Colposcopy, a key procedure in cervical cancer screening for patients with abnormal TCT or HPV test results, requires extensive training for accurate diagnosis, yet diagnostic performance varies significantly across regions. This study presents Cervi-LLM, a multimodal MoE framework designed to assist in colposcopic detection by providing precise lesion localization and stratified diagnoses. The dataset included 126 cervical cancer, 692 HSIL, 306 LSIL, and 999 normal cases. Cervi-LLM integrates three core components: 1) YOLOMed for real-time, multi-scale segmentation of three staining modalities (saline, acetic acid, iodine); 2) joint fine-tuning of a LLM on both image features and clinical text using LoRA and progressive unfreezing; and 3) a two-level MoE architecture that fuses rule-based and data-driven expert outputs via dynamic gating, calibrated with clinical rules to deliver interpretable diagnoses (Normal/LSIL/HSIL( +)). In segmentation, Cervi-LLM achieved PA of 94.51% and meanIoU of 78.23%, outperforming U-Net (91.83%, 72.76%) and Polyp-PVT (93.69%, 75.34%). For three-class classification, it reached an overall ACC of 91.52%, exceeding junior physicians (65.88%) and senior physicians (76.57%). In detecting HSIL( +), it achieved sensitivity of 95.96% and specificity of 94.17%, compared to 67.58% and 81.67% for the senior physicians. The system processes images at approximately 30 fps and delivers a final diagnosis in 0.30 ± 0.05 min. Cervi-LLM effectively overcomes conventional colposcopy limitations, offering an accurate, real-time intelligent tool for cervical lesion screening and biopsy guidance.

Large cell neuroendocrine carcinoma (LCNEC) of the cervix is an uncommon and highly aggressive tumor. Diagnosis during pregnancy is especially difficult because physiological cervical changes and guideline-based restrictions on excisional procedures may limit detection of invasive disease. When LCNEC is concealed beneath surface adenocarcinoma in situ (AIS), routine punch biopsies may repeatedly miss stromal invasion, resulting in delayed recognition. Such presentations remain rarely documented and warrant attention due to their potential for rapid progression. A 28-year-old pregnant woman underwent colposcopy at 20 weeks of gestation for abnormal cervical findings. The first directed punch biopsy demonstrated AIS with high-grade intraepithelial changes. A second colposcopy at 34 weeks showed further enlargement of the visible lesion, yet the repeat punch biopsy again revealed only noninvasive disease. Because excisional diagnosis carries obstetric risks, no excision was performed during pregnancy. After cesarean delivery at 37 weeks, a third colposcopy performed during postpartum cervical involution showed partial resolution of pregnancy-related edema and eversion, although abnormal acetowhite and mosaic patterns persisted. A third postpartum punch biopsy remained noninvasive. Due to persistent discordance between the colposcopic appearance and biopsy results, a diagnostic loop excision was performed at 82 days postpartum. This revealed deeply invasive LCNEC located beneath surface AIS. Staging evaluation showed no residual or metastatic disease. The patient subsequently underwent radical hysterectomy with ovarian preservation and pelvic lymphadenectomy, followed by adjuvant platinum–etoposide chemotherapy, and remains disease-free to date. Review of pregnancy-associated LCNEC cases and population-level survival patterns suggests that earlier diagnosis and definitive treatment are associated with more favorable outcomes, whereas delayed diagnosis or advanced presentation carries markedly poor survival. This case shows that invasive LCNEC can remain hidden beneath adenocarcinoma in situ during pregnancy, resulting in repeated false-negative biopsies despite progressive clinical findings. In pregnant patients with persistent mismatch between colposcopic impressions and biopsy results, early postpartum excisional evaluation should be considered to avoid missing an aggressive malignancy.

To evaluate the efficacy and safety of 5-aminolevulinic acid photodynamic therapy (5-ALA PDT) for cervical squamous intraepithelial lesion (SIL). We systematically searched PubMed and other databases to compare the effectiveness of 5-ALA PDT with observation, ablation, and conization. Outcomes included overall response rate (ORR), complete remission (CR) rate, HPV clearance rate, and other relevant endpoints. Single-arm analyses were additionally performed by lesion grade. A total of 3,354 patients were included across 19 studies. The ORR with PDT was significantly higher than with observation (OR = 10.27, 95

