Lihua Qiu

Fn14 Controls the SIRT2‐Mediated Deacetylation of Slug to Inhibit the Metastasis of Epithelial Ovarian Cancer

AbstractMetastatic spread of cancer is the leading cause of death in patients with epithelial ovarian cancer (EOC), and elucidation of the molecular mechanisms underlying this process is a major focus of cancer research. Fibroblast growth factor‐inducible 14 (Fn14) has been shown to regulate wound repair, inflammation, angiogenesis, and chemoresistance, but its functional role in metastasis in EOC is still unknown. Here it is reported that Fn14 is identified as a cancer metastasis suppressor that inhibits the migratory and invasive potential of EOC cells by down‐regulating epithelial‐mesenchymal transition (EMT). Mechanistically, it is identified that Fn14 promotes acetylation‐dependent protein degradation of Slug, a key transcriptional factor associated with EMT. The deacetylase Sirtuin 2 (SIRT2) has been reported to be involved in the deacetylation of Slug protein to stabilize it and then prevent its degradation in the nucleus. The results showed that Fn14 alters the subcellular localization of (SIRT2) by interacting with SIRT2, leading to reduced SIRT2 shuttling into the nucleus and subsequently promoting the acetylated degradation of Slug. Collectively, the work has demonstrated for the first time that Fn14 inhibits EOC metastasis by regulating SIRT2‐mediated Slug deacetylation, providing a new perspective and method for the development of future novel therapeutic strategies for the treatment of EOC metastasis.

Efficacy and safety of 5‐aminolevulinic acid‐based photodynamic therapy for cervical low‐grade squamous intraepithelial lesions with HPV infections

Abstract To assess the effectiveness and safety of 5‐aminolevulinic acid‐based photodynamic therapy (5‐ALA PDT) for cervical low‐grade squamous intraepithelial lesions (LSIL) patients with high‐risk human papillomavirus (HR‐HPV) infection and to investigate independent factors that influence the efficacy of PDT treatment. A retrospective analysis was conducted on 530 patients with pathologically confirmed LSIL and HR‐HPV infection, treated between March 2017 and January 2024. All patients underwent 5‐ALA PDT at an interval of 7–14 days, for a total of 3 to 6 sessions. Follow‐ups were conducted 3 and 12 months post‐treatment. The efficacy was assessed using HPV genotyping, ThinPrep cytology test (TCT) and colposcopy‐directed biopsy. The HPV remission rate was 52.08% at 3 months' follow‐up and increased to 69.84% at 12‐month follow‐up, surpassing the rate at 3‐month follow‐up ( p  < 0.001). The LSIL regression rate was 75.85% at 3 months' follow‐up and rose to 86.77% at 12‐month follow‐up, exceeding the rate at 3‐months' follow‐up ( p  < 0.001). Multivariate analysis revealed that single HPV infection (OR 2.296 [95%CI 1.550–3.402]) was an independent predictor of HPV remission after 5‐ALA PDT treatment. Single HPV infection (OR 1.690 [95% CI 1.077–2.652]), type III transformation zone (OR 3.094 [95% CI 1.899–5.041]), HPV remission after PDT treatment (OR 4.938 [95% CI 3.099–7.870]) were independent predictors of LSIL participants receiving total lesion regression after PDT treatment. Adverse reactions were all mild. 5‐ALA PDT is an effective and non‐invasive therapy for LSIL patients with HR‐HPV infection. Identifying predictors of treatment success may optimize patient selection, ultimately improving clinical outcomes.

