Human papillomavirus viral load as promising surrogate biomarker of cervical cancer risk and clinical outcome

INTRODUCTION: Cervical precancerous lesions and cancer are caused by persistent oncogenic high-risk human papillomavirus (HR-HPV). Molecular HPV DNA testing has recently replaced cytology as the preferred primary screening method because of its superior sensitivity and negative predictive value. Nevertheless, its limited specificity can result in unnecessary follow-up procedures. Therefore, the identification of surrogate biomarkers capable of distinguishing transient infections from persistent and clinically relevant ones is essential for improving triage and risk stratification. To summarize the available evidence, a comprehensive literature search was performed across PubMed/MEDLINE, Embase, Scopus, and Web of Science databases up to December 2025, identifying studies that evaluated HR-HPV viral load in relation to cervical intraepithelial lesions and cancer progression. AREAS COVERED: Oncogenic HPV viral load, defined as the quantity of HPV genomes in a cervical sample or biopsy tissue, may constitute an attractive biomarker for the progression of HPV-related cervical lesions. Indeed, HPV viral load levels are positively correlated with the persistence of cervical HR-HPV, leading to an increased risk of high-grade lesions and invasive cervical cancer. Furthermore, cervical HPV viral load quantification provides useful prognostic information regarding disease severity, therapeutic response, and recurrence following treatment of cervical lesions. EXPERT OPINION: The recent standardization and validation of available multiplex real-time PCR techniques for HPV detection and quantification supports the clinical integration of HPV viral load as a surrogate biomarker. Incorporating viral load assessment into cervical screening and management algorithms could significantly enhance diagnostic precision, enable more personalized follow-up, and guide therapeutic decisions for women affected by HR-HPV-associated precancerous and cancerous cervical diseases.