Ovarian cancer (OC) is a fatal female malignancy, and Cisplatin resistance severely impacts the clinical management of epithelial ovarian cancer (EOC), the most prevalent histological subtype accounting for over 90% of cases. Exploration of novel effective targets and drugs for treatment of cisplatin-resistant EOC is urgently needed to address the tremendous challenge. In this study, we screened a Traditional Chinese Medicine (TCM) library including 978 monomers and found that Raddeanin A (RA) extracted from Anemone raddeana Regel displayed the powerful cytotoxic effect on cisplatin-resistant EOC cells. Further investigations revealed that RA had potential of inducing ferroptosis via binding to an evolutionarily conserved scaffold protein, VEPH1. Bioinformatics analysis combined with RA-sepharose pull-down assay and immunoprecipitation confirmed that RA interacted with two sites of VEPH1, site 1 (S1) at 212-217 aa and site 2 (S2) at 579-651 aa, and S1 was also involved in VEPH1 binding to and promoting lats1 activation. Moreover, RA bound to and enhanced VEPH1 degradation through the proteasome pathway, and meanwhile inhibited the interaction between VEPH1 and lats1, which in turn suppressed lats1 activation, promoted YAP nuclear translocation to up-regulate the expression of ferroptosis-driven proteins, TFRC and ACSL4, resulting in an imbalance of intracellular iron homeostasis, as well as promotion of lipid peroxidation, and thus inducement of ferroptosis in cisplatin-resistant EOC cells. Importantly, the in vivo results confirmed that RA induced ferroptosis and dramatically suppressed the growth of A2780/DDP transplanted tumours. Taken together, we revealed for the first time that VEPH1 is the direct target for RA, and ferroptosis contributes to RA-triggered anti-tumour effect on cisplatin-resistant EOC, which provides new insights into the therapeutic application of RA against EOC chemoresistance.

Background:Poly (ADP-ribose) polymerase inhibitors (PARPi) have improved outcomes in ovarian cancer with homologous recombination deficiency (HRD). However, approximately half of high-grade serous ovarian cancers retain intact homologous recombination repair and are classified as homologous recombination-proficient (HRP), limiting the clinical benefit of PARPi in this population. Strategies capable of pharmacologically inducing a functional HRD-like state may expand the therapeutic scope of PARPi. Methods:A drug repurposing screen of 97 FDA-approved targeted agents was conducted in olaparib-insensitive HRP ovarian cancer cell models. Drug interactions were evaluated using cell viability and colony formation assays. Homologous recombination activity was assessed using RAD51 foci formation and DR-GFP reporter assays. DNA damage, cell cycle distribution, and apoptosis were analysed using immunofluorescence and flow cytometry. Antitumour efficacy was evaluated in xenograft models. Immune recognition-related features and susceptibility to CD8+ T-cell-mediated killing in vitro were assessed using peripheral blood mononuclear cell (PBMC) coculture assays. Results:Proteasome inhibitors emerged as the most consistent sensitising drug class. The oral proteasome inhibitor ixazomib citrate demonstrated robust synergy with olaparib across multiple HRP ovarian cancer models. Mechanistically, ixazomib citrate disrupted recruitment of the homologous recombination protein RAD51 to DNA damage sites without reducing its expression, thereby inducing a functional HRD-like state consistent with BRCAness. This disruption increased olaparib-induced DNA damage, resulting in G2/M arrest and apoptosis. In xenograft models, combination therapy significantly suppressed tumour growth compared with either agent alone. Proteasome inhibition also increased tumour-surface MHC class I expression and appeared to enhance susceptibility to CD8+ T-cell-mediated tumour cell killing in vitro. Conclusions:Ixazomib citrate sensitised HRP ovarian cancer models to PARP inhibition by functionally impairing homologous recombination repair. These findings provide preclinical support for proteasome inhibition as a PARPi-sensitising strategy in HRP ovarian cancer. The immune-related observations are based primarily on in vitro coculture experiments and should therefore be considered exploratory. Further validation in additional preclinical and clinically relevant models is warranted.