Efficacy of different 5-aminolevulinic acid photodynamic therapy regimens in managing HSIL/CIN2 among reproductive-age women: A retrospective study

High-grade squamous intraepithelial lesion (HSIL) is a precancerous lesion that requires timely and effective intervention. Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) has emerged as a non-invasive, fertility-preserving alternative to excisional procedures. However, the ALA-PDT regimen remains to be optimized. To compare the efficacy and safety of three treatment strategies-three-session PDT (3PDT), six-session PDT (6PDT), and a single CO This retrospective cohort study included 158 women aged 20-45 years with biopsy-confirmed cervical HSIL/CIN2. Participants received one of three regimens: 3PDT (n = 49), 6PDT (n = 47), or Laser + 6PDT (n = 54). Lesion regression and high-risk HPV (hrHPV) clearance were assessed at 3-6 and 9-12 months post-treatment. A subset of patients was followed up to 18-24 months. Adverse events were also recorded. At the 3-6 months follow-up, the complete remission (CR) rates were 67.35 % (3PDT), 74.47 % (6PDT), and 79.63 % (Laser + 6PDT), with hrHPV clearance rates of 67.35 %, 72.34 %, and 77.78 %, respectively. Differences among groups were not statistically significant (P > 0.05). By 9-12 months, CR rates reached ≥90 % in all groups, and hrHPV clearance exceeded 80 %. At 18-24 months, hrHPV clearance reached 100 % in the 6PDT group, while three patients in the 3PDT group experienced HPV recurrence. All regimens were well tolerated, with only mild adverse events reported. All three ALA-PDT-based regimens were effective and safe in treating HSIL/CIN2 in reproductive-age women. Although not statistically significant, six-session PDT with or without laser pretreatment showed a trend toward higher lesion remission and hrHPV clearance. Individualized treatment decisions based on disease severity, patient preference, and cost factors are recommended to optimize outcomes.

Efficacy of ALA‐PDT in treating cervical low‐grade squamous intraepithelial lesions with high‐risk HPV patients: A multicentre randomized controlled trial

AbstractPersistent infection with high‐risk human papillomavirus (hrHPV) is a major cause of cervical cancer. Current management of low‐grade squamous intraepithelial lesions (LSIL) primarily involves monitoring, though some cases progress to cervical precancer or cancer, requiring timely intervention. This study aimed to evaluate the efficacy of 5‐aminolevulinic acid photodynamic therapy (ALA‐PDT) in treating cervical LSIL with hrHPV infection. A total of 155 women with LSIL and hrHPV infection were enrolled and randomly assigned to either the treatment group, which received six sessions of ALA‐PDT, or the control group, which underwent routine follow‐up. Outcomes were assessed at 6 and 12 months using hrHPV testing, cytology, colposcopy, and biopsy. Results showed that ALA‐PDT significantly improved lesion regression and hrHPV clearance rates at both 6 and 12 months. At 6 months, the lesion regression rate in the treatment group was 80.43% versus 56.10% in the control group (p = 0.0203), and the hrHPV clearance rate was 61.96% versus 29.27% (p = 0.0005). At 12 months, both rates remained significantly higher in the treatment group. Age was found to influence hrHPV clearance, with younger women (<45 years) showing significantly higher clearance rates. ALA‐PDT was well tolerated, with only minor side effects, such as localized pain and pruritus, reported. The study suggests that ALA‐PDT is a safe, effective, and non‐invasive treatment option for patients with cervical LSIL and hrHPV infection who require active intervention.

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.

Efficacy and influencing factors of CO2 laser, topical photodynamic therapy versus therapy combined with CO2 laser pretreatment for vaginal low-grade squamous intraepithelial lesions with high-risk HPV infection

Vaginal intraepithelial neoplasia (VaIN) is a group of diseases of squamous epithelial dysplasia and carcinoma in situ occurring in the vagina, which is associated with high-risk human papillomavirus (HR-HPV) infection. To evaluate the efficacy and safety of Carbon dioxide (CO Patients with HR-HPV infection and pathological diagnosis of VaIN1 and received laser or PDT or PDT combined with laser pretreatment were recruited. A total of 45 patients received one to three times CO There was no significant difference in regression rate of VaIN1 among the laser Group, the PDT Group and the laser + PDT Group (3-6 month follow-up: 57.78% vs 73.3% vs 80 %, 9-12 month follow-up: 68.89% vs 80% vs 86.67 %, P>0.05). HR-HPV remission rates were also similar in the three groups (3-6 month follow-up: 26.67% vs 46.67% vs 46.67 %, 9-12 month follow-up: 40 % in all groups, P>0.05). Compared to HR-HPV negative group, patients in the HR-HPV positive group were older and had more pregnancies. Menopause and multiple vaginal lesions were more common in the HR-HPV positive group. Adverse reactions were mild in the PDT Group. The laser Group and the laser + PDT Group had more adverse effects, such as increased vaginal secretion, vaginal bleeding, scarring and local pain. For patients with VaIN1 at risk of progression, ALA-PDT presents itself as a viable choice for those who are well-informed and can consent to its costs and benefits. The addition of CO

