Disclosure: N. Angelopoulos: None. D.G. Goulis: None. S. Livadas: None. R. Paparodis: None. I. Androulakis: None. A. Boniakos: None. J.C. Jaume: None. I. Iakovou: None.Purpose. Ultrasonography (US) is the most accurate and cost-effective imaging method for identifying thyroid nodules. The difficulty in determining which nodules to sample for fine-needle aspiration (FNA) cytology has prompted the introduction of the Thyroid Imaging Reporting and Data Systems (TIRADS), which assesses the malignancy risk associated with thyroid nodules. Real-time elastography (RTE), coupled with strain ratio (SR) measurements, offers a means to evaluate the nodule stiffness and potentially discern their likelihood of being malignant. The present study aimed to investigate the efficacy of RTE and SR, combined with the TIRADS grading systems, in distinguishing between benign and malignant thyroid nodules. Methods. From 1094 patients with thyroid nodules referred for thyroid ultrasound at a University Hospital, those with thyroid nodules ≥20 mm in diameter were enrolled. Each nodule was categorized according to European (EU)- and American College of Radiology (ACR)-TIRADS systems, ranging from 2 to 5. Nodules’ semiquantitative SRs were evaluated together with RTE. The thyroid nodule diagnosis was documented by post-thyroidectomy histopathological examination and/or US-guided FNA according to the Bethesda classification of the examined smears.Results. The study involved 267 patients (mean age 60.3 ± 14.3 years; 46 males and 221 females) with 308 nodules categorized into EU-TIRADS categories 3, 4, and 5. Of these nodules, 22 proved malignant, and 286 benign. The elastography ratio exhibited high predictive performance in diagnosing thyroid malignancy (p<0.001) at a threshold value of >0.84 (sensitivity 90.9%, specificity 73.4%). In the 168 nodules with EU-TIRADS 3, this threshold had 100% sensitivity and 75.1% specificity in discriminating malignant thyroid nodules.Conclusion. Combining TIRADS with data derived from RTE reduces unnecessary FNAs and surgeries in patients with thyroid nodular disease.Presentation: Sunday, July 13, 2025

Disclosure: S. Uysal: None. C. Sulu: None. B.B. Kocaman: None. I. Muradov: None. L. Soltanova: None. S. Sahin: None. H.M. Ozkaya: None. D. Konukoglu: None. T. Damci: None. M.S. Gonen: None.Background: To investigate the relationship between thyroglobulin (Tg) levels obtained from thyroid fine-needle aspiration (FNA) and cytopathological results.Methods: This cross-sectional study included patients who underwent FNA between January 2023 and August 2024 in accordance with the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) risk scoring. Patients with pure cystic nodules, non-thyroid malignancy, and major psychiatric disorders that could interfere with compliance during the procedure were excluded from the study. FNA-Tg samples were obtained from the nodules using a 22-gauge needle on the first attempt. FNA-Tg levels were then measured by electrochemiluminescence immunoassay. These levels were compared among different patient groups, classified according to the cytopathological examination results based on the Bethesda System for Reporting Thyroid Cytopathology. Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 20.Results: The study included 193 FNA samples in 193 patients. In 148 (76.7%) out of 193 samples the aspirate was diagnostic. Of these, 101 (68.2%) were benign (Bethesda II), 29 (19.6%) were indeterminate (Bethesda III-IV), and 18 (12.2%) were malignant (Bethesda V-VI). FNA-Tg levels were significantly higher in benign nodules compared to malignant ones (p<0.001). There was no significant difference between concomitant serum Tg levels in patients with benign and malignant nodules (p=0.614). An FNA-Tg value above 13262 ng/ml predicted benign cytology with 71.3% sensitivity and 77.8% specificity. Conclusions: FNA-Tg levels may provide valuable insights into FNA cytology and serve as an effective marker for distinguishing benign nodules from those with malignant characteristics.Presentation: Monday, July 14, 2025

