ArticleInfectious agents and cancer2026
Molecular characterization of HPV integrations in high-risk HPV-positive women and development of a prognostic signature based on integration-associated genes for cervical cancer.
Article in Infectious agents and cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundHPV integration into the human genome is a key molecular event in the progression of cervical cancer carcinogenesis.
methodsThis study utilized samples from high-risk HPV-positive women to investigate HPV integration. Integration-associated genes were screened based on HPV-DNA integration sequencing data from our local clinical cohort, and their expression levels and prognostic value were independently validated and used for model construction in the TCGA-CESC RNA-seq dataset. Using this integration-associated prognostic risk model, cervical cancer (CC) patients from TCGA were stratified into high-risk and low-risk groups. Differences in enrichment of PI3K-AKT pathway genes and immunotherapy response were analyzed between the two groups, and functional analysis was performed on differentially expressed immune-related genes between the subgroups.
resultsThe HPV integration rate gradually increases with the progression of cervical disease. The most frequent integration-related genes were KLF5, LINC00392, BCL11B and TP63. A risk model based on eight HPV integration-associated genes was developed, which could classify CC samples into high-risk groups with significantly shorter overall survival times compared to low-risk groups (P < 0.001). ROC curve evaluation showed that the AUCs for the 3, 5, and 7-year survival rates were 0.77, 0.74, and 0.76, respectively. The significant differences in PI3K-AKT pathway gene enrichment and prediction of immune therapy response were found between two risk groups.
conclusionA integration-associated prognostic risk model based on genes derived from HPV integration hotspots shows significant association with patient survival and is correlated with distinct tumor microenvironment features, including PI3K-AKT pathway activity and predicted immunotherapy response.
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