Ruifang Wu

One-year restoration of vaginal health: synergistic dynamics of microbiome and metabolome following the elimination of high-grade cervical intraepithelial neoplasia

ABSTRACT Therapeutic elimination of high-grade cervical intraepithelial neoplasia (CIN) is widely implemented for cervical cancer prevention. Despite the demonstrated dysbiosis of vaginal microenvironment in high-grade CIN, its post-therapy restorations remain to be poorly understood, especially in functional aspects. This study aimed to characterize temporal changes in both vaginal microbiota (VM) and metabolome (VMeta) following therapeutic elimination of high-grade CIN. We conducted a longitudinal study of 32 HPV-positive women with high-grade CIN who underwent therapeutic procedures. Vaginal swabs were collected at baseline (pre-therapy) and at 6- and 12-month follow-up visits for integrated VM and VMeta analysis. We observed a gradual restoration of Lactobacillus crispatus levels from baseline to 12 months ( P < 0.05). Concurrently, we detected significant decreases in dysbiosis-associated bacteria, including Prevotella bivia , Ureaplasma parvum , and Peptoniphilus sp. 6 months post-therapy compared to the baseline. VMeta analysis revealed distinct metabolic shifts across the follow-up periods. The early post-therapy phase (baseline to 6 months) was characterized by enrichment of glycerophospholipids and depletion of nucleotide metabolites, while the later phase (6–12 months) showed increases in flavonoids, lysophospholipids, bioactive amides, and amino acid metabolism. Integration of correlation and dynamic Bayesian network analysis indicated potential regulatory relationships and time-lag effects involving HPV infection, L. crispatus , Bifidobacterium sp., Streptococcus anginosus , Megasphaera sp., U. parvum, and those metabolites. This study enhances our understanding of a sequential restoration process post-therapy in the vaginal microenvironment. IMPORTANCE Therapeutic elimination of high-grade CIN is routine, yet functional recovery of the vaginal ecosystem is poorly defined. In a 12-month longitudinal multi-omics study of 32 women, we show stepwise restoration: progressive L. crispatus dominance with sustained decreases in dysbiosis-associated taxa ( P. bivia, U. parvum, Peptoniphilus ). Metabolically, an early rise in glycerophospholipids and fall in nucleotide metabolites is followed by later enrichment of flavonoids, lysophospholipids, bioactive amides, and amino acid derivatives. Correlation and dynamic Bayesian network analyses reveal putative regulatory links, time-lag effects, and downstream impacts of HPV clearance. These findings deliver a functional roadmap of post-therapy recovery, nominate measurable microbial–metabolite milestones and candidate biomarkers for monitoring, and suggest targets for adjunct interventions to accelerate re-establishment of protective states. This work informs precision follow-up in cervical cancer prevention programs.

HPV negative conversion following Hiporfin PDT for HPV associated HSIL in the female lower reproductive tract

Currently, there is no relevant literature specifically discussing the human papillomavirus (HPV) negative conversion rate following Hiporfin photodynamic therapy (PDT) in HPV-associated high-grade squamous intraepithelial lesion (HSIL) of the female lower reproductive tract. Our study aims to fill this gap. Prospective study of 91 patients aged 37.4 ± 13.2 years old with HSIL in the female lower reproductive tract (cervical HSIL: 55, vaginal HSIL: 25, cervical HSIL combined with vaginal HSIL: 8, cervical HSIL combined with vulvar HSIL: 1, vaginal HSIL combined with vulvar HSIL: 2). Hiporfin

Hiporfin-photodynamic therapy for high-grade squamous intraepithelial lesions of the endocervical canal in young women

The objective of this prospective study was to assess the efficacy of Hiporfin-photodynamic therapy (PDT) int the treatment of young women diagnosed with high-grade squamous intraepithelial lesions (HSIL) of the endocervical canal. This study included 14 patients aged 30 ± 4.2 years (range 21-37) with HSIL of the cervical canal, treated at our hospital from August 2021 to June 2023. Hiporfin (2 mg/kg) was administered intravenously and laser irradiation with a 630 nm wavelength was performed on the cervical canal and cervical surface 48-72 h later. All patients had been observed for at least 12 months. 64.3% (9/14) were nulliparous. The complete response (CR) rate of cervical canal involvement was 100.0% (14/14) at 3-6 months. Pre-PDT, all patients (14/14) tested positive for high-risk human papilloma virus (HR-HPV). The HPV eradication rate was 64.3% (9/14) at 3-6 months and 85.7% (12/14) at 12 months. No serious adverse effects were observed in patients during or after PDT. No recurrence was noted during the long-time follow-up. 6 patients who planned to get pregnant achieved 6 pregnancies including 1 spontaneous abortion, 2 term pregnancies, and 3 ongoing pregnancies. No fetal loss occurred due to cervical incompetence. Hiporfin-PDT may be a promising, fertility-preserving treatment for HSIL of the endocervical canal in young women.

