Introduction Endometriosis is characterized by the ectopic implantation of endometrial tissue affecting reproductive-aged women. Available therapies have still unmet needs namely due to recurrence rates and systemic side effects. Emerging evidence suggests endometrial stem cells (EnSCs) contribution in disease pathogenesis, including mesenchymal stem cells (E-MSCs), epithelial progenitor cells (EPCs), and side population cells (ESPs). These stem/progenitor cells are involved in proliferation, migration, and angiogenesis, contributing to endometriosis genesis and persistence. Targeting EnSCs and their regulatory pathways present a promising therapeutic strategy to improve unmet needs in endometriosis. Materials and Methods This scoping review was based on a systematic literature search conducted in PubMed, EMBASE, and Web of Science considering studies published after 2000. Inclusion criteria focused on original research articles exploring the role and targeting of EnSCs in endometriosis, following PRISMA-ScR guidelines. Data were synthesized through narrative and descriptive methods. Results The review structures key pathways and therapeutic agents targeting EnSCs in endometriosis. Notch1, PI3K/Akt, Wnt/β-catenin, and JAK/STAT signalling are pathways that regulate proliferation, migration and survival of EnSCs in endometriosis. Agents such as metformin, lovastatin, sorafenib, quinagolide, and γ-secretase inhibitors demonstrated potential to modulate stemness, leading to a decrease in inflammation, migration and apoptosis. Anti-angiogenic agents showed efficacy in reducing lesion size in vivo, targeting E-MSCs. Exosomes emerge as a cell-free approach, derived from menstrual stem cells (MenSCs) or ginger-based nanoparticles and exhibited properties essential for endometriosis treatment, directed to ectopic stem cells. Conclusions EnSCs sustain aberrant cellular behaviours in endometriosis. Targeting EnSCs and their related pathways may be an innovative, individualized, and disease-modifying strategy. Pharmacological modulation, gene therapy and exosome are strategies for stem cell inhibition in endometriosis, being a promising avenue for future research leading to application in clinical practice.

Novel blood biomarkers are crucial for HPV-related cancers to overcome the limitations of imaging and biopsies. This review evaluates the diagnostic performance of circulating cell-free DNA (cfDNA) fragmentomic patterns, distinguishing host-genome integrity from specific viral signatures. Following PRISMA guidelines, we searched PubMed, EMBASE, and Web of Science up to February 2026. Methodological quality was assessed via QUADAS-2, and diagnostic performance was synthesized using a random-effects model. From 489 records, six studies (215 patients, 209 controls) met inclusion criteria. Lacking host-derived fragmentomics data, the analysis focused exclusively on the structural size profiles of circulating viral DNA (cfHPV-DNA). Meta-analysis of four cohorts specifically evaluating these viral fragmentation patterns yielded a pooled Diagnostic Odds Ratio (DOR) of 205.73 (95% CI: 44.72-946.38). Specificity was robust (~100%), with high sensitivity (>90%) for macroscopic disease. However, sensitivity decreased in low-tumor-burden cohorts. cfHPV-DNA fragmentation patterns shows promising diagnostic potential for macroscopic HPV-driven malignancies. However, further studies must determine whether fragment sizing truly outperforms binary viral detection and correlates with disease severity. Furthermore, while current assays exploit the analytical simplicity of viral targets, host-derived fragmentomics remains an overlooked compartment that warrants exploration to determine its true clinical value regarding underlying tumor dynamics. Systematic Review Registration: PROSPERO, identifier: CRD420251052768.