SMARCA4-deficient cervical adenocarcinoma is an exceedingly rare and aggressive subtype of cervical malignancy that presents with clinicopathological features mimicking other types of cervical cancer, leaving no established treatment protocols available. This report describes a case of a 50-year-old woman in perimenopause who presented with an increase in vaginal discharge, discomfort in the external genitalia, and bleeding after intercourse. The imaging examination revealed a cervical mass accompanied by enlarged lymph nodes in the pelvic cavity. A cervical biopsy confirmed adenocarcinoma, with an initial clinical stage classified as International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIA1. The patient underwent a radical hysterectomy and pelvic lymph node dissection (PLND), during which it was found that the tumor had involved pelvic lymph nodes. The revised staging was Stage IIIC1. According to the postoperative pathologic analysis, the woman was diagnosed as adenocarcinoma with a poorly differentiated grade and with myoepithelial differentiation features. Immunohistochemical analysis supported the diagnosis of the SMARCA4-deficient adenocarcinoma that was accompanied by high-grade squamous intraepithelial lesion (HSIL) in its surroundings, indicating the presence of two distinct types of lesions. Postoperative review after one month revealed multiple lymph node metastases in the left neck. Pathological examination confirmed it as distant metastasis from cervical adenocarcinoma, ultimately leading to a diagnosis of pT1N1M1 (IVB stage) cervical cancer. Following a six-cycle treatment regimen with cadonilimab, paclitaxel, and cisplatin, the lymph nodes in the neck demonstrated a significant reduction, indicating a preliminary positive response. In this case, SMARCA4-deficient cervical adenocarcinoma was characterized by significantly high invasive potential, early metastasis, and heterogeneity, indicating the significance of early detection and molecular pathological diagnosis in guiding personalized treatment strategies. Immunotherapy combined with chemotherapy may offer a new therapeutic approach for this rare type of cancer.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12957-025-04030-7.

Atypical glandular cells (AGC) in cervical cytology, as defined by the Bethesda System, indicate nuclear atypia beyond reactive changes but without definitive features of malignancy. Although clinically significant because it prompts follow-up procedures, no quantitative threshold exists for AGC diagnosis. This study evaluated whether the volume of glandular cell clusters (GCC), regardless of atypia, influences AGC interpretation and may contribute to unnecessary sampling. Following IRB approval, all cervical cytology cases diagnosed as AGC between January 2014 and June 2024 were retrieved, along with 100 random negative for intraepithelial lesion or malignancy (NILM) cases, and were manually re-screened with quantification of glandular cell clusters (GCC) defined as a group of ≥ 6 cohesive glandular cells irrespective of origin (endocervical versus endometrial) and the results were correlated with follow-up findings including endocervical and endometrial sampling. Of 301 AGC cases, 186 cases had slides available for review and follow-up data; two were excluded due to unsatisfactory quality. Eight cases were reclassified as unsatisfactory because of insufficient squamous cells and absence of atypia, most of which exhibited high GCC (mean 59). Notably, 140 cases (76.6%) showed no significant glandular pathology on follow-up, and in 111 cases (60.6%) the follow-up was negative. Overall, increased GCC correlated significantly with AGC interpretation compared to NILM cases (p = 0.01), even when histologic follow-up was negative. Higher GCC volumes may influence AGC diagnoses, even in cases lacking true cytologic atypia, potentially leading to unnecessary interventions. Greater awareness of this tendency and adherence to established cytologic criteria may improve diagnostic precision within the AGC category.

