Associations among HPV persistence, the vaginal microbiome, and cervical cancer recurrence

Abstract Background In the US, up to 60% of cervical cancer (CxCa) survivors will have persistent HPV infection, the causative agent of CxCa, and up to 35% will develop recurrent local CxCa within 4 years after chemo-radiation therapy. Preliminary studies suggest healthy vaginal microbiome (VM) coul...

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Main Authors: Despina Tsementzi, Rebecca Meador, Tony Eng, Joseph Shelton, Isabelle Scott, Konstantinos T. Konstantinidis, Susan Modesitt, Deborah Watkins Bruner
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Journal of Translational Medicine
Online Access:https://doi.org/10.1186/s12967-025-06811-w
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author Despina Tsementzi
Rebecca Meador
Tony Eng
Joseph Shelton
Isabelle Scott
Konstantinos T. Konstantinidis
Susan Modesitt
Deborah Watkins Bruner
author_facet Despina Tsementzi
Rebecca Meador
Tony Eng
Joseph Shelton
Isabelle Scott
Konstantinos T. Konstantinidis
Susan Modesitt
Deborah Watkins Bruner
author_sort Despina Tsementzi
collection DOAJ
description Abstract Background In the US, up to 60% of cervical cancer (CxCa) survivors will have persistent HPV infection, the causative agent of CxCa, and up to 35% will develop recurrent local CxCa within 4 years after chemo-radiation therapy. Preliminary studies suggest healthy vaginal microbiome (VM) could affect the acquisition, persistence, and clearance of HPV. Through longitudinal studies, we investigate associations between the dynamics of VM, HPV persistence, cancer recurrence (CR), and outcomes in gynecologic cancer survivors who completed cancer treatments. Methods We enrolled 49 patients with Stage IB-IIIC CxCa who completed radiation therapy (RT) alone or concurrent chemoradiation (chemoRT). VM sequencing and HPV typing were performed on samples obtained at baseline (T0, pre-treatment), T1, T2, and T3 (3, 6, and 12 months after the completion of cancer treatment). Patients were evaluated for CR up to 4 years following the end of treatment. Results Among all patients, 33% (16/49) had CxCa recurrence within 2–3 years post-therapy. The vaginal microbiome exhibited high diversity, Prevotella-dominant communities; only 20% were dominated by lactobacilli at any time. Post-treatment hrHPV was detected in 17 out of 41 women (41.5%) with follow-up samples. We identified key taxa, such as Prevotella species, which were highly associated with CxCa recurrence and post-treatment detection of hrHPV. Conclusions Our findings link Prevotella-dominant, high diversity vaginal microbiome communities with post-therapy hrHPV persistence and cervical cancer recurrence in gynecologic cancer survivors. Such findings warrant further research into the role of the microbiome in modulating cervical cancer progression and response to therapy, suggesting modulation of the microbiome with probiotics or other methods could be considered a novel approach to improve cervical cancer treatment outcomes.
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spelling doaj-art-2408d79df4e34c8fa1a3fb5e936e8d412025-08-20T03:46:24ZengBMCJournal of Translational Medicine1479-58762025-08-0123111010.1186/s12967-025-06811-wAssociations among HPV persistence, the vaginal microbiome, and cervical cancer recurrenceDespina Tsementzi0Rebecca Meador1Tony Eng2Joseph Shelton3Isabelle Scott4Konstantinos T. Konstantinidis5Susan Modesitt6Deborah Watkins Bruner7Nell Hodgson Woodruff School of Nursing, Emory UniversityNell Hodgson Woodruff School of Nursing, Emory UniversityRadiation Oncology, Winship Cancer Institute, Emory UniversityRadiation Oncology, Winship Cancer Institute, Emory UniversityGrady Memorial HospitalSchool of Civil & Environmental Engineering, Georgia Institute of TechnologyGynecologic Oncology Division, Gynecology and Obstetrics Department, School of Medicine, Emory UniversityNell Hodgson Woodruff School of Nursing, Emory UniversityAbstract Background In the US, up to 60% of cervical cancer (CxCa) survivors will have persistent HPV infection, the causative agent of CxCa, and up to 35% will develop recurrent local CxCa within 4 years after chemo-radiation therapy. Preliminary studies suggest healthy vaginal microbiome (VM) could affect the acquisition, persistence, and clearance of HPV. Through longitudinal studies, we investigate associations between the dynamics of VM, HPV persistence, cancer recurrence (CR), and outcomes in gynecologic cancer survivors who completed cancer treatments. Methods We enrolled 49 patients with Stage IB-IIIC CxCa who completed radiation therapy (RT) alone or concurrent chemoradiation (chemoRT). VM sequencing and HPV typing were performed on samples obtained at baseline (T0, pre-treatment), T1, T2, and T3 (3, 6, and 12 months after the completion of cancer treatment). Patients were evaluated for CR up to 4 years following the end of treatment. Results Among all patients, 33% (16/49) had CxCa recurrence within 2–3 years post-therapy. The vaginal microbiome exhibited high diversity, Prevotella-dominant communities; only 20% were dominated by lactobacilli at any time. Post-treatment hrHPV was detected in 17 out of 41 women (41.5%) with follow-up samples. We identified key taxa, such as Prevotella species, which were highly associated with CxCa recurrence and post-treatment detection of hrHPV. Conclusions Our findings link Prevotella-dominant, high diversity vaginal microbiome communities with post-therapy hrHPV persistence and cervical cancer recurrence in gynecologic cancer survivors. Such findings warrant further research into the role of the microbiome in modulating cervical cancer progression and response to therapy, suggesting modulation of the microbiome with probiotics or other methods could be considered a novel approach to improve cervical cancer treatment outcomes.https://doi.org/10.1186/s12967-025-06811-w
spellingShingle Despina Tsementzi
Rebecca Meador
Tony Eng
Joseph Shelton
Isabelle Scott
Konstantinos T. Konstantinidis
Susan Modesitt
Deborah Watkins Bruner
Associations among HPV persistence, the vaginal microbiome, and cervical cancer recurrence
Journal of Translational Medicine
title Associations among HPV persistence, the vaginal microbiome, and cervical cancer recurrence
title_full Associations among HPV persistence, the vaginal microbiome, and cervical cancer recurrence
title_fullStr Associations among HPV persistence, the vaginal microbiome, and cervical cancer recurrence
title_full_unstemmed Associations among HPV persistence, the vaginal microbiome, and cervical cancer recurrence
title_short Associations among HPV persistence, the vaginal microbiome, and cervical cancer recurrence
title_sort associations among hpv persistence the vaginal microbiome and cervical cancer recurrence
url https://doi.org/10.1186/s12967-025-06811-w
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