Background/Objectives: Cervical cancer remains a significant global health burden, underscoring the imperative for refined diagnostic and prognostic methodologies. This study aimed to evaluate the potential of extracellular vesicles (EVs) as non-invasive biomarkers for cervical cancer, focusing on diagnosis and prognosis. Methods: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines to assess the diagnostic and prognostic accuracy of EV-based biomarkers. We searched PubMed, EMBASE, and Web of Science for relevant studies. Twelve articles met the inclusion criteria: eight related to diagnostic accuracy, three to prognosis, and one to both outcomes. Six studies met the criteria for meta-analysis. We used a random-effects model to synthesise diagnostic data, while prognostic data were synthesised narratively. Results: The meta-analysis yielded a pooled area under the receiver operating characteristic curve (AUC) of 0.87 (95% CI 0.80–0.92) for EVs in the diagnosis of cervical cancer, indicating high accuracy. The evaluated diagnostic biomarkers were primarily non-coding RNAs. For prognosis, data heterogeneity precluded quantitative synthesis; however, individual studies identified diverse EV-associated molecules correlated with recurrence and survival. GRADE assessment indicated a high risk of bias and heterogeneity across studies. Conclusions: Extracellular vesicles demonstrate robust promise as diagnostic biomarkers for cervical cancer; however, their prognostic utility remains inconclusive due to methodological and clinical heterogeneity. Future research must prioritise the standardisation of isolation protocols and the execution of large-scale, prospective studies to validate EV biomarkers for clinical application. Systematic Review Registration: PROSPERO, identifier: CRD420251014411.

Ovarian cancer is the most lethal gynaecologic malignancy, with high-grade serous ovarian carcinoma representing the most prevalent and aggressive subtype. Despite advances in surgery and chemotherapy, recurrence remains high, highlighting the need for novel therapeutic approaches. Progesterone plays a dual role in ovarian cancer, acting both as a potential tumour suppressor and, in specific genetic contexts, as a carcinogenic factor. While hormone therapy remains underutilized, emerging evidence supports its relevance in selected patient populations. This narrative review aims to explore the physiological and pathological roles of progesterone in ovarian cancer and its potential as a therapeutic target, to identify future research opportunities, focused on molecular stratification to optimize endocrine strategies and integrate hormonal biomarkers into clinical decision-making.

Circulating tumour DNA (ctDNA) facilitates longitudinal study of the tumour genome, which, unlike tumour tissue biopsies, globally reflects intratumor and intermetastatis heterogeneity. Despite its costs, next-generation sequencing (NGS) has revolutionised the study of ctDNA, ensuring a more comprehensive and multimodal approach, increasing data collection, and introducing new variables that can be correlated with clinical outcomes. Current NGS strategies can comprise a tumour-informed set of genes or the entire genome and detect a tumour fraction as low as 10−5. Despite some conflicting studies, there is evidence that ctDNA levels can predict the worse outcomes of ovarian cancer (OC) in both early and advanced disease. Changes in those levels can also be informative regarding treatment efficacy and tumour recurrence, capable of outperforming CA-125, currently the only universally utilised plasma biomarker in high-grade serous OC (HGSOC). Qualitative evaluation of sequencing shows that increasing copy number alterations and gene variants during treatment may correlate with a worse prognosis in HGSOC. However, following tumour clonality and emerging variants during treatment poses a more unique opportunity to define treatment response, select patients based on their emerging resistance mechanisms, like BRCA secondary mutations, and discover potential targetable variants. Sequencing of tumour biopsies and ctDNA is not always concordant, likely as a result of clonal heterogeneity, which is better captured in the plasma samples than it is in a large number of biopsies. These incoherences may reflect tumour clonality and reveal the acquired alterations that cause treatment resistance. Cell-free DNA methylation profiles can be used to distinguish OC from healthy individuals, and NGS methylation panels have been shown to have excellent diagnostic capabilities. Also, methylation signatures showed promise in explaining treatment responses, including BRCA dysfunction. ctDNA is evolving as a promising new biomarker to track tumour evolution and clonality through the treatment of early and advanced ovarian cancer, with potential applicability in prognostic prediction and treatment selection. While its role in HGSOC paves the way to clinical applicability, its potential interest in other histological subtypes of OC remains unknown.