Epidemiology and analysis of potential risk factors of high‐risk human papillomavirus (HPV) in Shanghai China: A cross‐sectional one‐year study in non‐vaccinated women

AbstractData regarding human papillomavirus (HPV) prevalence, its associated risk factors, and women's knowledge about this disease before the HPV vaccine was approved are limited in Shanghai, China. Therefore, we investigated these questions among females in Shanghai and aimed to provide comprehensive data to guide HPV vaccination and present the biopsychosocial risk factors that impact high‐risk HPV infection, and evaluate the level of knowledge and awareness of this disease among women aged 21–65 years old. A total of 6619 (aged from 21 to 65) women from different communities volunteered to participate in the HPV screening and complete questionnaires from December 2016 to December 2017 in the Department of Obstetrics and Gynecology of nine hospitals in Shanghai. Data were analyzed using sample logistic regression to assess biopsychosocial risk factors that impact high‐risk HPV infection and knowledge of HPV infection. A total of 632 (9.5%) cases were positive for high‐risk HPV test, 22.6% of them were HPV 16/18 infection, 77.4% of them were non HPV 16/18 infection. 40 potential risk factors may be related to high‐risk HPV infection, and there were 19 factors' p value < 0.1 from single factor logistic analysis. Finally, multivariable regression revealed education level, type of vaginitis, history of hyperlipidemias, family history of cancer, number of pregnancies, number of sex partners were independent risk factors for high‐risk HPV infection (p < 0.05). When stratified by education level, women who finished graduate school had significantly greater knowledge of cervical cancer, cervical screening, and the relationship between HPV and cervical cancer than other groups (p < 0.05). The prevalence rate of high‐risk HPV was a little lower than other regions in China and other countries, which may be related to regions, races, living habits, and economy. A less reported finding is that the history of vaginitis and the history of hyperlipidemias in our study were related to HPV infection. The majority of the participants had poor knowledge regarding cervical cancer, cervical screening, and the relationship between HPV and cervical cancer. Hence, these results should be served as a wake‐up call for the government to increase knowledge and awareness via the media and doctors.

Effectiveness of photodynamic therapy with 5-aminolevulinic acid on HPV clearance in women without cervical lesions

High-risk HPV (hrHPV) not only increases the risk of cervical precancerous lesions and cervical cancer, but also adds psychological burden to HPV-positive women. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a non-invasive and highly tissue-selective therapy. We aim to investigate the clinical efficacy of ALA-PDT for elimination of cervical hrHPV infection in HPV-positive women without cervical lesions. A total of 57 hrHPV-positive women without pathologically proved cervical lesions received three treatments of ALA-PDT in total. HPV DNA testing and pap cytology were performed in all patients. Patients with positive HPV16/18 or abnormal TCT results received colposcopic biopsy during the follow-up. hrHPV clearance rate was 56.1 % (32/57) at 3-month follow-up and 68.1 % at 6-month follow-up. 100 % of HPV 18 and 87.5 % of HPV16 infections were cleared while the clearance rate was 48.8 % among those positive for 12 other high-risk types. Multivariate analysis showed HPV16/18 infection was associated with significantly higher clearance rate. HPV clearance rate in patients with multiple-type HPV infection was significantly lower than that in patients with single-type HPV infections. ALA-PDT is effective on treating hrHPV infection in patients with no cervical lesions. HPV16/18 positive cases can benefit most from ALA-PDT. Multitype-infected women need more sessions of 5- ALA-PDT to eradicate hrHPV infection.