This case report describes a 75-year-old female who presented with generalized tiredness and neck swelling, initially raising suspicion of a primary thyroid malignancy. Fine-needle aspiration of the thyroid nodule was suspicious for malignancy (Bethesda Category V). Further evaluation revealed an inflammatory mass lesion in the right breast which was clinically diagnosed as inflammatory carcinoma and multiple enlarged lymph nodes including axillary, cervical, supraclavicular, and inguinal nodes. Immunocytochemistry on fine needle aspiration cytology (FNAC) and biopsies and immunohistochemistry of the breast lesion and lymph nodes in the patient ultimately revealed disseminated High-Grade Non-Hodgkin Lymphoma (NHL), Diffuse Large B-Cell Lymphoma (DLBCL) type. This case highlights the diagnostic challenges linked to atypical presentations of lymphoma mimicking other primary malignancies of solid organs.

The study aims are to evaluate the utility of cervical or vaginal human papillomavirus (HPV) status in predicting recurrence of noncervix lower genital tract (LGT) high-grade squamous intraepithelial lesion (HSIL), assess factors associated with HPV positivity, and explore patterns of HSIL surveillance. This retrospective cohort included patients undergoing ≥12 months of surveillance after biopsy-proven vulvar, vaginal, or anal HSIL between 2015 and 2023 at an Australian hospital with a laboratory that performs universal p16 and p53 immunohistochemistry for vulvar squamous neoplasia. Data collected included demographics, HPV results, medical comorbidities, vulvar dermatoses, treatment, frequency of surveillance, outcomes, and follow-up duration. Data were stratified by HPV status at the time of LGT HSIL diagnosis. Of 143 patients with a median age of 54 years, 23% used topical steroids for lichen sclerosus or planus, 93% had a recent or concurrent HPV test, and 53% of these were positive. Positive HPV was more frequent in vaginal versus vulvar HSIL (92% vs 46%; p = .003) and less frequent in patients with diabetes (23% vs 3%; p < .001). Recurrent or persistent HSIL occurred in 65%. HPV positivity was not associated with overall recurrence, but afforded a 6-fold higher vaginal HSIL recurrence risk. There was a documented surveillance strategy in 92% with 78% of these having 6-monthly assessments for 5 disease-free years, then annually. Cervical or vaginal oncogenic HPV results do not predict vulvar HSIL recurrence but may inform surveillance for vaginal disease. Limitations include the retrospective design, potential referral bias, and limited generalizability.

Multicentric, human papillomavirus (HPV) associated lower genital tract disease includes preinvasive and invasive lesions at multiple anatomic sites and can be synchronous or metachronous. Identifying patients with multicentric disease is crucial because of associated high treatment failure and recurrence. This study evaluates clinicopathologic patterns in immunocompetent and immunocompromised patients with multicentric lower anogenital disease. Two-hospital retrospective study of 36 patients with histologic diagnoses of multicentric anogenital HPV-associated dysplasia was identified over a 25-year period. Patients were classified based on immune status: immunocompetent without HIV, immunocompetent with HIV, and immunocompromised. Histologic diagnoses, p16 immunohistochemistry (IHC), and in situ hybridization (ISH) for high-risk (HR) and low-risk (LR) HPV were reviewed. The most common sites of dysplasia were the anus (25%) and vulva (25%), with high-grade squamous intraepithelial lesions (HSIL) being the most frequent diagnosis (50%). Positive p16 IHC and HR-HPV ISH staining occurred in 71% and 81% of specimens, respectively. One-third of patients revealed a variation in IHC/ISH expression in lesions at the same anatomic sites at different time points. A significantly higher frequency of variation occurred in individuals living with HIV and immunocompromised individuals when compared to immunocompetent individuals. This study supports the theory that some multicentric disease may arise from repeated infections with various HPV genotypes. The findings highlight the need for further research into genetic predispositions and other factors influencing the development of multicentric HPV-associated lesions in both immunocompetent and immunocompromised individuals.

