The Human Vaginal Virome: Composition, Microbiome Interactions, and Implications for Bacterial Vaginosis, HPV Persistence, and Preterm Birth
This narrative review maps vaginal virome composition and its associations with bacterial vaginosis, HPV persistence, and preterm birth, without establishing causality in any of the described relationships.
| Population | Reproductive-age women, pregnant women, and populations with bacterial vaginosis or HPV infection |
|---|---|
| Intervention | Metagenomic characterization of the vaginal/cervicovaginal virome |
| Comparator | No controlled comparator; narrative review of observational and experimental studies |
| Outcome | Vaginal virome composition and diversity; Virome-bacterial vaginosis association; Virome-HPV persistence and cervical disease association; Virome-preterm birth association; Bacteriophage-vaginal bacterial microbiome interaction; Mucosal immune modulation by the virome; Phage therapy and endolysins for bacterial vaginosis |
Summary of findings
| Outcome | Effect | 95% CI | Certainty | Clinical relevance | Notes |
|---|---|---|---|---|---|
| Vaginal virome composition and diversity | no pooled estimate; qualitative synthesis only | — | Very low | — | |
| Virome-bacterial vaginosis association | no pooled estimate; qualitative synthesis only | — | Very low | — | |
| Virome-HPV persistence and cervical disease association | no pooled estimate; qualitative synthesis only | — | Very low | — | |
| Virome-preterm birth association | no pooled estimate; qualitative synthesis only | — | Very low | — | |
| Bacteriophage-vaginal bacterial microbiome interaction | no pooled estimate; qualitative synthesis only | — | Very low | — | |
| Mucosal immune modulation by the virome | no pooled estimate; qualitative synthesis only | — | Very low | — | |
| Phage therapy and endolysins for bacterial vaginosis | investigational only; in the clinical trial data reported | — | Very low | — |
Context
The vaginal virome — bacteriophages, eukaryotic viruses, and integrated viral elements — remains substantially less characterized than the vaginal bacteriome. Recent metagenomic studies associate viromic alterations with vaginal ecological instability and mucosal inflammation. A critical synthesis of this evidence is relevant for clinicians managing bacterial vaginosis, persistent HPV, and prematurity risk.
What the study showed
Bacteriophages dominate vaginal sequencing datasets and coexist with Lactobacillus-dominated bacterial communities. Eukaryotic viruses — particularly Papillomaviridae, Anelloviridae, and Polyomaviridae — are detected in asymptomatic women. Alterations in the cervicovaginal virome are associated with genital inflammation and altered cytokine profiles, but no causal relationship has been established. No absolute numbers, 95% CIs, or effect sizes were reported, as no meta-analysis or primary quantitative analysis was performed.
How it was done
Structured narrative review with searches in PubMed/MEDLINE, Scopus, Web of Science, and Embase from database inception through August 2026. Included observational studies, longitudinal cohorts, metagenomic/viromic investigations, experimental and ex vivo studies, clinical trials, and reviews. No meta-analysis or formal risk-of-bias assessment was performed.
Effect magnitude
No aggregated effect size was calculated. Reported associations are qualitative, derived from heterogeneous primary studies without quantitative synthesis.
Risk of bias
No formal risk-of-bias tool (RoB 2, ROBINS-I, AMSTAR-2) was applied, a methodological limitation explicitly acknowledged by the authors. Substantial heterogeneity in sampling protocols, sequencing platforms, bioinformatic pipelines, and populations prevents direct comparisons across studies. The absence of reproducible viromic classifications equivalent to bacterial CSTs limits ecological interpretation.
What this study does NOT prove
This review does not prove causality between any component of the vaginal virome and bacterial vaginosis, HPV persistence, or preterm birth. It is not generalizable to populations not represented in the reviewed primary studies and does not support any virome-based therapeutic intervention.
In clinical practice
Clinicians should not modify clinical practice based on this review, as no causal evidence or validated virome-derived interventions exist. Knowledge of bacteriophages and endolysins as therapeutic strategies for Gardnerella biofilms is investigational with no immediate clinical application. Monitoring primary literature on phage therapy for recurrent bacterial vaginosis may be relevant in the medium term.
Limitations
No formal risk-of-bias tool (RoB 2, ROBINS-I, AMSTAR-2) was applied, a methodological limitation explicitly acknowledged by the authors. Substantial heterogeneity in sampling protocols, sequencing platforms, bioinformatic pipelines, and populations prevents direct comparisons across studies. The absence of reproducible viromic classifications equivalent to bacterial CSTs limits ecological interpretation.
What is still missing
Prospective longitudinal studies with standardized viromics protocols are needed to determine whether viromic alterations precede or follow transitions between vaginal eubiosis and dysbiosis. Controlled clinical trials of phage therapy and endolysins in bacterial vaginosis need to report primary clinical outcomes with adequate follow-up.
Technical appendix
Version history
- 1.0 · 2026-11-07 — Auto-generated under Evidence Standard v1.0