IntroductionImmunosuppressed women with human papillomavirus (HPV)-related genital disease are at increased risk of anal squamous cell carcinoma (ASCC), yet optimal risk stratification and screening strategies remain poorly defined. The aim of this study was to evaluate the prevalence of anal high-grade squamous intraepithelial lesions/anal intraepithelial neoplasia (HSIL/AIN), determine whether the anatomical distribution of genital HPV-associated disease provides clinically relevant information for risk stratification, and to assess the diagnostic performance of different screening strategies in this high-risk population.MethodsA total of 100 immunosuppressed women undergoing ASCC screening were included. All women underwent anal high-risk HPV testing and genotyping and liquid-based cytology, followed by high-resolution anoscopy when indicated.ResultsAnal HPV infection was detected in 77.0% of women, and histologically confirmed HSIL/AIN was detected in 33.0% of the overall cohort. The proportion of women with HSIL/AIN differed according to the anatomical distribution of HPV-related genital lesions. Women with vulvar HSIL, either as isolated disease (52.6%) or as part of multizone HSIL (64.3%), showed the highest proportion of detected HSIL/AIN, whereas HSIL/AIN was detected less frequently among women with HPV infection without genital HSIL (22.2%) (p=0.037 and p=0.007, respectively). Anal HPV testing alone showed high sensitivity (97.0%; 95% CI: 84.2-99.9) and negative predictive value (95.7%; 95% CI: 78.1-99.9), whereas combined strategies slightly increased sensitivity at the expense of lower specificity and higher referral rates.DiscussionIn conclusion, the anatomical distribution of HPV-associated genital disease appears to provide clinically relevant risk stratification. Women with vulvar HSIL represent a priority subgroup for ASCC screening. Anal HPV testing alone showed high sensitivity and NPV. These findings suggest that anal HPV testing may represent a useful primary screening approach in this population.

The incidence of anal squamous cell carcinoma (ASCC) is rising, and women with genital human papillomavirus (HPV) infection or HPV-associated high-grade squamous intraepithelial lesions (HSIL) are at high risk of developing ASCC. We conducted a cross-sectional study including 354 immunocompetent women referred for anal evaluation because of HPV infection or HSIL of the lower genital tract between 2019 and 2024. Participants were categorized according to the genital site affected by HSIL (uterine cervix, vagina, vulva/perineum/perianal region, or multicentric disease), and a control group of 99 immunocompetent women with genital HPV infection and/or low-grade SIL was included. All patients underwent anal high-risk HPV testing, liquid-based cytology, and high-resolution anoscopy when indicated. Overall, high-risk HPV infection and HSIL were identified in the anal canal in 62.5% and 5.6% of women, respectively. Women with multicentric disease showed a higher prevalence of anal HSIL compared with the control group (6/29, 20.7%, vs. 2/99, 2.0%; p = .031), and the other genital HSIL groups (11/182, 6.0% for cervical; 0/13, 0%, for vaginal; 1/31, 3.2% for vulvar HSIL; p = .003). Genital HSIL, particularly multicentric disease, was a strong marker of anal involvement. No HSIL/AIN occurred among women with a negative anal high-risk HPV test. Anal high-risk HPV testing alone showed optimal sensitivity (100%) and negative predictive value (100%) for the diagnosis of HSIL/AIN, whereas cytology alone had lower sensitivity (68.4%). Combining both tests did not improve accuracy and resulted in excessive referrals. High-risk HPV testing alone appears to be the most efficient approach for anal screening in women with genital HSIL.