ObjectiveTo improve human papilloma virus (HPV) screening, more effective triage methods for HPV-positive samples need development and validation. Cytology, the most common triage method today, is subjective and can only be applied to professionally collected samples. Methylation status has been shown to be informative, as genes are highly methylated in HPV-induced cervical dysplasia and cancer. This study aimed to assess whether triaging HPV-positive samples using molecular methods, such as methylation and genotyping for high-risk HPV types, could be as effective as cytology in cervical screening.MethodsA retrospective biobank study was conducted on HPV-positive samples collected in 2017–2018, analyzing FAM19A4/MiR-124-2 hypermethylation and HPV genotyping for types 16, 18, 31, 33, 45, 52, and/or 59, comparing these results to cytology triage for detecting histologically confirmed high-grade squamous intraepithelial lesions (HSIL) and cancer.ResultsResults from 1915 positive screening samples were analyzed, including 1052 follow-up biopsies with 402 HSIL or cancer cases. Genotyping showed slightly higher sensitivity than cytology but lower specificity, while methylation had higher specificity but much lower sensitivity. Cytology’s positive predictive value (PPV) was 36%, with lower PPVs for the molecular methods. Combining molecular methods increased the PPV but significantly reduced sensitivity.ConclusionsBased on these findings with molecular methods reducing sensitivity, we do not recommend adopting the molecular triage methods evaluated in this study in the Swedish setting. The trade-off between sensitivity and specificity does not support a change from the current cytology-based triage approach.

Timely treatment of anal high-grade intraepithelial lesions (HSIL) prevents progression to anal cancer. Available screening tools (anal Pap test and high-risk human papillomavirus testing) have inconsistent and suboptimal performance, often leading to overreferral to high-resolution anoscopy, the gold standard test for HSIL diagnosis. We aimed to develop and externally validate a clinical prediction model for histologic HSIL to improve triage to high-resolution anoscopy among individuals at increased risk for anal cancer. Medical records from 2 institutions were reviewed to identify candidate predictors of histologic HSIL. A penalized logistic regression model with elastic net regularization was developed and internally validated with five-fold cross-validation. External validation was performed in a third institution cohort. Candidate predictors were age, sex, HIV status, history of anogenital HPV-related disease, immunosuppressant use, anal cytology, anal high-risk HPV (hrHPV) status, and interaction terms (HIV status*hrHPV infection) and (HIV status*history of anogenital HPV-related disease). The derivation dataset included 536 patients, 382 (71.3%) were people living with HIV, 168 (31.3%) were women, and HSIL prevalence was 21.1%. The area under the ROC on the derivation dataset was 0.80 (95% CI = 0.69; 0.90). The external validation dataset included 242 patients, 159 (65.7%) people living with HIV, 18 (7.4%) women, with HSIL prevalence of 37.2%. The final model included age, sex, anal cytology, anal hrHPV, immunosuppressant use, history of anogenital HPV-associated disease, and the 2 interaction terms. The area under the receiver operating characteristic (ROC) on the external validation dataset was 0.73 (95% CI = 0.67; 0.80). This clinical prediction model demonstrated a promising performance and included objective factors that are easily obtained.

Objective To compare the effects of focused ultrasound (FUS) and loop electrosurgical excision procedure (LEEP) on cervical morphology and elasticity after treatment of cervical squamous intraepithelial lesions (SILs). Methods Eighty-one patients with histologically confirmed SILs (42 FUS vs. 39 LEEP) were prospectively evaluated. FUS ablation was performed using the CZF-2 device (Haifu® Medical, 3.5 MHz). LEEP followed ASCCP guidelines with resection margins ≥5 mm beyond lesions. Serial transvaginal ultrasound measurements (cervical length/width/volume) were conducted at baseline and 3/6 months postoperatively. Results At 3–6 months after surgery, the high-risk human papilloma virus (HR-HPV) clearance rate and high-grade SIL cure rate were similar in the FUS and LEEP groups (p > 0.05). Cervical length, width, anterior-posterior diameter, and volume did not significantly change after FUS (p > 0.003125). All 4 dimensions were significantly reduced after LEEP (p < 0.003125). These morphological alterations were greater in the LEEP group (p < 0.05). Strain rates at the internal and external os, and anterior-posterior lips did not significantly change after FUS (p > 0.05). After LEEP, strain rates slightly decreased at the internal and external os (1.02 ± 1.00 vs. 0.79 ± 0.69, p > 0.05) and significantly decreased at the anterior-posterior lips (1.43 ± 1.34 vs. 0.97 ± 0.93; p < 0.05). Conclusion FUS and LEEP demonstrate comparable efficacy in treating HR-HPV-associated SILs. Initial observations suggest that FUS impacts cervical morphology and elasticity less than does LEEP, implying an advantage of FUS for fertility preservation, although the long-term fertility outcomes require further investigation.

