Integrating non-coding RNA profiling with HPV genotyping for cervical cancer risk stratification and early detection.

Cervical cancer is a major global health concern and a leading cause of cancer-related deaths among women worldwide. Although current diagnostic methods have improved diagnosis but are limited in distinguishing transient infections from those progressing toward malignancy. This limitation highlights the need for more precise diagnostic approaches that can support early intervention, risk assessment, and informed clinical decision-making. HPV genotyping includes identification of specific high-risk viral strains, providing essential information for infection risk assessment, disease surveillance, and vaccine evaluation. However, it does not indicate viral oncogenic activity or cellular transformation. On the other hand, ncRNAs such as miRNAs, lncRNAs, and circRNAs serve as key regulatory molecules in HPV-mediated carcinogenesis. Moreover, their stability in biological fluids supports their use as non-invasive, liquid biopsy-based diagnostics. This narrative review explores the potential of integrating HPV genotyping with ncRNA profiling as a multi-omics diagnostic approach for cervical cancer risk stratification. By combining information on viral genotype with host molecular responses, this integrated strategy may improve diagnostic accuracy, enhance patient risk stratification, and facilitate more personalized screening and management. Although individual ncRNA biomarkers have shown promising associations with HPV-associated cervical carcinogenesis, evidence supporting their combined clinical application with HPV genotyping remains limited and requires further prospective validation. Nevertheless, the integration of viral and host molecular biomarkers represents a potentially useful approach for improving molecular risk assessment and supporting the development of more personalized cervical cancer screening strategies.