# Mapping the Vaginal Metabolic Profile in Dysbiosis, Persistent Human Papillomavirus Infection, and Cervical Intraepithelial Neoplasia: A Scoping Review

## TL;DR

This review maps metabolic changes in the vaginal environment linked to HPV infection and cervical dysplasia, identifying potential biomarkers for early cervical cancer detection.

## Contribution

The study systematically identifies and evaluates metabolic and protein biomarkers associated with persistent HPV infection and cervical dysplasia.

## Key findings

- HPV infection is linked to a dysbiotic vaginal environment with anaerobic bacteria like Gardnerella vaginalis.
- Prolineaminopeptidase, 5′-O-methylmelledonal, and calonectin show high diagnostic performance (AUC > 0.90).
- Vaginal microbiome and metabolic profiles may serve as promising biomarkers for persistent HPV infection.

## Abstract

Background/Objectives: This scoping review aimed to map evidence on metabolic alterations in the vaginal environment associated with dysbiosis, transient and persistent human papillomavirus (HPV) infection, and cervical dysplasia, highlighting potential metabolic and protein biomarkers for early detection of cervical cancer. Methods: Systematic searches were conducted in PubMed, Scopus, and Web of Science, following the JBI methodology and PRISMA-ScR guidelines. Studies jointly evaluating vaginal metabolites and proteins in women with HPV and cervical intraepithelial neoplasia (CIN) in the context of dysbiosis were included. Results: After duplicate removal, 196 records were screened, and 41 studies were selected—mostly cross-sectional observational designs—published between 2006 and 2025, predominantly by Chinese research groups. Lactobacillus spp. predominated in HPV-negative women, while HPV infection was associated with a dysbiotic environment enriched with anaerobes such as Gardnerella vaginalis, Atopobium vaginae, Prevotella, and Sneathia. Of 389 metabolic and protein markers associated with HPV infection and CIN, 44 underwent ROC analysis, with prolineaminopeptidase, 5′-O-methylmelledonal, and calonectin showing high diagnostic performance (AUC > 0.90). Conclusions: These results suggest vaginal microbiome and metabolic profiles may represent promising biomarkers for persistent HPV infection. Further, longitudinal studies with larger samples are needed for clinical validation.