Background: In case of thyroid lesion conventional FNAC (C-FNAC) is most reliable and convenient investigation. But it has high inadequate sample collection rate. Ultrasound guided FNAC (US-FNAC) one of the alternative to investigate a thyroid swelling more appropriately. Objectives: Aim of this study to evaluate the diagnostic precision of C-FNAC and weigh up with US-FNAC as well as histopathology. Methods: In this study, a total of 200 patients divided into two groups (A&amp; B) presenting with thyroid swelling or nodules underwent C-FNAC for group A and US-FNAC for group B with subsequent surgery from January 2022 to December 2023 at Green Life Hospital. Cytological diagnosis was classified according to the Bethesda classification. Final histopathological results were compared to find out the accuracy of C-FNAC and US-FNAC. Results: From group A we found 7% nondiagnostic and in group B 1% due to inadequate sample. In term of sensitivity, C-FNAC counted 66.7% and US-FNAC 85.2% and in specificity it was 92.8% and 98.6% respectively. In C-FNAC false negative rate was 33.3% where it was 14.8% in US-FNAC. Finally the accuracy was 95% in US-FNAC where it was 85% in C-FNAC. Conclusions: C-FANC is very simple and useful tool for diagnosis of thyroid lesion. But for more precise and specific diagnosis US-FNAC is more superior due to additional information gathered from ultrasound examination along with well visualized aspiration from the targeted lesion. Bangladesh J Otorhinolaryngology 2025; 31 (1) Page-28-34

Background/Objectives: This study aimed to evaluate the effectiveness of core needle biopsy (CNB) by comparing its diagnostic yield to fine needle aspiration cytology (FNAC) across primary and secondary examinations. Methods: This retrospective review analyzed medical records of patients who visited Soonchunhyang University Cheonan Hospital between January 2021 and August 2023 for thyroid nodule evaluation. Demographic data and the malignancy risk of thyroid nodules were collected based on the 2021 Korean Thyroid Imaging Reporting and Data System. FNAC and CNB results, classified using the Bethesda system for reporting thyroid cytopathology and diagnostic categories for thyroid CNB, were categorized as either “conclusive” or “inconclusive.” The rates of conclusive results in the primary examination and nodules transitioning from inconclusive to conclusive results during the secondary examination were analyzed. Finally, the diagnostic yields of FNAC and CNB were assessed using histopathological findings from surgically excised nodules. Results: The rate of nodules classified as “conclusive” was significantly higher in the CNB group than that in the FNAC group. Among nodules subjected to secondary examination, only the group with FNAC followed by CNB demonstrated a significant improvement in the rate of transition from inconclusive to conclusive results. Although FNAC and CNB showed comparable sensitivity and accuracy, the specificity of CNB was greater than that of FNAC. Conclusions: This study confirms the clinical utility of CNB by demonstrating its higher rate of conclusive results than FNAC. Future prospective studies, including cost–benefit analyses, are warranted to further define the indications for CNB.

