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Peer-reviewedCC BY 4.0Frontiers in Oncology

The cervicovaginal microbiome as a candidate correlate and potential predictor of HPV clearance and treatment response after HSIL therapy: a scoping review

  • Benjamin Mwesige1
  • Bridget Angucia1
  • Langanani Mbodi2
  • Absalom Mwazha3
  • Nixon Niyonzima1
  • Judith Mwansa-Kambafwile4
  • Robert F. Breiman5
  • Henry Zakumumpa6
  • Admire Chikandiwa7
7 affiliations
  1. 1Uganda Cancer Institute
  2. 2Department of Obsetrics and Gynecology Oncology Unit, University of Witwatersrand
  3. 3Discipline of Anatomical Pathology, School of Medicine, College of Health Sciences, Universitry of KwaZulu-Natal
  4. 4National Health Laboratory Services
  5. 5Department of Global Health, Rollins School of Public Health, Emory University
  6. 6School of Public Health, Makerere University
  7. 7Wits Planetary Health Research, Faculty of Health Sciences and affiliate of IDORI, University of Witwatersrand
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Abstract

Background: Persistent high-risk human papillomavirus (hrHPV) infection causes virtually all high-grade squamous intraepithelial lesions (HSIL) and cervical cancer, but only a minority progress, implicating host and microenvironmental cofactors. The cervicovaginal microbiome (CVM), particularly Lactobacillus-dominated communities, may influence hrHPV persistence, clearance, and response to HSIL treatment.

Objective: To map evidence linking the CVM with hrHPV clearance and outcomes after HSIL treatment, including loop electrosurgical excision procedure (LEEP) and conization, using PRISMA-ScR and Arksey and O’Malley frameworks.

Methods: Literature on cervicovaginal microbiota, community state types (CSTs), HPV natural history, HSIL/CIN treatment, probiotics, microbiome-directed interventions, and predictive biomarkers was systematically searched and narratively synthesized using a Population-Concept-Context framework.

Results: Sixty-six sources were charted. Lactobacillus crispatus -dominated communities (CST-I) were associated with hrHPV clearance and favorable post-treatment outcomes, whereas CST-IV, bacterial vaginosis, and increased alpha-diversity were associated with hrHPV persistence, greater HSIL severity, and treatment failure. Proposed mechanisms include lactic acid-mediated pH regulation, D-lactic acid signaling, and modulation of viral oncoproteins and immune responses. Excision altered the CVM, with restoration of Lactobacillus dominance accompanying viral clearance. Microbial-signature machine-learning models showed promising but preliminary predictive performance. Oral and intravaginal probiotics showed inconsistent but generally favorable trends, with strongest evidence for intravaginal L. crispatus transplantation. Gut microbiome diversity may also influence chemoradiotherapy outcomes in invasive cervical cancer.

Conclusion: The CVM is a promising predictor of hrHPV clearance and HSIL treatment response. However, methodological heterogeneity, small cohorts, and limited prospective evidence restrict clinical translation. Large prospective studies and rigorously designed trials are needed to validate predictive signatures and determine whether microbiome profiling or targeted modulation can improve HSIL management and outcomes.

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Cite

BibTeXRIS
BibTeX
@article{mwesige2026cervicovaginal,
  title = {{The cervicovaginal microbiome as a candidate correlate and potential predictor of HPV clearance and treatment response after HSIL therapy: a scoping review}},
  author = {Benjamin Mwesige and Bridget Angucia and Langanani Mbodi and Absalom Mwazha and Nixon Niyonzima and Judith Mwansa-Kambafwile and Robert F. Breiman and Henry Zakumumpa and Admire Chikandiwa},
  journal = {Frontiers in Oncology},
  year = {2026},
  month = oct,
  doi = {10.3389/fonc.2026.1972845},
  url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1972845/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - The cervicovaginal microbiome as a candidate correlate and potential predictor of HPV clearance and treatment response after HSIL therapy: a scoping review
AU  - Benjamin Mwesige
AU  - Bridget Angucia
AU  - Langanani Mbodi
AU  - Absalom Mwazha
AU  - Nixon Niyonzima
AU  - Judith Mwansa-Kambafwile
AU  - Robert F. Breiman
AU  - Henry Zakumumpa
AU  - Admire Chikandiwa
PY  - 2026
DA  - 2026/10/22
JO  - Frontiers in Oncology
DO  - 10.3389/fonc.2026.1972845
UR  - https://www.frontiersin.org/articles/10.3389/fonc.2026.1972845/full
AB  - Background: Persistent high-risk human papillomavirus (hrHPV) infection causes virtually all high-grade squamous intraepithelial lesions (HSIL) and cervical cancer, but only a minority progress, implicating host and microenvironmental cofactors. The cervicovaginal microbiome (CVM), particularly Lactobacillus-dominated communities, may influence hrHPV persistence, clearance, and response to HSIL treatment.  Objective: To map evidence linking the CVM with hrHPV clearance and outcomes after HSIL treatment, including loop electrosurgical excision procedure (LEEP) and conization, using PRISMA-ScR and Arksey and O’Malley frameworks.  Methods: Literature on cervicovaginal microbiota, community state types (CSTs), HPV natural history, HSIL/CIN treatment, probiotics, microbiome-directed interventions, and predictive biomarkers was systematically searched and narratively synthesized using a Population-Concept-Context framework.  Results: Sixty-six sources were charted. Lactobacillus crispatus -dominated communities (CST-I) were associated with hrHPV clearance and favorable post-treatment outcomes, whereas CST-IV, bacterial vaginosis, and increased alpha-diversity were associated with hrHPV persistence, greater HSIL severity, and treatment failure. Proposed mechanisms include lactic acid-mediated pH regulation, D-lactic acid signaling, and modulation of viral oncoproteins and immune responses. Excision altered the CVM, with restoration of Lactobacillus dominance accompanying viral clearance. Microbial-signature machine-learning models showed promising but preliminary predictive performance. Oral and intravaginal probiotics showed inconsistent but generally favorable trends, with strongest evidence for intravaginal L. crispatus transplantation. Gut microbiome diversity may also influence chemoradiotherapy outcomes in invasive cervical cancer.  Conclusion: The CVM is a promising predictor of hrHPV clearance and HSIL treatment response. However, methodological heterogeneity, small cohorts, and limited prospective evidence restrict clinical translation. Large prospective studies and rigorously designed trials are needed to validate predictive signatures and determine whether microbiome profiling or targeted modulation can improve HSIL management and outcomes.
SN  - 2234-943X
ER  -