Alice Poli

The Relationship Between the Vaginal Microbiota and the Ovarian Cancer Microenvironment: A Journey from Ideas to Insights

Background: The tumor microenvironment offers a new perspective in gynecologic oncology. In ovarian cancer, numerous preclinical studies, especially organoid models, have highlighted cellular, immune, and biochemical mechanisms. Beyond these sophisticated findings, more practical aspects require attention, such as the role of vaginal microbiota, which represents an interplay between external agents and internal genitalia, and its potential profiling role in early detection beyond the promise of microbiota-targeted therapies. Objectives: This review aims to assess whether such a correlation is speculative or scientifically grounded. Methods: A focused literature search was conducted on vaginal microbiota and its correlation with ovarian cancer to define the current state of knowledge. Results: Mixed outcomes have been reported, yet there is a rational and scientific basis supporting further investigation. Clinical approaches increasingly consider vaginal microbiota as relevant. However, we have to say that most available evidence is still preliminary and largely preclinical to set realistic expectations for readers. Although additional studies are needed, emerging insights highlight its importance and practical implications. We present a diagnostic–therapeutic management flowchart summarizing current evidence). Discussion: Most links between the vaginal microbiota and ovarian cancer are correlational rather than causal. The idea that microbes ascend from the vagina to the ovaries is proposed but still definitely not demonstrated. Confounding factors like age, hormones, and BRCA status complicate interpretation, and ovarian cancer itself could secondarily alter the microbiota. Mechanistic studies and longitudinal data are still needed to clarify whether dysbiosis contributes to carcinogenesis or is merely a consequence. As gynecologists, we summarize key aspects and emphasize to colleagues the importance of incorporating these findings into daily clinical practice. Vaginal dysbiosis should be considered not only a local imbalance but also a potential strategy for primary cancer prevention. Conclusions: Future research on the tumor microenvironment and vaginal microbiota will expand scientific knowledge and guide innovative preventive and therapeutic strategies.

Is there a role for the sentinel lymph node in endometrial atypical hyperplasia? Insights from an ESGO-accredited Institution

This study investigates the outcomes of patients with premalignant endometrial findings on biopsy who underwent hysterectomy with sentinel lymph node (SLN) excision and were subsequently diagnosed with endometrial cancer (EC). It aims to highlight the role of nodal assessment in guiding postoperative treatment strategies. Additionally, the study compares surgery complication rates between patients who underwent SLN mapping and those who did not. This retrospective, observational, single-center study was conducted at Udine Hospital between April 2021 and July 2024. 63 patients diagnosed with atypical hyperplasia on endometrial biopsy who underwent hysterectomy and bilateral salpingo-oophorectomy, with or without SLN mapping, were included. All procedures were performed using minimally invasive surgery. Of the 63 patients, 35 (55.6 %) had confirmed atypical hyperplasia on uterine pathology, while 23 (36.5 %) were diagnosed with EC on final pathology. Of the patients who underwent SLN mapping, 18 (43 %) received a final diagnosis of EC and were accurately staged and treated accordingly. In contrast, within the group of patients treated without SLN mapping, 5 (24 %) were diagnosed with EC on final pathology and didn't receive proper staging. No nodal metastases were found in both groups. There was no statistically significant difference in operating time and complication rates between the two groups (with or without SLN mapping), further supporting the procedure's safety. This study's findings underscore the significance of incorporating SLN mapping into hysterectomy and bilateral salpingo-oophorectomy for patients with atypical hyperplasia. This approach enhances accurate staging for patients diagnosed with endometrial cancer on final pathology.