BackgroundAlthough minor cytological abnormalities predict a low risk of high-grade lesions, their high reporting rates lead to a considerable number of high-grade lesion cases. We carried out this study to analyze the immediate risk and 5-year cumulative risk of high-grade cervical lesions in high-risk human papillomavirus (Hr-HPV)-positive patients with minor cytological abnormalities and to investigate the clinical significance of minor cytological abnormalities during follow-up in our single-center.MethodsA total of 1892 patients with positive Hr-HPV, cytology result of atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL) and also underwent colposcopy and biopsy were selected to analyze the immediate risk of high-grade cervical lesions. Besides, a total of 832 patients with baseline histological results of CIN1 or below and 5-year follow-up data available were further used to analyze the 5-year cumulative risk of high-grade cervical lesions.ResultsThe immediate incidence rates of CIN3 + in the ASC-US and LSIL groups were 6.27% (63/1005) and 5.64% (50/887), respectively. When CIN3 + was used as the study endpoint, the multivariate logistic regression analysis indicated that there was no significant difference in either the immediate risk or the 5-year cumulative risk of CIN3 + between the ASC-US and LSIL groups.ConclusionsIn summary, since both the immediate and 5-year follow-up risks for CIN3 + were similar in patients with ASC-US and LSIL, routine follow-up should be performed in minor cytological abnormalities, regardless of whether the cytology result is ASC-US or LSIL. Through the risk assessment of Hr-HPV and cytology combined screening, the 2019 ASCCP guidelines were suitable for cervical cancer screening at our single center.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12885-025-14972-6.

While HPV vaccination and Pap screening have advanced cervical cancer (CCa) prevention, high-grade squamous intraepithelial lesions (HSIL) remain common, particularly among individuals with metabolic comorbidities like diabetes and hypercholesterolemia. Statins, commonly used for lipid control, possess anti-inflammatory and antiproliferative properties that may offer protective effects against cervical dysplasia. We explored the association between statin use and lesion grade in a population of dysplasia patients, and whether effects vary by comorbidity and race. Cross-sectional, observational retrospective analysis of electronic health records and billing data for 2,378 non-Latina/e (nL) Black and nL white patients diagnosed with LSIL or HSIL between 2014 - 2021 at a large academic medical center. Logistic regression assessed associations between statin use, comorbidity profiles (diabetes, hypercholesterolemia), race, and HSIL vs. LSIL, adjusting for potential confounders. Interaction terms were tested to evaluate effect modification. Statin users had significantly lower odds of HSIL than nonusers (adjusted OR=0.48, p<0.0001), despite being older, with higher comorbidity rates. Predicted HSIL probabilities ranged from 4% - 20% in statin users versus 13% to 29% in nonusers. The lowest risk was observed among diabetic patients on statins, particularly among nL Black patients, suggesting a possible synergistic protective effect in metabolically vulnerable populations. Only 35% of patients with a hypercholesterolemia diagnosis listed were on statins. Statin use was associated with substantially lower HSIL risk, particularly among nL Black patients with diabetes. These findings support further investigation of statins as a potential low-cost chemopreventive tool for cervical dysplasia, especially in populations with metabolic dysfunction.

BackgroundA diagnosis of atypical glandular cells (AGC) on Papanicolaou (Pap) slides is rare but has clinically significant findings associated with high‐risk cervical and endometrial lesions. The authors evaluated the efficiency and diagnostic performance of an artificial intelligence (AI)‐assisted platform (Riuqian WSI‐2400; with the registered trademark AICyte) in identifying AGCs on Pap slides.MethodsA retrospective analysis of 485 Pap cases was conducted, including 185 cases with AGCs, 50 cases with high‐grade squamous intraepithelial lesions, 50 cases with low‐grade squamous intraepithelial lesions, and 200 negative cases; of these, 264 cases had histologic correlations. An experienced cytopathologist reviewed all slides using conventional microscopy and AICyte. Then, the same cases were evaluated by two other pathologists using the AICyte system.ResultsThe initial study demonstrated a kappa value of 0.744, which indicated strong agreement of the Pap interpretation from the same pathologist between using microscopy and AICyte methods, whereas the average interpretation time was significantly reduced with AICyte (137 vs. 44 seconds). Diagnostic consensus among three pathologists using the AICyte system was strong, with a Kendall W coefficient of 0.802. The AICyte‐pathologist consensus reached an exact match with original interpretations in 95.1% of cases. AICyte‐assisted interpretations demonstrated improved specificity and diagnostic accuracy for glandular lesions compared with original interpretations while maintaining 100% sensitivity and negative predictive value.ConclusionsTo the authors' knowledge, this is the first study focusing on assessment of AGCs on an artificial intelligence system. The findings demonstrated that the AICyte system offers substantial improvements in efficiency and diagnostic consistency for the interpretation of AGCs and significantly reduces slide reading time. These results support the potential of AI to augment performance, especially in resource‐limited settings or high‐volume screening environments.