Accurate segmentation of the placenta from multi-sequence MRI is pivotal for assessing the Placenta Accreta Spectrum (PAS), yet this endeavor poses formidable challenges: (1) the effective fusion of complementary information from disparate MRI sequences remains a non-trivial task, (2) the boundary between the placenta and the myometrium is often indistinct, a problem critically exacerbated by the spatial inaccuracies introduced during the upsampling phases of deep networks. To surmount these obstacles, we introduce the novel framework Uncertainty-guided Multimodal Fusion Network (UMM-Net). Our architecture, built upon a ConvNeXtV2 backbone, incorporates two key modules designed for targeted intervention. To resolve the challenge of fusion, we developed an Uncertainty-guided Multimodal Fusion (UMMF) module, which leverages cross-attention and pixel-level uncertainty to dynamically integrate data from T2 and bSSFP sequences. To enhance boundary definition, we created the Upsampling Displacement Error Correction (UDEC) module, which mitigates spatial artifacts by explicitly realigning feature maps. The network further embeds a lightweight Large-Receptive-Field Multi-Scale Context (LRF-MSC) module to capture a rich hierarchy of contextual information. Evaluation on our internal dataset shows that our proposed method achieves excellent performance, with a Dice of 0.9149, an IoU of 0.8532, and an HD95 of 2.7 mm. Through its network design, our fused network effectively solves the key issues of multi-sequence and boundary definition, while ensuring stable case segmentation accuracy, and still maintains a high level of performance in the face of PAS cases, verifying its strong robustness in helping clinical segmentation.

Persistent high-risk human papillomavirus (HR-HPV) infection drives cervical carcinogenesis, yet effective treatments for patients without histologically confirmed cervical lesions are lacking. Although five-aminolevulinic acid photodynamic therapy (ALA-PDT) effectively treats cervical lesions and associated HR-HPV, its efficacy for clearing HR-HPV in non-lesional patients is unclear. We aim to compare the efficacy of ALA-PDT versus interferon (IFN) in treating persistent HR-HPV infection in patients without cervical lesions. This real-world cohort study included 157 patients receiving three sessions of ALA-PDT and 114 patients receiving 3 courses total of IFN therapy. The primary outcome was HR-HPV complete clearance at 6- and 12-month post-treatment. At 6 months, complete clearance rates were 56.9% (82/144) in the PDT group versus 15.3% (13/85) in the IFN group (p < 0.001). At 12 months, rates were 67.0% (59/88) versus 28.3% (26/92) (p < 0.001). Generalized estimating equations (GEE) analysis confirmed PDT was significantly superior to IFN in reducing persistent infection risk (adjusted odds ratio [aOR] = 0.114, 95% CI: 0.054-0.242, p < 0.001). Longer infection duration (≥ 24 vs. 6-23 months) (aOR = 2.334, 95% CI: 1.352-4.030, p = 0.002) and increasing age (per year) (aOR = 1.025, 95% CI: 1.003-1.048, p = 0.027) were independently associated with higher persistence risk. Adverse events (mild pain and vaginal discharge) occurred in 5.1% of patients. ALA-PDT demonstrates superior and sustained efficacy over IFN for clearing persistent HR-HPV infection in patients without cervical lesions. Older age and longer infection duration are significant risk factors for treatment failure.

Abstract Prophylactic vaccines against oncogenic human papillomaviruses (HPVs) are effective in preventing HPV infection but not in treating existing HPV infection and cervical intraepithelial neoplasia (CIN). Current treatments for CIN are often ablative and may lead to long-term reproductive morbidity. Thus, there is a tremendous need for therapies that can treat the millions living with persistent oncogenic HPV infection and CIN and the risk of HPV-related cancers. RG002 is a mRNA-based therapeutic treatment targeting the E2, E6, and E7 proteins of HPV-16/18 with a targeted LNP for selective delivery to spleen and dendritic cells, which demonstrated excellent efficacy and safety in preclinical studies. In the phase I and expanded clinical studies, we evaluated the safety, efficacy, and immunogenicity of RG002 in 12 women with HPV 16/18 associated CIN2/3. Patients receive intramuscular administrations of 25, 75, 150, or 300 μg of RG002 at weeks 0, 2, and 4. RG002 does not cause any serious vaccine-related adverse events at any of the administered doses. Notably, all patients have exhibited complete regression of lesions and viral clearance within 17 weeks after the first dose, along with unprecedented E2/E6/E7 specific IFN-γ-producing T-cell response with clear dose-responses relationships. These initial data demonstrate the strong potential of RG002 as a first-in-class, non-surgical treatment for HPV-16/18-associated CIN2/3 to prevent progression to invasive carcinoma. Note on Study Status: *The initial cohort (n=12; 3 per dose) is nearing completion. Based on promising early results, the protocol has been amended to enroll an additional 15-30 patients by January 2026. Updated results from over 40 patients, including Week 17 efficacy data for at least 20 patients, are expected in mid-April 2026.* Citation Format: Shan Cen, Lan Zhu, Fei Chen, Wei Wang, Lihua Qiu, Hua Yang, Yijie Dong, Weiguo Zhang, Huizhen Zhang, Jing Wang. Rg002: An mRNA-LNP-based immunotherapy targeting HPV-16/18-related malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6703.