Gonadotoxicity resulting from systemic and locoregional cancer treatments significantly threatens women’s reproductive health, often culminating in premature ovarian insufficiency. These therapies, particularly alkylating agents and ionizing radiation, induce DNA damage and apoptosis in ovarian follicles, leading to infertility, amenorrhea, and estrogen deficiency, which exacerbate risks of osteoporosis and cardiovascular diseases. Existing fertility preservation methods do not prevent immediate ovarian damage, underscoring the need for innovative protective strategies. Menstrual blood-derived stem cells (MenSC) and their extracellular vesicles (EV) present promising regenerative potential due to their therapeutic cargo delivery and pathway modulation capabilities. Preclinical studies demonstrate that MenSC-derived EV ameliorate premature ovarian insufficiency by inhibiting granulosa cell apoptosis, promoting angiogenesis, and activating pivotal pathways such as SMAD3/AKT/MDM2/P53. However, comprehensive research is imperative to ensure the safety, efficacy, and long-term effects of MenSC-derived EV in clinical practice. In this review, we update the current knowledge and research regarding the use of MenSC-derived EV as a novel therapeutic weapon for ovarian regeneration in the context of gonadotoxicity induced by systemic anticancer treatment.

In the management of early-stage breast cancer (BC), lymph nodes (LNs) are typically characterised using the One-Step Nucleic Acid Amplification (OSNA) assay, a standard procedure for assessing subclinical metastasis in sentinel LNs (SLNs). The pivotal role of LNs in coordinating the immune response against BC is often overlooked. Our aim was to improve prognostic information provided by the OSNA assay and explore immune-related gene signatures in SLNs. The expression of an immune gene panel was analysed in SLNs from 32 patients with Luminal A early-stage BC (cT1-T2 N0). Using an unsupervised approach based on these expression values, this study identified two clusters, regardless of the SLN invasion: one evidencing an adaptive anti-tumoral immune response, characterised by an increase in naive B cells, follicular T helper cells, and activated NK cells; and another with a more undifferentiated response, with an increase in the activated-to-resting dendritic cells (DCs) ratio. Through a protein—protein interaction (PPI) network, we identified seven immunoregulatory hub genes: CD80, CD40, TNF, FCGR3A, CD163, FCGR3B, and CCR2. This study shows that, in Luminal A early-stage BC, SLNs gene expression studies enable the identification of distinct immune profiles that may influence prognosis stratification and highlight key genes that could serve as potential targets for immunotherapy.

Establishing an accurate prognosis for women diagnosed with breast cancer (BC) is extremely challenging. Axillary lymph node (ALN) evaluation is considered of major prognostic value. The one-step nucleic acid amplification (OSNA) assay is currently used for assessing axillary sentinel lymph node (SLN) status in BC. Additionally, total tumor load (TTL) may help predict further metastatic axillary involvement beyond the SLN. The prognostic value of primary BC location remains controversial due to lack of consensus on the biological differences among tumors at various sites. Evidence suggests that tumors in the internal quadrants (INLs) have worse prognosis compared to those in the external quadrants. Furthermore, ALN involvement is believed to be mainly associated with external quadrant tumors, mainly due to the lymphatic drainage system of the breast. This pilot observational study, despite lacking a control group and having a relatively small sample size, is the first to evaluate the potential relationship between primary BC location and ALN metastasis using the OSNA assay. A sample of consecutive BC patients undergoing axillary staging with the OSNA assay were included. Tumors were categorized into three groups based on primary location: external quadrants and axillary tail (EXL), INLs, and nipple and areola location (NAL). Although not statistically significant, the INL group exhibited a higher mean TTL. Additionally, no significant differences were observed between groups concerning SLN detection techniques, SLN status, number of metastatic SLN, or mean TTL. These findings support the use of the innovative tracer superparamagnetic iron oxide regardless of tumor site. This study underscores the importance of understanding the relationship between BC location and ALN status, which may improve prognostic stratification and targeted therapies based on tumor site. If these observations are confirmed in larger, multicentric studies, the potential conclusions may shift the paradigm of INL tumor treatment, significantly impacting clinical practice and research.