Photodynamic therapy for high-grade squamous intraepithelial lesions: A randomized controlled trial.

The clinical necessity of lymph node dissection in papillary thyroid carcinoma (PTC) surgery remains contentious. This study compared four logistic regression (LR) models (with distinct feature selection strategies) and four machine learning (ML) models to preoperatively predict lymph node metastasis (LNM) risk in PTC patients, with emphasis on multidimensional evaluation and cross-populational generalizability. Data from 3,175 PTC patients (2021 cohort) were randomly split into training (70%) and testing (30%) subsets, with external validation performed using a Chinese (2024, n = 104) and a Canadian (2019–2022, n = 412) cohort. Twelve predictors were screened, and models were evaluated using metrics of discrimination (AUC), calibration (Brier Score), classification accuracy, and clinical utility. The prevalence of LNM was 34.48%, 36.54%, and 30.10% in the internal, Chinese, and Canadian cohorts, respectively. Among ML models, Random Forest achieved the highest internal AUC (0.767), whereas XGBoost demonstrated superior generalization (external AUCs: 0.785 and 0.725). LR models, particularly BestSubset-GLM, outperformed these ML models with an internal AUC of 0.770 and external AUCs of 0.831 and 0.785. Notably, BestSubset-GLM exhibited high specificity (0.86), precision (0.59), favorable calibration (Brier Score < 0.20), and robust clinical utility across the approximately 15–90% threshold probability range. Extrathyroidal extension, tumor size above 1.00 cm, younger age, and male gender were identified as key LNM risk factors. Bethesda classification and molecular aberrations were integrated into models. BestSubset-GLM balanced parsimony, interpretability, and generalizability, thereby supporting clinical decision-making through dynamic nomograms. Comprehensive evaluation beyond AUC is crucial.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-19345-4.

BackgroundCervical cancer, prevalent in low- and middle-income countries, is primarily caused by high-risk HPV16. Vesicle-Associated Membrane Protein 8 (VAMP8), involved in vesicle trafficking and autophagy, may influence HPV16-related cervical cancer progression.MethodsVAMP8 expression was evaluated in cervical tissue specimens from patients with HPV16-positive lesions (including low- and high-grade squamous intraepithelial lesions and cancer) and HPV-negative normal controls using proteomics, qPCR, and immunohistochemistry. A Cox proportional hazards model for prognosis was developed using immunohistochemical data from a cohort of cervical cancer patients. The clinical significance of VAMP8 was further assessed using RNA-seq and clinical data from The Cancer Genome Atlas-Cervical Cancer (TCGA-CESC) cohort. The effects of VAMP8 on autophagy and tumor progression were examined in HPV16 E6/E7-immortalized cervical epithelial cells (Ect1/E6E7) and cervical cancer cell lines (SiHa, HeLa, C-33A) in vitro, and in a SiHa xenograft model in vivo. Transcriptomic analysis of Ect1/E6E7 and SiHa cells identified VAMP8-regulated pathways. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays in SiHa cells were used to confirm the regulation of the HIF-1 pathway.ResultsVAMP8 was upregulated in HPV16-positive samples, particularly in low-grade squamous intraepithelial lesions (LSIL). Elevated VAMP8 correlated with poor survival outcomes and advanced tumor stages. VAMP8 enhanced autophagy and reduced proliferation and invasiveness in HPV16-positive cervical cells but increased in established cancer cell lines. In vivo, VAMP8 overexpression promoted tumor growth and autophagy. The HIF-1 pathway emerged as a key regulatory axis of VAMP8, enhancing hypoxic responses and angiogenesis.ConclusionElevated VAMP8 in HPV16-associated cervical cancer promotes tumor progression by enhancing autophagy via the HIF-1 pathway, suggesting its potential as a diagnostic and prognostic biomarker.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12916-025-04378-3.