OBJECTIVE:To systematically evaluate the efficacy and safety of photodynamic therapy (PDT) for HPV-infected cervical intraepithelial neoplasia (CIN) based on randomized controlled trials (RCTs). METHODS:A systematic search was performed across PubMed, EMBASE, Web of Science, and the Cochrane Library from 2000 to 2025, targeting RCTs that compared PDT with standard conization methods or placebo. The primary outcomes assessed included histopathological response, human papillomavirus (HPV) clearance, and the rate of adverse reactions. The quality of the included RCTs was evaluated using the Cochrane Collaboration's RevMan 5.4.1 tool and meta-analysis was conducted to pool effect sizes. RESULTS:Of 270 retrieved records, 6 eligible RCTs involving 973 patients were included. Meta-analysis showed that PDT significantly improved lesion remission rate (OR = 2.27, 95% CI = [1.66, 3.11], I²=0, P < 0.05) and HPV clearance rate (OR = 1.99, 95% CI = [1.32, 2.99], I²=0, P = 0.05). No statistically significant difference in adverse reaction rate was observed between the two groups (P>0.05). CONCLUSION:Based on the pooled data of 6 RCTs, PDT is an effective and safe therapeutic option for HPV-infected CIN, as it enhances lesion remission and HPV clearance without substantially increasing adverse reactions.

Persistent 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.

Discrepancies have been found between preoperative colposcopic biopsy results and histology results of loop electrical excision procedure (LEEP) specimens. GynTect® is a six-methylation-marker assay that has demonstrated its potential as a triage tool for cervical lesion detection and prediction. The aim of this study was to evaluate the effectiveness of GynTect® in predicting the histology outcomes of post-LEEP specimens. A retrospective analysis was conducted to evaluate the clinical profiles, GynTect® results, and histology outcomes of postoperative specimens from 78 patients diagnosed with high-grade squamous intraepithelial lesion (HSIL) who underwent LEEP. The GynTect® assay is a six-marker (ASTN1, DLX1, ITGA4, RXFP3, SOX17, and ZNF671) methylation detection assay for cervical prep cell samples. Preoperative cervical cytology, high-risk human papillomavirus (hrHPV) detection, and methylation analysis were obtained from each participant. Preoperative colposcopic impression and biopsy results were recorded. Statistical analysis and multivariate logistic regression were performed using IBM SPSS Statistics 25. Among the negative-GynTect® patients, 19 cases (57.6

Significance Cervical high-grade squamous intraepithelial lesions (HSIL) often persist following incomplete excision during loop electrosurgical excision procedures (LEEP). Adjunctive photodynamic therapy (PDT) may enhance lesion clearance and HPV suppression. Approach A comparative study evaluated PDT following LEEP in HSIL patients with positive surgical margins. HPV clearance and disease regression were assessed at 3 months post-treatment. Statistical analysis used Fisher’s exact test. Results The PDT group (n=14) showed a 71.43% HPV clearance rate (10/14) compared to 55.56% (5/9) in the control group (P=0.4857). Disease regression was significantly higher in the PDT group, with 92.86% (13/14) achieving disease-free or downgraded status compared to 66.67% (6/9) in the control group (P=0.04545). Conclusions PDT as an adjunct to LEEP significantly improves disease regression in HSIL patients with positive margins, despite no significant impact on HPV clearance.

