Improving cervical screening risk stratification through extended human papillomavirus genotyping and age-specific data

Abstract

High-risk human papillomavirus (HR-HPV) screening effectively reduces cervical cancer incidence, but limited specificity leads to excessive colposcopy referrals. Extended HR-HPV genotyping improves triage by accounting for genotype-specific oncogenic risks, offering a more precise framework for patient management than traditional pooled testing. This study analysed real-world screening data from a Finnish cohort of 2368 HR-HPV-positive women (Tampere region, 2017–2019) with up to 6.5 years of follow-up. Extended genotyping was performed using the Seegene Anyplex™II HPV28 Detection assay. Genotype-specific prevalence and cumulative incidence of histology-confirmed High-grade Squamous Intraepithelial Lesions or worse (HSIL+) were assessed and stratified by reflex cytology. Among 3099 detected HR-HPV genotypes, HPV16 was most prevalent (14.3%) and carried the highest HSIL+ risk (35.7%), followed by HPV33 (24.6%) and HPV18 (20.8%). A clear risk hierarchy emerged: the lowest-risk group (HPV59/39/68/51/56/66) had an HSIL+ incidence below 4.2%. Notably, HPV16-positive women with NILM/ASC-US cytology faced a 23.9% HSIL+ risk, exceeding the 21.1% risk seen in the lowest-risk genotype group even when accompanied by LSIL+ cytology. For those with both NILM/ASC-US and the lowest-risk genotypes, HSIL+ incidence was only 3.4%. A distinct hierarchy of oncogenic risk exists within this population-based cohort. Incorporating genotype-specific data into national screening algorithms is strongly supported. This allows for immediate colposcopy for high-risk groups (e.g. HPV16 with mild cytology) while justifying extended follow-up for lower-risk types, optimizing clinical resources and reducing unnecessary procedures.