Risk-reducing bilateral salpingo-oophorectomy (RRSO) is recommended for breast cancer gene 1 (BRCA1) and 2 (BRCA2) mutation carriers. A major consequence of RRSO is surgical menopause associated with severe menopausal symptoms, mostly genitourinary complaints. Due to the inherent breast cancer risk, estrogen-based therapies are generally avoided in these patients. So far, the non-hormonal approaches available are not efficient to successfully treat the disabling vaginal atrophy-related symptoms. In regenerative medicine, mesenchymal stem cells (MSC) are the most frequently used cell type due to their remarkable and regenerative characteristics. Therapies based on MSC have revealed positive outcomes regarding symptoms and signs associated with vaginal atrophy by promoting angiogenesis, vaginal restoration, and the proliferation of vaginal mucosa cells. Menstrual blood-derived stem cells (MenSC) are a novel source of MSC, with promising therapeutic potential directly linked to their high proliferative rates; low immunogenicity; non-invasive, easy, and periodic acquisition; and almost no associated ethical issues. In this review, we update the current knowledge and research regarding the potential value of previously preserved MenSC in the therapy of vaginal atrophy among BRCA mutation carriers subjected to RRSO.

Objective: Abdominal wall endometriosis (AWE) is a rare form of extragenital endometriosis that usually develops in association with a prior surgical scar. The purpose of the study was to review the clinical characteristics, diagnostic methods, treatment modalities, and outcomes of patients with AWE. Methods: A descriptive cross-sectional study was performed in a Gynecology Department of a Portuguese tertiary hospital, concerning patients with histologic-proven AWE, between January 2012 and December 2020 (n = 22). Statistical analysis was performed using IBM SPSS Statistics Version 27.00, with a significance level of p < 0.05. Results: The most common locations of extrapelvic endometrial ectopic implants were cesarean delivery scar (n = 13, 59.1%) and the umbilicus (n = 5, 22.7%). The median (range) age was 36 (30-42) years old, and all patients had a history of previous surgery but one. Nineteen patients had undergone a previous cesarean section, and the mean (range) time from surgery to the onset of symptoms was 100 (32-168) months. All patients were symptomatic and presented with a palpable mass at physical examination. The majority complained of a painful abdominal mass (n = 20, 90.9%) which was associated with cyclic pain in thirteen patients (65%). Ultrasound scan was performed in all patients and the nodules had a median size of 20.5 mm (5-93 mm). One patient received hormonal therapy and surgical resection was performed in the remaining patients. The nodule’s median (range) size was 31 (12-50) mm on gross examination. Conclusion: AWE should be considered in the presence of a previous pelvic surgery history associated with abdominal scar cyclic pain and swelling. A careful history and clinical examination are essential for diagnosis to avoid unnecessary delay before surgical intervention.

Inflammatory myofibroblastic tumor (IMT) is a rare entity and its occurrence in breast is very uncommon. Only a few clinical cases have been reported in literature. World Health Organization consider IMT a borderline lesion due to its tendency to recur locally and because of a small risk of malignant transformation and metastization. The aim of the study was to analyse myofibroblastic inflammatory breast tumors diagnosed in the last fifteen years. Four patients were diagnosed with IMT, one of them bilateral. Three cases were suspected on screening mammography and the remaining tumor was detected as a palpable mass during a routine breast examination. Core needle biopsy was performed in all patients, but histology was not conclusive in anyone, and surgical excision was decided. A complete tumoral excision with negative margins was performed in three patients, and in the remaining patient a positive surgical margin was observed with bilateral relapse, pointing out the importance of complete excision with clear margins. Although in majority of cases it presents a benign course, close follow-up is important to detect early recurrence or malignant transformation. More studies are needed to find out predictive markers for high recurrence rate and malignant transformation to do a close follow-up and prevent breast malignancies.

The development of new technologies such as sequencing has greatly enhanced our understanding of the human microbiome. The interactions between the human microbiome and the development of several diseases have been the subject of recent research. In-depth knowledge about the vaginal microbiome (VMB) has shown that dysbiosis is closely related to the development of gynecologic and obstetric disorders. To date, the progress in treating or modulating the VMB has lagged far behind research efforts. Photobiomodulation (PBM) uses low levels of light, usually red or near-infrared, to treat a diversity of conditions. Several studies have demonstrated that PBM can control the microbiome and improve the activity of the immune system. In recent years, increasing attention has been paid to the microbiome, mostly to the gut microbiome and its connections with many diseases, such as metabolic disorders, obesity, cardiovascular disorders, autoimmunity, and neurological disorders. The applicability of PBM therapeutics to treat gut dysbiosis has been studied, with promising results. The possible cellular and molecular effects of PBM on the vaginal microbiome constitute a theoretical and promising field that is starting to take its first steps. In this review, we will discuss the potential mechanisms and effects of photobiomodulation in the VMB.