Background/Objectives: Accurate identification of vulvar high-grade squamous intraepithelial lesions (HSIL) is essential for preventing progression to invasive squamous cell carcinoma. This study addresses the gap in artificial intelligence (AI) applications for vulvar lesion diagnosis by developing and validating the first convolutional neural network (CNN) model to automatically detect and classify HPV-related vulvar lesions—specifically HSIL and low-grade squamous intraepithelial lesions (LSIL)—based on vulvoscopy images. Methods: This bicentric study included data from 28 vulvoscopies, comprising a total of 9857 annotated frames, categorized using histopathological reports (HSIL or LSIL). The dataset was divided into training, validation, and testing sets for development and assessment of a YOLOv11-based object detection model. Results: The CNN demonstrated a recall (sensitivity) of 99.7% and a precision (positive predictive value) of 99.1% for lesion detection and classification. Conclusions: This is the first AI model developed for detecting and classifying HPV-related vulvar lesions. The integration of such models into vulvoscopy could significantly improve diagnostic accuracy and positively impact women’s health by reducing the need for potentially invasive and anatomy-altering procedures.

BackgroundCervical cancer, linked to HPV and dysglycemia, lacks clarity on their combined impact. This study explores Ki-67’s role in mediating HPV and dysglycemia effects on cervical cancer risk.MethodsThis study enrolled patients with abnormal cervical cancer screening results, undergoing colposcopy and conization at Fujian Maternity and Child Health Hospital’s Cervical Disease Center from June 2018 to June 2023. Statistical analyses compared baseline characteristics across cervical lesion categories. Multinomial logistic regression examined HPV and dysglycemia associations with LSIL (low-grade squamous intraepithelial lesions), HSIL(high-grade squamous intraepithelial lesions), and cervical cancer, highlighting interaction and mediation analyses involving Ki-67.ResultsA total of 4,115 participants were included: 573 with hyperglycemia, 1,479 with HPV only, and 548 with both HPV and hyperglycemia. Prediabetes and diabetes significantly increased cancer risk (OR: 2.47, 95% CI: 1.75-3.47 and OR: 3.67, 95% CI: 2.41-5.6, respectively). Coexisting hyperglycemia further elevated cervical cancer risk by over three-fold (OR: 3.12, 95% CI: 2.34-4.16) compared to HPV-positive normoglycemics. A significant interaction between hyperglycemia and HPV infection was observed (AP (attributable proportion): 0.69, 95% CI: 0.61-0.77, p<0.001; SI (synergy index): 3.27, 95% CI: 2.5-4.27, p<0.001). Ki-67+ expression accounted for 39.84%, 37.35%, and 55.18% of the total effect of hyperglycemia, HPV, and their combined impact, respectively. Additionally, the combination of dysglycemia and HPV had a significant indirect effect on Ki-67 levels (estimate: 0.08, 95% CI: 0.06- 0.09, p<0.001).ConclusionsDysglycemia and HPV infection synergistically elevate cervical cancer risk, possibly influenced by Ki-67. Effective screening and management for both are vital in prevention. Further research is required to validate findings and elucidate molecular mechanisms.