<scp>MicroRNAs</scp> in <scp>HPV</scp> ‐Associated Carcinogenesis: Potential Biomarkers in Oropharyngeal and Cervical Cancers

Abstract

High-risk human papillomavirus (HPV) infection is a key etiological factor in cervical cancer (CC) and oropharyngeal squamous cell carcinoma (OPSCC). Increasing evidence indicates that host microRNAs (miRNAs) are central regulators in HPV-induced carcinogenesis and represent promising molecular biomarkers for diagnosis and prognosis. In cervical cancer, deregulated expressions of miRNAs such as miR-21, miR-27a, miR-34a, miR-155, and miR-218 have been consistently reported. These miRNAs influence critical pathways controlling apoptosis, cell proliferation, and immune evasion. The oncoproteins E6 and E7 from HPV can disrupt normal miRNA biogenesis, leading to the suppression of tumor-suppressor genes such as PTEN and PDCD4 and the activation of oncogenic signaling networks. Circulating miRNAs detected in serum and plasma, including miR-205 and miR-196a, show potential as non-invasive biomarkers for early detection and disease monitoring in cervical cancer (CC). In oropharyngeal cancer (OPC), particularly HPV-positive OPSCC, altered miRNAs such as miR-21, miR-31, miR-375, and miR-9 have been implicated in tumor initiation and progression. Distinct miRNA profiles have been observed between HPV-positive and HPV-negative tumors, suggesting a role for these molecules in differentiating subtypes with different clinical outcomes. Salivary and serum miRNA assays have shown potential for early detection, reflecting tumor-specific molecular changes in a minimally invasive manner. Overall, miRNA profiling offers a promising approach for stratifying HPV-associated cervical and OPCs. Integrating miRNA panels with HPV genotyping and epigenetic data may enhance precision in risk assessment and therapeutic targeting. Future longitudinal studies with standardized methodologies are needed to validate these miRNAs as reliable clinical biomarkers.