The effect of local photodynamic therapy with 5-aminolevulinic acid for the treatment of cervical low-grade squamous intraepithelial lesions with high-risk HPV infection: A retrospective study

High-risk HPV infection is the main cause of cervical cancer and pre-cancerous lesions. The current principle of clinical management of cervical low-grade squamous intraepithelial lesion is observation for 2 years. Progression to high-grade squamous intraepithelial lesion warrants intervention. Primary treatment option is surgical excision which may have a negative impact on fertility. Topical photodynamic therapy is a non-invasive and targeted therapy. We investigated the clinical efficacy of this therapy for cervical low-grade squamous intraepithelial lesion with high-risk HPV infection. A retrospective study consisting of 258 female patients aged 21-69 years with a histologically confirmed cervical low-grade squamous intraepithelial lesion with high-risk HPV infection was carried out. Subjects were treated with three sessions of 20 % 5-aminolevulinic acid photodynamic therapy at intervals of 7-14 days. Three months after treatment, the effect was evaluated through HPV typing, Thinprep cytology and colposcopy directed biopsy. Six months after treatment, the photodynamic therapy effect was evaluated by HPV genotyping and Thinprep cytology first, the pathological examination would be performed at the 6-month follow-up point if the cytological results indicated the risk of high-grade squamous intraepithelial lesions. Three months after treatment, among 258 low-grade squamous intraepithelial lesion with high-risk HPV infection patients, total baseline HPV remission rates was 64.34 % (166/258). The remission rate of HPV16/18 group was not statistically significant compared to the HPV non-16/18 group (73.13 % vs 61.26 %, p = 0.081).The remission rates of the 50 age group (67.28 %vs46.34 %, p = 0.001). The total lesion regression rate wa treatment, among 258 low-grade squamous intraepithelial lesion with high-risk HPV infection patients, total baseline HPV remission rates was 64.34 % (166/258). The remission rate of HPV16/18 group was not statistically significant compared to the HPV non-16/18 group (73.13 % vs 61.26 %, p = 0.081).The remission rates of the 50 age group (67.28 %vs46.34 %, p = 0.001). The total lesion regression rate was 84.88 % (219/258). 12.8 % (33/258) of patients did not progress. Only 2.33 % (6/258) patients progressed to high-grade squamous intraepithelial lesion and accepted loop electrosurgical excision procedure. The patients >50 age group had significant higher progression rate than the patients ＜50 age group (p＜0.05). Six months after treatment, except for 6 patients who progressed to high-grade squamous intraepithelial lesion and underwent surgical treatment, the total baseline HPV remission rates was up to 82.54 % (208/252). 5-aminolevulinic acid photodynamic therapy was highly effective and did not appear to create cervical damage.. It might be an ideal treatment for cervical low-grade squamous intraepithelial lesion with high-risk HPV infection, but this requires additional clinical trials.

Feasibility study of 5-aminolevulinic acid mediated photodynamic therapy of persistent vaginal high-risk HPV infection of post-hysterectomy patients

