Features of the cervicovaginal microenvironment drive cancer biomarker signatures in patients across cervical carcinogenesis
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Author
Łaniewski, PawełCui, Haiyan
Roe, Denise J
Barnes, Dominique
Goulder, Alison
Monk, Bradley J
Greenspan, David L
Chase, Dana M
Herbst-Kralovetz, Melissa M
Affiliation
Univ Arizona, Coll Med Phoenix, Dept Basic Med SciUniv Arizona, UA Canc Ctr
Univ Arizona, Coll Med Phoenix, Dept Obstet & Gynecol
Issue Date
2019-05-14
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NATURE PUBLISHING GROUPCitation
Łaniewski, P., Cui, H., Roe, D. J., Barnes, D., Goulder, A., Monk, B. J., ... & Herbst-Kralovetz, M. M. (2019). Features of the cervicovaginal microenvironment drive cancer biomarker signatures in patients across cervical carcinogenesis. Scientific reports, 9(1), 7333.Journal
SCIENTIFIC REPORTSRights
© The Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
Persistent human papillomavirus (HPV) infection is the vital factor driving cervical carcinogenesis; however, other features of the local cervicovaginal microenvironment (CVM) may play a critical role in development of precancerous cervical dysplasia and progression to invasive cervical carcinoma (ICC). 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 HPV-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 Lactobacillus 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-Lactobacillus-dominant VMB, that have been associated with HPV persistence, dysplasia and progression to ICC.Note
Open access journalISSN
2045-2322PubMed ID
31089160Version
Final published versionSponsors
Flinn Foundation [1974]; National Institutes of Health NIAID [1R15AI113457-01A1]; National Institutes of Health NCI [P30 CA023074]ae974a485f413a2113503eed53cd6c53
10.1038/s41598-019-43849-5
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