Extended HPV Genotyping for Risk Stratification in Cervical Screening: A Population-based Study

Population-based data on extended HPV genotyping for risk stratification in routine cervical cancer screening are limited. We evaluated the association between oncogenic risk categories derived from extended HPV genotyping and cervical screening outcomes (cytology and histology) in a large population-based cohort (October 2021-September 2023).

This retrospective observational study analyzed HPV results and corresponding cytology and histology from screened women between October 2021 and September 2023. High-risk HPV genotypes were classified into three mutually exclusive categories: high (HOT), moderate (MOT), and low (LOT), developed for the organizational framework of this particular study. Cytologic and histologic outcomes were compared across categories using chi-square tests, and PPVs for CIN2+ and CIN3+ were calculated.

Among 448,394 screened women, overall HPV prevalence was 8.6%. HOT, MOT, and LOT genotypes accounted for 35.5%, 24.0%, and 40.5% of HPV-positive infections, respectively. Cytologic severity differed significantly across oncogenic risk categories (p<.0001), with HOT genotypes contributing disproportionately to high-grade cytologic abnormalities. Histologic follow-up demonstrated marked differences in disease severity, with HOT genotypes accounting for 68.8% of CIN3+ diagnoses compared with 19.7% for MOT and 11.5% for LOT. Genotype-specific PPVs were highest for HPV16 and HPV31; category-level CIN3+ PPV was 23.0% for HOT, 14.6% for MOT, and 5.5% for LOT.

Extended HPV genotyping was associated with a clear gradient of oncogenic risk; women with low-oncogenic risk infections demonstrated markedly lower rates of high-grade disease, supporting risk-stratified clinical management in cervical cancer screening programs.