Extracellular vesicular Wnt7b mediates HPV E6-induced cervical cancer angiogenesis by activating the ß-catenin signaling pathway.

BACKGROUND: The E6 oncoproteins of human papillomavirus (HPV) 16/18 are the critical drivers of cervical cancer (CC) progression. Extracellular vesicles (EVs) are emerging as critical mediators of cancer-tumor microenvironment (TME) communication. However, whether EVs contribute to HPV 16/18 E6-mediated impacts on CC progression remains unclear. METHODS: A series of in vitro and in vivo assays were performed to elucidate the roles and mechanism of EV-Wnt7b in HPV E6-induced CC angiogenesis. The prognostic value of serum EV-Wnt7b was determined and a predictive nomogram model was established. RESULTS: HPV 16/18 E6 upregulated Wnt7b mRNA expression in four HPV 16/18-positive CC cell lines and their EVs. In vitro and in vivo experiments demonstrated that EV-Wnt7b mRNA was transferred to and modulated human umbilical vein endothelial cells (HUVECs) toward more proliferative and proangiogenic behaviors by impacting ß-catenin signaling. Clinically, serum EV-Wnt7b levels were elevated in CC patients and significantly correlated with an aggressive phenotype. Serum EV-Wnt7b was determined to be an independent prognostic factor for CC overall survival (OS) and recurrence-free survival (RFS). Notably, we successfully established a novel predictive nomogram model using serum EV-Wnt7b, which showed good prediction of 1- and 3-year OS and RFS. CONCLUSIONS: Our results illustrate a potential crosstalk between HPV 16/18-positive CC cells and HUVECs via EVs in the TME and highlight the potential of circulating EV-Wnt7b as a novel predictive biomarker for CC prognosis.

Clinical outcomes of vaginectomy and laser ablation for the treatment of post-hysterectomy women with vaginal high-grade squamous intraepithelial lesions: A retrospective study.

OBJECTIVE: To evaluate the clinical outcomes of vaginectomy and laser ablation for the treatment of vaginal high-grade squamous intraepithelial lesion (HSIL) patients who underwent previous hysterectomy for cervical HSIL or cancer. STUDY DESIGN: The clinicopathologic data and follow-up information of 167 post-hysterectomy vaginal HSIL patients who underwent laser ablation or vaginectomy were retrospectively reviewed from 2010 to 2018 at the Obstetrics and Gynecology Hospital of Fudan University. RESULTS: Of the 167 vaginal HSIL patients enrolled, 74 patients underwent vaginectomy, and 93 patients underwent laser ablation. At a median follow-up of 15 months, 13 (7.8 %) patients experienced progression to vaginal cancer, and 22 (13.2 %) patients had persistent/recurrent disease. Upon multivariate analysis, laser ablation (OR: 5.16, p = 0.02), cytology indicating HSIL (OR: 25.45, p = 0.00), and a shorter interval between previous hysterectomy and vaginal HSIL diagnosis (< 24 vs ≥ 24 months, OR: 0.10, p = 0.02) were associated with disease persistence/recurrence. In post-hysterectomy for cervical HSIL patients, the vaginectomy group had a significantly higher recurrence-free survival rate (RFS, 94.5 % vs 69.0 %, p = 0.00) and a similar progression-free survival rate (PFS, 96.4 % vs 91.4 %, p = 0.17) compared with the laser ablation group. Among post-hysterectomy for cervical cancer patients, RFS (89.5 % vs 65.7 %, p = 0.04) and PFS (100.0 % vs 82.9 %, p = 0.05) were both higher in the vaginectomy group than in the laser ablation group. CONCLUSION: Compared with laser ablation, vaginectomy resulted in better clinical outcomes among vaginal HSIL patients who had undergone previous hysterectomy for cervical neoplasia.