BACKGROUND:Human papillomavirus (HPV) infection is one of the most prevalent sexually transmitted infections that can lead to malignant pathologies as well as fertility problems. The aim of this study was to evaluate the prevalence of HPV infection in males, its impact on semen parameters, and reproductive consequences. We also evaluated potential measures that could prevent negative outcomes of HPV infection in males. METHODS:A systematic literature search using PubMed/Medline and Embase databases was performed to search for English articles published until July 2023. We explored three different aspects: (1) prevalence of HPV semen infection and its impact on seminal parameters; (2) the relationship between HPV semen infection and infertility risk and reproductive outcomes; and (3) potential measures that could prevent the negative outcomes related to HPV seminal infection. The identified studies were first screened and assessed independently by one author, and then validated by two additional authors. Data were extracted from 19 studies. RESULTS:The prevalence of seminal HPV infection was higher among infertile males. In addition to controversies about the real interference of seminal HPV infection on sperm parameters, a growing number of studies have demonstrated a correlation between unexplained infertility and seminal HPV infection. Semen HPV infection is also associated with lower rates of pregnancy and higher rates of miscarriage. Prevention measures such as HPV vaccination seem promising. CONCLUSION:Further studies are required to confirm not only the association between HPV infection and reproductive outcomes but also the benefit of preventive measures.

Risk-reducing bilateral salpingo-oophorectomy (RRSO) is an effective prophylactic surgery provided to premenopausal women carrying BRCA1 or BRCA2 mutations and presenting an increased risk of developing breast or ovarian cancer. This procedure is related to physiological, sexual, and psychosocial distress, which altogether increase uncertainty and complexity in the clinical decision-making process and post-surgery adaptation. Physician-patient communication (PPC) has been pointed out as a determinant factor in the decision-making to undergo RRSO, and the subsequent adjustment of women. However, studies examining the psychosocial impact of the decision-making process have been scarce and often lack clear theoretical frameworks. While the role of PPC in such processes has been highlighted in a few qualitative studies, there is a paucity of quantitative research addressing this question. Therefore, this narrative review, conducted using a multidisciplinary approach, was planned to: (1) present an updated medical background for RRSO; (2) analyze the psychosocial impact of the decision-making process within a theoretical framework of the Health Belief Model; and (3) discuss the role of PPC in such a decision-making process and in post-surgery. The collected research also enabled the recommendation of some additions to the existing clinical guidelines and the outlining of future research directions.

Invasive breast cancer with axillary lymph node (LN) invasion is a continuing problem worldwide. The morbidity associated with axillary LN dissection along with the high rate of nodal downstaging after neoadjuvant chemotherapy (NACT) made the standard treatment shift towards less invasive surgery. Sentinel lymph node biopsy (SLNB) after NACT is associated with high false-negative rates (13%-14%). To overcome this problem, it was concluded that the positive nodes should first be indicated with image-detectable markers and then removed together with SLNB: targeted axillary dissection (TAD). This review aims to describe and evaluate the different marking techniques for TAD in patients with node-positive breast cancer treated with NACT, namely: clip placement and guidewire localization; clip placement and 125I-labelled radioactive seed localization; clip placement and skin mark; clip placement and intraoperative ultrasound; tattooing with a sterile black carbon suspension; magnetic seeds; radar and infrared light technology localization. Targeted axillary dissection techniques have shown false-negative rates below 9% and identification rates above 95%. The most studied technique is guidewire localization, as it is also the oldest one. However, according to data gathered from this review, some newer techniques have shown to be very promising due to their statistical results and management factors.

