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In this pilot longitudinal study, we investigate the potential of vaginal microbiome biomarkers to predict CIN3 development in hrHPV-positive (hrHPV+) women of reproductive age and assess loop electrosurgical excision procedure (LEEP) outcomes.<\/jats:p>\n          <jats:p>Fifty-nine non-menopausal women 20\u201353 years old, with normal cytology, were selected from the ARTISTIC trial and followed up twice over six years. Vaginal microbiome was analysed by 16S rRNA sequencing. HrHPV+ women with CIN3 showed a significant overrepresentation of <jats:italic>Sneathia amnii<\/jats:italic>, <jats:italic>Megasphaera genomosp., Peptostreptococcus anaerobius and Achromobacter spanius<\/jats:italic> (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Successfully LEEP-treated hrHPV-negative women exhibited increased <jats:italic>Lactobacillus<\/jats:italic> species, especially <jats:italic>Lactobacillus gasseri<\/jats:italic>. Additionally, <jats:italic>Lactobacillus helveticus<\/jats:italic>, <jats:italic>suntoryeus<\/jats:italic> and <jats:italic>vaginalis<\/jats:italic> showed a potential protective role against CIN3 development.<\/jats:p>\n          <jats:p>These unique microbial biomarkers associated with CIN3 development and recovery following LEEP treatment bring new insights into the vaginal microbiome\u2019s role on disease progression.<\/jats:p>","DOI":"10.1038\/s42003-025-08328-w","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T17:34:05Z","timestamp":1749231245000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A longitudinal pilot study in pre-menopausal women links cervicovaginal microbiome to CIN3 progression and recovery"],"prefix":"10.1038","volume":"8","author":[{"given":"Cristiana","family":"Banila","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4807-1292","authenticated-orcid":false,"given":"Efthymios","family":"Ladoukakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Scibior-Bentkowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro Rodrigues","family":"Santiago","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Reuter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6984-9454","authenticated-orcid":false,"given":"Michelle","family":"Kleeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8711-4577","authenticated-orcid":false,"given":"Belinda","family":"Nedjai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"8328_CR1","doi-asserted-by":"publisher","first-page":"16086","DOI":"10.1038\/nrdp.2016.86","volume":"2","author":"M Schiffman","year":"2016","unstructured":"Schiffman, M. et al. 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