Photodynamic therapy compared with loop electrosurgical excision procedure in patients with cervical high-grade squamous intraepithelial lesion

The study aimed to compare the effectiveness between Hiporfin-photodynamic therapy (PDT) and loop electrosurgical excision procedure (LEEP) in treating cervical high-grade squamous intraepithelial lesion (HSIL). We conducted a retrospective analysis of 104 women diagnosed with cervical HSIL at our hospital from April 2019 to July 2023. With 1:1 matched case-control, 52 cases received Hiporfin-PDT and 52 cases underwent LEEP. All PDT-treated cases received Hiporfin (2 mg/kg) I.V. and a diode laser at a wavelength of 630-nm. T-test, Chi-square test, Fisher's exact test, and Yates's correction for continuity were conducted for statistical. A P value < 0.05 was considered significant. The complete response (CR) post-PDT at 3rd-6th months,10th-12th months and 24th months was in 98.1% (51/52),100.0% (45/45) and 100.0% (22/22) patients respectively, compared to 98.1% (51/52), 100.0% (46/46) and 100.0% (24/24) patients respectively after LEEP. HPV clearance rates after PDT at 3rd-6th months,10th-12th months and 24th months was 76.9% (40/52), 88.9% (40/45) and 95.5% (21/22) respectively, compared to 69.2% (36/52), 93.5% (43/46) and 95.8% (23/24) respectively after LEEP, with no significant difference between the two groups (P = 0.508, P = 0.687 and P = 1.000, respectively). Postoperative complications in the PDT group were tolerable. The cure rates and HPV eradication of Hiporfin-PDT were comparable with that of LEEP in the management of cervical HSIL. Hiporfin-PDT may serve an alternative method for organ-saving in cervical HSIL.

Comparative analysis of photodynamic therapy and conization for cervical high-grade squamous intraepithelial lesion: A systematic review and meta-analysis

This review aims to compare the effectiveness of photodynamic therapy (PDT) with conization, including loop electrosurgical excision procedure (LEEP) and cold-knife conization (CKC), in treating cervical high-grade squamous intraepithelial lesions (HSIL). PubMed, Cochrane Library, Google Scholar, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched. The outcomes assessed were complete response (CR) rate, human papillomavirus (HPV) eradication rate, recurrence rate, and adverse events (AEs). 9 studies were included. A total of 312 patients received PDT, while 380 underwent conization (LEEP/CKC). There was no significant difference between PDT and conization in the CR rate at 3-6 months (OR: 1.64 [0.97, 2.76]; P = 0.06), 12-month CR (OR: 0.49 [0.13, 1.90]; P = 0.30), HPV eradication rate at 3-6 months (OR: 1.40 [0.95, 2.07]; P = 0.09), HPV eradication rate at 12 months (OR: 0.92[0.47, 1.82]; P = 0.81), or 12-month recurrence rate (OR: 2.97 [0.62, 14.25]; P = 0.17). However, the rate of AEs, including vaginal bleeding (OR: 0.10 [0.03, 0.33]; P = 0.0002), cervical canal adhesion (OR: 0.16 [0.03, 0.90]; P = 0.04), and cervical scar formation (OR: 0.04 [0.01, 0.30]; P = 0.002), was significantly lower with PDT than with conization. The degree of heterogeneity was not high. Based on our systematic review and meta-analysis, it could be concluded that PDT may be a practical approach for cervical HSIL regression compared to conization (LEEP/CKC). However, further high-quality, controlled trials are needed to confirm these findings.

Evidence for triaging HPV-positive women using viral load: data from two large cohort-screening projects in different regions of China

To evaluate the effectiveness of viral load (VL)-based triage strategies for human papillomavirus (HPV)-positive women, utilizing data from two large cohort screening studies. We analyzed 1656 HPV-positive cases identified among 25,419 screening participants. Collected data included HPV testing, cytology, and pathologically confirmed diagnoses. VL-based triage strategies were compared to a guideline-recommended cytology-based triage. The cycle threshold (Ct) value, representing HPV VL, was used for triage, with the 75th percentile of Ct values established as the cut-off. Outcomes were assessed for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+. The mean participant age was 43 ± 7.99 years. Two triage strategies were compared: (1) HPV-16/18 and other types with Ct ≤ the 75th percentile cut-off (higher viral load), and (2) HPV-16/18 & other types with cytology (referring those with ≥ atypical squamous cells of undetermined significance [ASCUS] for colposcopy). The VL-based strategy demonstrated higher sensitivity than the cytology-based strategy for detecting CIN2+ (91.52% vs. 85.27%, p = 0.016) and was comparable for detecting CIN3+ (95.60% vs. 96.70%, p = 1.000). Similarly, the strategy using HPV-16/18 with Ct ≤ 75th & other types with Ct ≤75th was also comparable to the cytology-based approach for detecting both CIN2+ (87.05% vs. 85.27%, p = 0.636) and CIN3+ (95.60% vs. 96.70%, p = 1.000). Viral load-based triage effectively identifies cervical precancer/ cancer in HPV-positive individuals without cytology, allows single-sample collection, reduces multiple visits, and may be most useful where cytology is unavailable or unreliable-acknowledging an increased colposcopy referral.