Cervical cancer is caused by persistent high-risk human papillomavirus (HR-HPV) infection and remains a major global health burden despite available preventive strategies. Most HR-HPV infections and associated low-grade squamous intraepithelial lesions (LSIL) regress spontaneously, yet increasing commercial promotion of topical therapies targeting HPV clearance has emerged in clinical practice. This FIGO/International Gynecologic Cancer Society (IGCS) Position Statement critically appraises the available evidence on topical treatments for HR-HPV infection and LSIL, and provides evidence-based recommendations for clinical practice and future research. No randomized controlled trial has been adequately designed or powered to evaluate the effect of topical therapies on the prevention of histologically confirmed high-grade squamous intraepithelial lesions (HSIL/CIN3+). Available studies are characterized by small sample sizes, short follow-up periods, heterogeneous populations, inadequate comparators, and reliance on surrogate endpoints of uncertain clinical relevance, including cytological regression, HPV nondetection, and immunohistochemical markers such as p16/Ki-67. Published meta-analyses reporting statistically significant improvements in virological and cytological surrogates are limited by substantial heterogeneity, publication bias, and follow-up periods under 1 year. Product-specific appraisal of Coriolus versicolor-based and silicon dioxide/selenite-based vaginal gels reveal additional methodological concerns, including retrospective trial registration, industry funding, and misinterpretation of findings consistent with the spin phenomenon. In the absence of high-quality evidence demonstrating clinically meaningful benefit, FIGO and IGCS do not endorse the routine clinical use of any currently available topical agent for HR-HPV infection or LSIL. Evidence-based surveillance remains the standard of care. Future research should prioritize rigorous trial design with histologically confirmed HSIL/CIN3+ as the primary endpoint, adequate follow-up of at least 3 years, and appropriate comparators. Clinical management should center on informed shared decision-making and evidence-based counseling, rather than on interventions lacking proven clinical benefit.

Sentinel lymph node (SLN) mapping is being explored as a less invasive alternative to systematic lymphadenectomy in early-stage epithelial ovarian cancer. Existing evidence, mainly from feasibility and diagnostic accuracy studies, shows that SLN detection by mapping is achievable, but results remain inconsistent due to heterogeneity in methodology. Detection rates of SLN vary widely across studies, influenced by tracer type, injection technique, timing, and the extent of pathological assessment. Dual-tracer protocols combining radiotracers and indocyanine green generally yield higher detection rates than single tracers do, while injection into both infundibulopelvic and utero-ovarian ligaments yields adequate coverage of para-aortic and pelvic regions. However, detection of pelvic SLNs remains limited. In this context, cervical injection has been proposed as an alternative, with preliminary data showing enhanced pelvic lymph node detection. As for injection timing, pre-adnexectomy injection preserves native lymphatics but is technically demanding; post-adnexectomy injection is technically easier and more widely used. While ultra-staging enhances diagnostic sensitivity, its clinical implications for detecting micro-metastases and isolated tumor cells in epithelial ovarian cancer are still undefined and require further investigation. To support safe and standardized research-based implementation, we propose a unified framework that integrates levels of evidence with grades of recommendation across each procedural domain. This structured approach provides a foundation for protocol development, prospective data collection, and future clinical trials, aiming to bridge the gap between experimental mapping and potential clinical integration in early-stage epithelial ovarian cancer.

Aggressive pelvic angiomyxoma (APA) is a rare, locally infiltrative mesenchymal tumor that primarily affects women of reproductive age. Surgical resection remains the treatment of choice. The high local recurrence rate and insidious growth pattern of APA make preoperative diagnosis crucial for optimal surgical planning. Careful radiological evaluation is vital to determine the full extent of the tumor and to minimize the risk of recurrence. This article presents 3 cases of APA highlighting the radiological characteristics and pathological findings. In all cases, magnetic resonance imaging (MRI) was essential for diagnosis, with typical findings including a hyperintense mass on T2-weighted (T2WI) images with low-signal bands creating a distinctive laminated pattern. This case series emphasizes the importance of recognizing the specific MRI features of APA to guide clinical management and improve patient outcomes.

Sentinel lymph node (SLN) biopsy with ultrastaging is standard in endometrial and vulvar cancers, whereas systematic pelvic lymphadenectomy (PLND) remains recommended in cervical cancer. The SENTIX trial prospectively evaluated the safety of SLN biopsy without PLND in early-stage cervical cancer. Female patients, International Federation of Gynaecology and Obstetrics 2018 stage IA1/LVSI+ to IB2 disease, were enrolled between 2016 and 2020 across 47 sites in 18 countries. All underwent SLN biopsy followed by hysterectomy/trachelectomy. Patients with undetected, unilateral or intraoperatively metastatic SLNs were excluded from the intention-to-treat cohort. SLNs were assessed by pathological ultrastaging. Of 731 patients enrolled, 594 formed the intention-to-treat cohort. SLN metastases were identified in 82 patients (12%), 56.1% intraoperatively and 43.9% by ultrastaging. At 2 years, the recurrence rate was 6.1% (one-sided 95% CI 7.9%), confirming noninferiority to the 7% reference rate. Two-year disease-free and overall survival rates were 93.3% (95% CI 94.9-91.6) and 97.9% (95% CI 98.9-97.0), respectively. Here we show that SLN biopsy without systematic PLND did not increase the risk of recurrence in patients with early-stage cervical cancer. Pathological ultrastaging of SLNs detected about 44% of N1 cases, which would be missed by a standard lymph node assessment. Trial registration: ClinicalTrials.gov ( NCT02494063 ).

