interferon alpha-2b (IFN-α2b) using genome integration technology, and evaluated its ability to reduce human papillomavirus (HPV) viral load and the underlying mechanisms in an NSG mouse surrogate model of HPV. Our results showed that EcN-IFN-α2b had good growth performance, acid resistance, antioxidant ability, and antimicrobial activity in vitro. EcN-IFN-α2b also significantly reduced the HPV viral load (M vs. EcN-IFN-α2b = 1.003 vs. 0.643, p < 0.01), and effectively alleviated the levels of interleukin 1β (IL-1β) (M vs. EcN-IFN-α2b, p < 0.01), interleukin 6 (IL-6) (M vs. EcN-IFN-α2b, p < 0.01), and tumor necrosis factor α (TNF-α) (M vs. EcN-IFN-α2b, p < 0.05) in the vagina. Further mechanistic studies suggested that EcN-IFN-α2b may reduce HPV viral load by activating the JAK/STAT/cGAS/STING signaling pathway. Additionally, we found that EcN-IFN-α2b altered the composition of vaginal microbiota, especially the relative abundance of vaginal pathogens such as Vibrionaceae_Vibrio, Streptococcus, and Staphylococcaceae_Staphylococcus, and the relative abundance of beneficial Lactobacillus. This study systematically evaluated the effects of the novel engineered strain EcN-IFN-α2b in reducing HPV viral load, alleviating associated inflammation, and restoring vaginal microbiota in an NSG mouse surrogate model, providing a new strategy for the future clinical treatment of HPV infection.

Robot-assisted peritoneal flap vaginoplasty has emerged as an evolving reconstructive option in gender-affirming genital surgery. This systematic review and single-arm meta-analysis aimed to synthesize the available evidence regarding its perioperative, functional canal, and postoperative safety outcomes. This study was conducted according to PRISMA guidelines and prospectively registered in PROSPERO. PubMed, Cochrane Library, Embase, and Web of Science were searched from database inception to May 2026. Eligible studies included transfeminine or gender-diverse individuals undergoing robot-assisted peritoneal flap-based vaginoplasty with extractable clinical outcomes. Continuous outcomes were synthesized as weighted mean estimates with 95% confidence intervals (CIs), and overall postoperative complications were pooled using Stata version 18.0. Heterogeneity was assessed using the I[2] statistic, and leave-one-out sensitivity analyses were performed. Ten studies involving 974 patients were included. The pooled mean operative time was 305.37 min (95% CI 244.62, 366.12), and the pooled length of hospital stay was 5.80 days (95% CI 4.72, 6.87). At the last available follow-up, pooled neovaginal depth was 13.41 cm (95% CI 12.86, 13.96), and pooled neovaginal width was 3.61 cm (95% CI 3.55, 3.67). The pooled overall postoperative complication rate was approximately 30.1%. Sensitivity analyses suggested that the pooled estimates were not driven by any single study. Robot-assisted peritoneal flap vaginoplasty appears feasible and may achieve neovaginal dimensions broadly comparable to those reported for other full-depth vaginoplasty approaches. However, predominantly retrospective single-arm evidence precludes conclusions regarding superiority and highlights the need for standardized prospective studies with longer follow-up and patient-reported outcomes.