The association of fungal infection in cervical cancer: a systematic review and meta-analysis

BACKGROUND: Emerging evidence suggests a potential link between the fungal mycobiome and carcinogenesis. However, the relationship between fungal infection and cervical cancer progression remains inconclusive. This meta-analysis aimed to determine the pooled prevalence of fungal infection across different cervical pathological stages and assess its association with cervical lesions and HPV infection. PROSPERO CRD42024588513 is the registration number for the systematic review. METHODS: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines. We systematically searched PubMed, Web of Science, and Embase for studies published between January 1, 2004, and December 1, 2025. Observational studies (cross-sectional, case-control, cohort) with sample sizes ≥ 100 were included. Two reviewers independently performed study selection, data extraction, and quality assessment using the Newcastle-Ottawa Scale. Pooled prevalence and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models in STATA. RESULTS: Seventeen studies involving 97,382 patients with cervical lesions and 450,724 controls were included. The overall pooled prevalence of fungal infection was significantly higher in cervical cancer patients (19%, 95% CI: 0.07-0.30) compared to non-cancer patients (8%, 95% CI: 0.06-0.10). In patients with precancerous lesions (CIN1, CIN2/3), the fungal infection rate was similar to that in normal controls (NILM). Subgroup analysis among non-NILM patients revealed a higher risk of fungal infection in HPV-positive individuals than in HPV-negative individuals (OR = 1.39, 95% CI: 1.07-1.81). Meta-regression identified geographic region (Europe) as a significant source of heterogeneity. CONCLUSIONS: Fungal infection was more prevalent in invasive cervical cancer than in precancerous lesions or normal cervix, suggesting a potential association with late-stage carcinogenesis rather than early initiation. The observed association between fungal infection and HPV-positive status warrants further investigation. These findings highlight the need for prospective studies to clarify the role of the cervical mycobiome in cervical cancer progression.