OBJECTIVE:This study aimed to evaluate the diagnostic performance of the novel Optoelectronic Imaging Tracing System as a triage or adjunct tool for women with high-risk human papillomavirus (hrHPV) infections. METHODS:Between June 2024 and August 2024, 581 women aged 18 to 65 years undergoing colposcopy were enrolled. The performance of hrHPV testing, cytology, the Optoelectronic Imaging Tracing System, and their combinations in detecting cervical intra-epithelial neoplasia grade 2 or worse and cervical intra-epithelial neoplasia grade 3 or worse was compared by assessing sensitivity, specificity, odds ratios, and area under the receiver operating characteristic curve (AUC). RESULTS:The Optoelectronic Imaging Tracing System demonstrated high sensitivity for detecting cervical intra-epithelial neoplasia grade 2 or higher (96.0%, 95% CI 93.5% to 98.6%) and grade 3 or higher (95.5%, 91.1% to 99.8%), and showed the highest odds ratios for detecting grade 2 or higher (26.0, 13.6 to 56.3) and grade 3 or higher (10.2, 3.72 to 43.3), respectively. In contrast, HPV16/18 genotyping had the highest specificity (65.9% [61.0% to 70.8%] and 63.7% [59.4% to 67.9%], respectively). In detecting cervical intra-epithelial neoplasia grade 2 or higher, the best AUC was achieved by the Optoelectronic Imaging Tracing System alone (0.742, 0.713 to 0.771), whereas the combination of the Optoelectronic Imaging Tracing System and HPV16/18 genotyping had the best AUC in detecting cervical intra-epithelial neoplasia grade 3 or higher (0.699, 0.645 to 0.753). No complaints or adverse events were reported by the participants. CONCLUSIONS:This exploratory study demonstrated the potential of the Optoelectronic Imaging Tracing System as a safe and effective triage or adjunct tool for detecting high-grade cervical lesions in women with hrHPV infections.

Backgroud Cervical cancer is one of the most common femal cancers. 5-ALA PDT is proven to be effective for the treatment of precancerous lesions. However, its role in cervical cancer treatment is poorly studied. Thus we aim to evaluate the effects of 5-ALA PDT on cervical cancer and its mechanism. Methods 5-ALA-derived PpIX accumulation in cervical cancer cell was mesured by flow cytometry. 24h after 5-ALA PDT, cytotoxicity assay was conducted, the cell death modalities were explored, and the different expresed genes was measured. Results PpIX accumulation was depended on 5-ALA conentration. After 5-ALA PDT, cytotoxicity assay revealed the IC50 was 250uM-8 J/cm2. Apoptosis was a main cell death modality.The occurance of ferroptosis also existed. A ferroptosis-related gene PRNP was inhibited. When we silenced PRNP, after 5-ALA PDT, the survival rate of sh-PRNP cells was significantly lowered. Conclusion 5-ALA PDT may induce ferroptosis by regulating PRNP expression in cervical cancer and exert antitumor effects.

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.

Metastatic 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.

Cervical cancer is the third most common malignancy among Chinese women in both incidence and mortality. Its progression is closely linked to complex interactions among immune cells within the tumor microenvironment (TME). As key components of the immune landscape, different T cell subsets play diverse and dynamic roles in shaping tumor immunity. This review provides a comprehensive overview of the roles of various T cell subsets in the TME of cervical cancer, with a focus on their distribution, functional heterogeneity, dynamic balance, and variations across different pathological subtypes and disease stages. We also highlight the intricate crosstalk between T cells and other immune cells in the TME and discuss recent advances in T cell-related immunotherapies for cervical cancer, including immune checkpoint inhibitors and HPV-targeted vaccines. By elucidating the roles of distinct T cell subsets and relevant immunotherapeutic approaches within the TME, this review provides insights into potential therapeutic targets and approaches for improving cervical cancer treatment and patient outcome.

Cervical cancer is the fourth most common malignancy among Chinese women,with approximately 150700 new cases and 55700 deaths reported in 2022,accounting for about 22.7％and 16％of the global inci-dence and mortality rates,respectively.1 Persistent high-risk human papillomavirus(HR-HPV)infection drives the progression of cervical intraepithelial neoplasia(CIN),with 20％-30％of CIN grade 2(CIN2)or worse cases progressing to invasive carci-noma without intervention.

Significance Persistent infection with high-risk HPV (hrHPV) is the primary cause of cervical cancer. Timely treatment of high-grade cervical intraepithelial neoplasia (CIN2/3) is essential to prevent cancer occurrence. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a minimally invasive treatment for CIN, preserving cervical structure and function. Approach 119 patients were randomly assigned to placebo, ALA 500mg, or ALA 750mg groups. Each participant received six local treatments with ALA or placebo and red light exposure at 7-14 day intervals. Outcomes were evaluated at 24 weeks via hrHPV testing, cytology, colposcopy, and biopsy. Results At 24 weeks, ALA 500mg (90%, P=0.022) and 750mg (95%, P<0.001) groups showed significantly higher lesion regression rates than the placebo group (69.2%). HrHPV clearance rates were also higher in both ALA groups (67.5% vs 33.3%, P<0.001). Conclusions ALA-PDT is a safe and effective treatment for hrHPV-related CIN2 with p16 positivity, with similar efficacy at both 500mg and 750mg concentrations.