Patients after hysterectomy are at higher risk for developing VaIN. However, there are no standard treatments for HPV infection and VaIN after hysterectomy and relative studies are limited. Thus we aim to evaluate the feasibility of 5-aminolevulinic acid photodynamic therapy (5-ALA-PDT) for the treatment of persistent vaginal infection with high-risk HPV (HR-HPV) in post-hysterectomy patients. Thirty-eight patients aged 43-70 years old with persistent vaginal stump HR-HPV infection with or without histological vaginal intraepithelial neoplasia (VaIN1) during follow-up after hysterectomy were recruited. Twenty patients received three times of ALA-PDT (PDT Group). Eighteen patients did not receive any treatments (Control Group). HPV testing, cytology, and colposcopy were performed in all patients 4-6 months and 12 months after treatment. HR-HPV remission rates of the PDT Group were 40% (8/20) and 66.67% (12/18) at the 4-6 month and 12-month follow-up, respectively, both were significantly higher than that of the Control Group (11.11% (2/18) and 6.23% (1/16), respectively; P < 0.05). For the PDT Group, the regression rate of VaIN1 was 100% (7/7) at 4-6 months, while VaIN1 recurred in two cases (28.6%) at the 12-month due to persistent HR-HPV infection. No persistence or progression of VaIN1 was noted. For the Control group, the spontaneous regression rate of VaIN1 was 50% (3/6) at 4-6 months and one patient progressed into VaIN2. At the 12-month follow-up point, one patient reccurred and the disease regression, persistence and recurrence rates were 40% (2/5), 40% (2/5) and 20% (1/5), respectively. Adverse reactions were mild after PDT treatment. 5-ALA-PDT is a safe, non-invasive, and effective option for post-hysterectomy patients who have persistent HR-HPV infection.

Chinese expert consensus on the clinical applications of aminolevulinic acid-based photodynamic therapy in female lower genital tract diseases (2022)

With the younger onset age of female lower genital tract diseases, there are increasing demands for protecting organ and tissue structures to preserve fertility and, therefore, effective fertility-sparing treatments that cause minimal normal tissue damage and less adverse reactions are urgently needed. This study is aimed at reviewing information and achieving consensus on recommendations on the clinical applications of aminolevulinic acid-based photodynamic therapy (ALA-PDT) in female lower genital tract diseases. Members of the expert panel held online and in-person meetings to discuss and revise drafts created by the steering committee based on the literature review and the clinical experiences of the expert panel. Opinions of the experts were transcribed and discussed in detail to ensure that the consensus statement best reflects the current advances in the field and the experts' view. After numerous rounds of meetings, experts unanimously agreed on the importance of ALA-PDT in the treatment of cervical squamous intraepithelial lesions (SIL), vaginal SIL, vulvar SIL, vulvar lichen sclerosus (VLS), and condyloma acuminatumon (CA). Experts also reached consensus on the recommended treatment regimen and treatment methods. This consensus aimed to provide practical basis and guidance for the clinical applications of ALA-PDT in female lower genital tract diseases in China. Of note, this is the only expert consensus prepared by board-certified specialists in gynecology and obstetrics in China. More evidence-based clinical studies should be made to update and expand the current recommendations.

Optimising cervical cancer screening during pregnancy: a study of liquid-based cytology and HPV DNA co-test

Abstract This study assessed the efficacy of ThinPrep cytologic test and human papillomavirus (HPV) co-test in cervical cancer screening during pregnancy. A cohort of 8,712 pregnant women from Ren Ji Hospital participated in the study. Among them, 601 (6.90%) tested positive for high-risk HPV (HR-HPV) and 38 (0.44%) exhibited abnormal cytology results (ASCUS+). Following positive HR-HPV findings, 423 patients underwent colposcopy, and 114 individuals suspected of having high-grade squamous intraepithelial lesion and cervical cancer (HSIL+) underwent cervical biopsy. Histological examination revealed 60 cases of normal pathology (52.63%), 35 cases of low‐grade squamous intraepithelial lesion (30.70%), 17 cases of HSIL (14.91%), and 2 cases of cervical cancer (1.75%). The incidence of HSIL+ in HPV 16/18 group was significantly higher than that in non-HPV16/18 group (10.53% vs. 6.14%, P &lt; 0.05). Subsequent evaluation of the clinical performance of cytology alone, primary HPV screening, and co-testing for HSIL+ detection revealed that the HSIL+ detection rate was lowest with cytology alone. These findings suggest that HPV testing, either alone or combined with cytology, presents an efficient screening strategy for pregnant women, underscoring the potential for improved sensitivity in cervical cancer screening during pregnancy. The significantly higher incidence of HSIL+ in the HPV16/18 group emphasizes the importance of genotype-specific considerations.