**5. Conclusions**

The risk of high-grade VAIN should not be underestimated in women with a history of current or former smoking and previous hysterectomy for CIN2+, which also represents a risk factor for recurrence and progression to vaginal cancer. Colposcopic findings, including grade 2, papillary and vascular patterns, are predictive factors for VAIN3 with or without stromal microinvasion. Accurate colposcopic and histologic diagnosis is crucial for the optimal management of vaginal pre-cancers and cancers. In addition, HPV genotyping could be a helpful tool for risk stratification and prompt identification of women with VAIN3 at higher risk of persistence, progression and recurrence.

**Supplementary Materials:** The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/diagnostics13020176/s1, Table S1: Patients' colposcopic features summary statisticsa by VAIN grade at diagnosis; Table S2: Missing data distribution by VAIN grade at diagnosis; Table S3: Colposcopic Grade association with Lesion type and Vascularity.

**Author Contributions:** Conceptualization, A.D.I., M.E.G., N.S. and E.P.P.; Methodology, A.D.I., D.R., M.E.G. and B.G.; Software, A.D.I., D.R. and B.G.; Validation, A.D.I. and D.R.; Formal Analysis, D.R. and S.B.; Investigation, A.D.I., M.E.G., N.S., F.B., S.M., A.M.V.U. and E.P.P.; Resources, A.D.I., M.E.G. and I.P.; Data Curation, A.D.I., D.R. and S.B.; Writing—Original Draft Preparation, A.D.I. and D.R.; Writing—Review and Editing, A.D.I., M.E.G., N.S., S.M., A.M.V.U., I.P., D.F. and E.P.P.; Visualization, A.D.I., D.R., N.S. and E.P.P.; Supervision, F.B. and D.F.; Project Administration, A.D.I. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board of the European Institute of Oncology, Milan, Italy (IEO protocol number UID 3821, date of approval: 27 October 2022).

**Informed Consent Statement:** Informed consent was obtained from all subjects involved in the study.

**Data Availability Statement:** The data presented in this study are available on request from the corresponding author. The data are not publicly available due to patients' privacy restrictions. The data are safely stored in a private database of the European Institute of Oncology, Milan, Italy.

**Acknowledgments:** This work was partially supported by the Italian Ministry of Health with Ricerca Corrente and 5x1000 funds.

**Conflicts of Interest:** The authors declare no conflict of interest. None of the authors received financial support or funding for this work.
