BLBoning Li
Papers(2)
Risk‐stratified manag…25‐hydroxycholesterol…
Collaborators(4)
Long SuiLihua QiuLu ZhangShibo Jiang
Institutions(4)
Obstetrics And Gyneco…Beijing Obstetrics An…Soochow UniversityState Key Laboratory …

Papers

Risk‐stratified management of cervical high‐grade squamous intraepithelial lesion based on machine learning

AbstractThe concordance rate between conization and colposcopy‐directed biopsy (CDB) proven cervical high‐grade squamous intraepithelial lesion (HSIL) were 64−85%. We aimed to identify the risk factors associated with pathological upgrading or downgrading after conization in patients with cervical HSIL and to provide risk‐stratified management based on a machine learning predictive model.This retrospective study included patients who visited the Obstetrics and Gynecology Hospital of Fudan University from January 1 to December 31, 2019, were diagnosed with cervical HSIL by CDB, and subsequently underwent conization. A wide variety of data were collected from the medical records, including demographic data, laboratory findings, colposcopy descriptions, and pathological results. The patients were categorized into three groups according to their postconization pathological results: low‐grade squamous intraepithelial lesion (LSIL) or below (downgrading group), HSIL (HSIL group), and cervical cancer (upgrading group). Univariate and multivariate analyses were performed to identify the independent risk factors for pathological changes in patients with cervical HSIL. Machine learning prediction models were established, evaluated, and subsequently verified using external testing data.In total, 1585 patients were included, of whom 65 (4.1%) were upgraded to cervical cancer after conization, 1147 (72.4%) remained having HSIL, and 373 (23.5%) were downgraded to LSIL or below. Multivariate analysis showed a 2% decrease in the incidence of pathological downgrade for each additional year of age and a 1% increase in lesion size. Patients with cytology > LSIL (odds ratio [OR] = 0.33; 95% confidence interval [CI], 0.21–0.52), human papillomavirus (HPV) infection (OR = 0.33; 95% CI, 0.14–0.81), HPV 33 infection (OR = 0.37; 95% CI, 0.18–0.78), coarse punctate vessels on colposcopy examination (OR = 0.14; 95% CI, 0.06–0.32), HSIL lesions in the endocervical canal (OR = 0.48; 95% CI, 0.30–0.76), and HSIL impression (OR = 0.02; 95% CI, 0.01–0.03) were less likely to experience pathological downgrading after conization than their counterparts. The independent risk factors for pathological upgrading to cervical cancer after conization included the following: age (OR = 1.08; 95% CI, 1.04–1.12), HPV 16 infection (OR = 4.07; 95% CI, 1.70–9.78), the presence of coarse punctate vessels during colposcopy examination (OR = 2.21; 95% CI, 1.08–4.50), atypical vessels (OR = 6.87; 95% CI, 2.81–16.83), and HSIL lesions in the endocervical canal (OR = 2.91; 95% CI, 1.46–5.77). Among the six machine learning prediction models, the back propagation (BP) neural network model demonstrated the highest and most uniform predictive performance in the downgrading, HSIL, and upgrading groups, with areas under the curve (AUCs) of 0.90, 0.84, and 0.69; sensitivities of 0.74, 0.84, and 0.42; specificities of 0.90, 0.71, and 0.95; and accuracies of 0.74, 0.84, and 0.95, respectively. In the external testing set, the BP neural network model showed a higher predictive performance than the logistic regression model, with an overall AUC of 0.91. Therefore, a web‐based prediction tool was developed in this study.BP neural network prediction model has excellent predictive performance and can be used for the risk stratification of patients with CDB‐diagnosed HSIL.

25‐hydroxycholesterol inhibits human papillomavirus infection in cervical epithelial cells by perturbing cytoskeletal remodeling

AbstractPersistent high‐risk human papilloma virus (HR‐HPV) infection is the main risk factor for cervical cancer, threatening women's health. Despite growing prophylactic vaccination, annual cervical cancer cases are still increasing and show a trend of younger onset age. However, therapeutic approaches towards HPV infection are still limited. 25‐hydrocholesterol (25HC) has a wide‐spectrum inhibitory effect on a variety of viruses. To explore efficient interventions to restrict HPV infection at an early time, we applied different pseudoviruses (PsV) to evaluate anti‐HPV efficacy of 25HC. We tested PsV inhibition by 25HC in cervical epithelial‐derived HeLa and C‐33A cells, using high‐risk (HPV16, HPV18, HPV59), possibly carcinogenic (HPV73), and low‐risk (HPV6) HPV PsVs. Then we established murine genital HPV PsV infection models and applied IVIS to evaluate anti‐HPV efficacy of 25HC in vivo. Next, with the help of confocal imaging, we targeted 25HC activity at filopodia upon HPV exposure. After that, we used RNA‐seq and Western blot analysis to investigate (1) how 25HC disturbs actin cytoskeleton remodeling during HPV infection and (2) how prenylation regulates the cytoskeletal remodeling signaling pathway. Our findings suggest that 25HC perturbs F‐actin rearrangement by reducing small GTPase prenylation. In this way, the phenomenon of HPV virion surfing was restricted, leading to failed infection.

2Papers
4Collaborators