OBJECTIVE:Lymph node (LN) metastasis is a key prognostic factor in locally advanced cervical cancer (LACC), especially at the aortic level. Prophylactic extended-field radiotherapy (EFRT) indications are being evaluated, as imaging (r) may miss low-volume aortic LN disease in patients with pelvic LN metastasis. Our aim was to describe the distribution of pelvic and aortic LN metastasis confirmed by histology in patients with FIGO stage IIIC1r LACC. METHODS:This multicenter retrospective study included women with FIGO stage IIIC1r LACC treated with chemoradiotherapy and pretherapeutic nodal surgical staging with laparoscopic extraperitoneal aortic lymphadenectomy to the left renal vein and debulking of pathological pelvic LN on imaging. Imaging for stage IIIC1r diagnosis included MRI and/or PET-scan. LN metastasis distribution was categorized by location: pelvic or aortic and supra- or inframesenteric. RESULTS:We included 164 patients, 96.3 % evaluated with MRI and 35 % with PET-scan. The median number of excised LN was 12 aortic and 8.5 pelvic. Pelvic LN metastasis was confirmed in 73 patients (44.5 %), of whom 31 (42.5 %) had aortic LN metastasis: 24.7 % inframesenteric, 4.1 % supramesenteric, and 13.7 % both. Pelvic LN were negative in 96 patients (58.5 %), of whom 11 (11.5 %) had aortic LN metastasis: 7.3 % inframesenteric, 3.1 % supramesenteric, and 1 % both. CONCLUSIONS:In stage IIIC1r LACC, pelvic LN metastasis are confirmed in less than 50 % of patients following surgical evaluation. The risk of aortic LN involvement is higher when there are metastases at the pelvic level but not exclusively. The rate of supramesenteric disease supports extending the EFRT to the left renal vein.

OBJECTIVE:Prehabilitation, defined as the preparatory intervention to increase patient preparedness in the lead-up to surgery, has shown a decrease in post-operative complications in various types of surgery. However, there is limited evidence in advanced ovarian cancer surgery. This study aimed to evaluate the benefits of multimodal prehabilitation in advanced ovarian cancer patients in terms of improving physical functioning, body composition, and psychological well-being during the pre-operative period. METHODS:This single-center, ambispective study included patients with advanced ovarian cancer eligible for primary or interval cytoreductive surgery. Participants attended a multimodal prehabilitation program comprising medical optimization, supervised exercise training, nutritional counseling and supplementation, and psychological support. Functional capacity, nutritional status, and psychological well-being were assessed before the start of the program and before surgery. RESULTS:62 patients were referred for the multimodal prehabilitation program from July 2019 to May 2023. Median adherence to the training program reached 75% (IQR 58-87%). 35 patients (59%) were evaluated pre-operatively. Patients attended a median of 8 (IQR 6-12) supervised exercise training sessions with no differences between those who underwent primary or interval cytoreductive surgery (p=0.80). A significant improvement was observed in functional capacity according to the 6 min walk test (mean 33.1 m, 95% CI 10.5 to 55.5) as well as in the 30 s sit-to-stand test (+3.3 repetitions, 95% CI 1.8 to 4.8), with both being above the minimal clinically important difference of 14 m and two repetitions, respectively. Patients also reported a significant decrease in depression, anxiety, and total scores of the Hospital Anxiety and Depression Scale. CONCLUSIONS:Multimodal prehabilitation in patients with advanced ovarian cancer undergoing cytoreductive surgery improves pre-operative physical functioning and decreases emotional distress. Further controlled studies with a larger sample size are warranted to corroborate improvement in functional capacity, body composition, and psychological well-being through prehabilitation programs.

