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Here we investigated relationships between locally secreted cancer biomarkers and features of the local CVM to better understand the complex interplay between host, virus and vaginal microbiota (VMB). We enrolled women with ICC, high- and low-grade squamous intraepithelial lesions, as well as, HPV-positive and healthy\u00a0HPV-negative controls. A broad range of cancer biomarkers was present in the local CVM and specifically elevated in ICC patients. The majority of cancer biomarkers were positively correlated to other biomarkers and linked to genital inflammation. Several cancer biomarkers were also negatively correlated to <jats:italic>Lactobacillus<\/jats:italic> abundance and positively correlated with abnormal vaginal pH. Finally, a hierarchical clustering analysis of cancer biomarkers and immune mediators revealed three patient clusters, which varied in levels of cancer biomarkers, genital inflammation, vaginal pH and VMB composition. Specific cancer biomarkers discriminated patients with features of the CVM, such as high genital inflammation, elevated vaginal pH and dysbiotic non-<jats:italic>Lactobacillus<\/jats:italic>-dominant VMB, that have been associated with HPV persistence, dysplasia and progression to ICC.<\/jats:p>","DOI":"10.1038\/s41598-019-43849-5","type":"journal-article","created":{"date-parts":[[2019,5,14]],"date-time":"2019-05-14T10:04:05Z","timestamp":1557828245000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":91,"title":["Features of the cervicovaginal microenvironment drive cancer biomarker signatures in patients across cervical carcinogenesis"],"prefix":"10.1038","volume":"9","author":[{"given":"Pawe\u0142","family":"\u0141aniewski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise J.","family":"Roe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Goulder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley J.","family":"Monk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Greenspan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana M.","family":"Chase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8540-5917","authenticated-orcid":false,"given":"Melissa M.","family":"Herbst-Kralovetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,5,14]]},"reference":[{"key":"43849_CR1","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1097\/OLQ.0b013e318285c6d2","volume":"40","author":"K Owusu-Edusei Jr.","year":"2013","unstructured":"Owusu-Edusei, K. Jr. et al. The estimated direct medical cost of selected sexually transmitted infections in the United States, 2008. Sex Transm Dis 40, 197\u2013201, https:\/\/doi.org\/10.1097\/OLQ.0b013e318285c6d2 (2013).","journal-title":"Sex Transm Dis"},{"key":"43849_CR2","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.virol.2010.02.002","volume":"401","author":"HU Bernard","year":"2010","unstructured":"Bernard, H. U. et al. Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments. Virology 401, 70\u201379, https:\/\/doi.org\/10.1016\/j.virol.2010.02.002 (2010).","journal-title":"Virology"},{"key":"43849_CR3","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1001\/jamaoncol.2016.5688","volume":"3","author":"Global Burden of Disease Cancer Collaboration","year":"2017","unstructured":"Global Burden of Disease Cancer Collaboration. et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncol 3, 524\u2013548, https:\/\/doi.org\/10.1001\/jamaoncol.2016.5688 (2017).","journal-title":"JAMA Oncol"},{"key":"43849_CR4","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1002\/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F","volume":"189","author":"JM Walboomers","year":"1999","unstructured":"Walboomers, J. M. et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189, 12\u201319, https:\/\/doi.org\/10.1002\/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F (1999).","journal-title":"J Pathol"},{"key":"43849_CR5","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1093\/jnci\/87.18.1365","volume":"87","author":"GY Ho","year":"1995","unstructured":"Ho, G. 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