Molecular classification of endometrial carcinoma on endometrial biopsy: an early prognostic value to guide personalized treatment

Molecular features are essential for estimating the risk of recurrence and impacting overall survival in patients with endometrial cancer. Additionally, the surgical procedure itself could be personalized based on the molecular characteristics of the tumor. This study aims to assess the feasibility of obtaining reliable molecular classification status from biopsy specimens collected during hysteroscopy to better modulate the appropriate surgical treatment. This monocentric, retrospective, observational study was conducted on 106 patients who underwent a biopsy procedure followed by radical surgery for endometrial cancer, with concurrent molecular investigation. The molecular classification was determined through immunohistochemical staining for p53 and mismatch repair proteins, along with gene sequencing for POLE. Overall, 106 patients underwent molecular investigation, which was finally achieved on 99 patients (93.4%). Among these, the molecular analysis was conducted in 71 patients (67%) on the pre-operative endometrial biopsy and on the final uterine specimen in 28 patients (26.4%). Most of the endometrial biopsies were performed using Bettocchi hysteroscopy (66%). Molecular analysis was not possible in seven patients (6.6%), with six cases due to sample inadequacy and one case attributed to intra-mucosal carcinoma. The molecular results showed that the copy number low sub-group was the most common, and five cases of 'multiple classifiers' were observed in the low-risk category. Our experience in obtaining molecular information from biopsy samples underscores the feasibility and efficacy of this technique, even in small tissue samples. This capability helps define the prognostic group of patients, facilitates timely decision-making, and develops a personalized strategy for each patient.

The exciting journey of progress: Exploring FIGO 2023 staging for endometrial cancer at a leading ESGO institution

The 2023 FIGO staging of endometrial cancer integrates tumor grade and histology along with molecular features that recognize the prognostic significance of p53 and POLE mutations, accounting for potential conflicts such as lymphovascular space invasion and subserosal invasion. In this single-institution retrospective study, data were collected on 229 endometrial cancer patients from January 2020 to September 2024 and re-stage them according to FIGO 2023 criteria. From FIGO stage 2009 IA, 70 patients do not cross stage (21 are FIGO 2023 IA1 and 49 IA2), 8 patients are upgraded to FIGO IC because of aggressive histotype; 1 is upstaged because of substantial LVSI, and 12 because of aggressive myoinfiltrating tumors (23 % of upstaging). From FIGO 2009 stage IB 34 patients remain in FIGO 2023 IB, while 5 become stage IIB (LVSI) and 27 IIC (aggressive myoinfiltrating), for a total of 32 upstages (48 % of upstaging). Within FIGO 2009 stage II, no proper upstage was possible. We observed a statistical correlation between stages and BMI, as well as between stages and age, for both FIGO 2009 (p = 0.009 and p < 0.001 respectively) and FIGO 2023 (p = 0.002 and p = 0.003 respectively) classifications. Additionally, a correlation was found between tumor grade and BMI (p = 0.02). The FIGO 2023 staging system is gaining importance as recent studies highlight the role of molecular classification in prognosis and personalized therapy. Updating our study's follow-up data will clarify its impact in clinical practice.

Exploring the cost-effectiveness of the OSNA method for patients facing endometrial cancer: Insights from a single-institution experience

The one-step nucleic acid amplification (OSNA) method has emerged as a potential alternative to ultrastaging for diagnosing lymph node metastasis. This study aims to assess the cost-effectiveness of the OSNA technique compared to ultrastaging for detecting SLN metastasis in patients with early-stage endometrial cancer (EC). This retrospective, observational, single-center study included 30 patients with EC who underwent surgical treatment. SLN mapping was performed using an intracervical injection of indocyanine green. SLNs were analyzed and classified as negative, as having isolated tumor cells, micrometastases, or macrometastases. The study evaluated and quantified the costs of the OSNA and ultrastaging procedures in euros. A total of 54 lymph nodes were analyzed using both the OSNA and ultrastaging methods. Concordant negativity was identified in 48 cases (89 %), while micrometastases were detected concordantly in 1 case (1.8 %). The cost for a single ultrastaging lymph node analysis, including immunohistochemistry, is approximately € 250, with a total processing time of 2 days. The cost for a single OSNA analysis is approximately € 236, boasting a significantly shorter processing time of 30-40 min. While materials and staff costs are comparable between both techniques, considering time-related expenses, the OSNA method proves to be more cost-effective than ultrastaging (p < 0.001). The OSNA method demonstrates diagnostic accuracy comparable to histopathological examination in detecting lymph node metastases, reinforcing its reliability for lymph node assessment in patients with EC. Our cost analysis reveals that the OSNA method is more cost-effective than ultrastaging when time-related expenses are considered.