To evaluate the oncologic and survival outcomes in patients diagnosed with early-stage cervical cancer who underwent both sentinel lymph node (SLN) and pelvic lymphadenectomy (PLD) compared with those who underwent SLN alone at primary surgery. From 2001 to 2022, women who underwent SLN biopsy for nodal staging were recruited. The group of women who underwent SLN biopsy and PLD (SLN + PLD group) was compared with the group who underwent SLN mapping alone (SLN group). 210 patients were evaluated (98 and 112 in each group). The overall SLN detection rate was 97.6

BACKGROUND:Patients with cervical cancer treatment experience an impairment of sexual function and quality of life. This issue is usually underreported and undertreated, and evidence-based interventions are lacking. Prevention of sexual dysfunction is a crucial pillar in improving the quality of life of these patients. The primary objective of this trial is to evaluate the impact of a multimodal intervention, encompassing prevention of vaginal dysfunction and patient education, on sexual function and quality of life in cervical cancer survivors utilizing patient-reported outcome measurements. METHODS:Multi-institutional, randomized clinical trial where patients will be randomized 1:2 at diagnosis of initial or locally advanced cervical cancer to control arm or intervention arm. After treatment, control arm patients will undergo standard follow-up by their referring physician. The multimodal intervention for patients in the intervention group includes application of vaginal estrogens plus hyaluronic-acid cream along with use of vaginal vibrator, systematic evaluation of the need of systemic hormone replacement therapy and treatment if needed, and access to online content about sexuality, nutrition, sports and lifestyle habits. Through 4 appointments (at diagnosis, 1, 6, and 12 months after treatment), sexual health, vaginal trophism and self-perceived quality of life of patients in both arms will be assessed with validated questionnaires as female sexual function index (FSFI), European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30, and Cx-24, Cervantes Scale, vaginal health index and vaginal thickness assessed by ultrasound. The major inclusion criteria will be patients aged ≥18 years with the International Federation of Gynecology and Obstetrics stage I-III cervical cancer treated with surgery and/or radiotherapy. The primary endpoint will be FSFI score 12 months after treatment, which will be compared between groups. Uni- and multivariate analysis will be performed to identify factors influencing sexual function recovery after treatment. The sample size will be of 120 eligible patients, who will be randomized to detect an improvement of 5.2 points in FSFI score. Complete accrual is estimated in March 2026. To date, the present study has no external funding. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT06031493.

To evaluate the detection rate of sentinel lymph node (SLN) mapping in early-stage ovarian cancer using [99mTc]Tc-nanocolloid and indocyanine green (ICG), and the added value of an intraoperative gamma camera. This was a prospective single-center trial of 63 patients with suspected early-stage epithelial ovarian cancer who underwent SLN mapping with combined tracers. [99mTc]Tc-nanocolloid was injected into the ovarian ligaments before adnexectomy, and if malignancy was confirmed on intraoperative frozen section, ICG was administered after adnexectomy in immediate staging cases. SLNs were identified using a handheld gamma probe, the gold standard, and a portable gamma camera for radiotracer localization, alongside near-infrared imaging for ICG. We calculated SLN detection rates for each tracer and concordance between the tracers (reflecting the impact of injection timing), including identification of the same SLN— as well as between detection modalities. Cohen’s κ and PABAK were used to assess concordance between detection modalities. Patients with confirmed malignancy underwent complete pelvic and aortic lymphadenectomy. Among 63 patients, sentinel lymph nodes (SLNs) were detected in 79.4

Transcriptomics generates promising data for personalized medicine, but its clinical utility is hindered by technical barriers associated with formalin-fixed, paraffin-embedded samples. Advances in automation and simplified workflows are key for integrating these technologies into routine care. We have developed HTGAnalyzer, an R package that enables bulk transcriptomics analysis from multiple data sources, such as HTG EdgeSeq and RNA-seq. Designed with clinical and molecular diagnostics in mind, HTGAnalyzer includes a fully automatic pipeline that performs sample quality control, data normalization, and a set of transcriptomic and clinical analyses. Importantly, HTGAnalyzer provides quality control and analysis tailored for HTG data, filling the gap left by HTG closure with no alternative solutions. Designed for ease of use without knowledge of bioinformatics, it features a user-friendly Shiny app, standardized functions for easy Docker setup, and enhanced connectivity to clinical data management systems. It delivers a complete analytical workflow in less than 20 min on a standard PC (Intel i7-7500U, 16 GB RAM). We applied HTGAnalyzer to diverse datasets, including a new vulvar cancer cohort, and generated interpretable reports with rich visual outputs. In summary, HTGAnalyzer offers robust quality control and advanced analytics in a single, unified tool, supporting the clinical use of transcriptomics in precision medicine.