The human endometrium has a complex cellular composition that is capable of promoting cyclic regeneration, where endometrial stem cells play a critical role. Menstrual blood-derived stem cells (MenSC) were first discovered in 2007 and described as exhibiting mesenchymal stem cell properties, setting them in the spotlight for endometriosis research. The stem cell theory for endometriosis pathogenesis, supported by the consensual mechanism of retrograde menstruation, highlights the recognized importance that MenSC have gained by potentially being directly related to the genesis, development and maintenance of ectopic endometriotic lesions. Meanwhile, the differences observed between MenSC in patients with endometriosis and in healthy women underlines the applicability of these cells as a putative biomarker for the early diagnosis of endometriosis, as well as for the development of targeted therapies. It is expected that in the near future MenSC will have the potential to change the way we manage this complex disease, once their long-term safety and effectiveness are assessed.

Ductal carcinoma in situ (DCIS) is a putative precursor of invasive breast cancer and MRI is considered the most sensitive imaging technique for its detection. This study aims to evaluate the accuracy of MRI measuring the pure DCIS size, against pathology, to better understand the role of MRI in the management of this intraductal neoplasm.Potentially eligible studies in MEDLINE, Embase and Google Scholar, up to January 2021 were considered, and a systematic review and meta-analysis according to the published protocol (Prospero-CRD42021232228) was performed. Outcomes of mean differences and accuracy rates were analysed using IBM® SPSS® v26 and random-effect models in platform R v3.3.Twenty-two cross-sectional studies were selected and 15 proceeded to meta-analysis. MRI accurately predicted 55% of the tumours’ sizes and, according to Bland–Altman plots, concordance between MRI and pathology was greater for smaller tumours. In the meta-analysis, difference of the means between MRI and pathology was 3.85 mm (CI 95% [−0.92;8.60]) with considerable heterogeneity (I2 = 96.7%). Subgroup analysis showed similar results for sizes between different MRI fields, temporal resolution, slice thickness and acquisition times, but lower heterogeneity in studies using 3-T MRI (I2 = 57.2%). Results were concordant with low risk of bias studies (2.46, CI 95% [0.57–4.36]), without heterogeneity (I2 = 0%).Therefore, MRI is shown to be an accurate method in pure DCIS size assessment. Once the best MRI protocol is established, evaluation of the impact of pure DCIS size in predicting treatment outcomes will contribute to clarifying current issues related to intraductal breast carcinoma.

The One Step Nucleic Acid Amplification (OSNA) is being adopted worldwide for sentinel lymph nodes (SLNs) staging in breast cancer (BC). As major disadvantage, OSNA precludes prognostic information based on structural evaluation of SLNs. Our aim is to identify biomarkers related to tumor-microenvironment interplay exploring gene expression data from the OSNA remaining lysate. This study included 32 patients with early stage hormone receptors-positive BC. Remaining OSNA lysates were prepared for targeted RNA-sequencing analysis. Identification of differentially expressed genes (DEGs) was performed by DESeq2 in R and data analysis in STATA. The results show that, in metastatic SLNs, several genes were upregulated: KRT7, VTCN1, CD44, GATA3, ALOX15B, RORC, NECTIN2, LRG1, CD276, FOXM1 and IGF1R. Hierarchical clustering analysis revealed three different clusters. The identified DEGs codify proteins mainly involved in cancer aggressiveness and with impact in immune response. The overexpression of the immune suppressive genes VTCN1 and CD276 may explain that no direct evidence of activation of immune response in metastatic SLNs was found. We show that OSNA results may be improved incorporating microenvironment-related biomarkers that may be useful in the future for prognosis stratification and immunotherapy selection. As OSNA assay is being implemented for SLNs staging in other cancers, this approach could also have a wider utility.

Background: The one-step nucleic acid amplification (OSNA) assay quantifies the cytokeratin 19 (CK19) messenger RNA copy number, which is currently being used for assessment of axillary sentinel lymph node (SLN) status in breast cancer. The total tumour load (TTL), defined as the total amount of CK19 mRNA copies in all positive SLNs, may help predicting additional metastatic axillary involvement besides SLN. There is evidence suggesting that palpable and non-palpable breast tumours manifest distinct pathological features, making tumour palpability a putative predictive factor of axillary lymph node involvement. This is the first study aiming to evaluate the potential relationship between breast tumour palpability and SLN biopsy with OSNA assay.