Cytology and hrHPV Testing in HPV ‐Vaccinated Women Entering Cervical Screening: A Prospective Observational Study

Abstract

Objective To compare the predictive performance of cytology and high‐risk HPV (hrHPV) testing in young HPV‐vaccinated women participating in the cervical screening programme in Scotland. Design Prospective observational study. Setting Routine cervical screening services in three Scottish Health Boards between 2011 and 2015. Population Women born between 1991 and 1995 attending routine cervical screening who were eligible for HPV immunisation, including catch‐up vaccination cohorts. Methods Residual liquid‐based cytology samples were tested for hrHPV using Hybrid Capture 2. Women with high‐grade cytology, hrHPV‐positive and BNA/mild dyskaryosis, and a subset of hrHPV‐positive women with negative cytology from one participating region were invited for colposcopy. Colposcopy and histology outcomes were obtained from the National Colposcopy Clinical Information Audit System (NCCIAS). Positive and negative predictive values (PPV, NPV) for CIN2+ were estimated within the study referral framework, and hrHPV persistence across repeat testing was examined. Main Outcome Measures PPV and NPV for CIN2+ within the colposcopy referral pathway and patterns of hrHPV persistence in a selected group who attended for colposcopy. Results From 10 000 co‐tested residual samples, hrHPV positivity was 86% in borderline/mild cytology and 27% in cytology‐negative samples. Among 1352 women who attended for colposcopy, 184 CIN2+ cases were identified. Within the selective referral framework, hrHPV testing demonstrated a PPV for CIN2+ of 14.3% (95% CI: 12.5–16.4) and an NPV of 98.9% (95% CI: 94.0–99.9), while high‐grade cytology demonstrated a PPV of 71.7% (95% CI: 59.2–81.5) and an NPV of 89.2% (95% CI: 87.4–90.8). Among 1007 women with repeat testing, hrHPV persistence declined with increasing inter‐test intervals, with greater clearance observed over longer follow‐up periods. Conclusions In this early HPV‐vaccinated cohort screened within the historical Scottish programme from age 20 years, hrHPV testing retained a high negative predictive value but a low positive predictive value for CIN2+, reflecting the low prevalence of disease in vaccinated populations. These estimates reflect outcomes within a selective colposcopy referral framework and should not be interpreted as population‐level screening accuracy measures. The findings support the role of cytology triage alongside hrHPV testing while highlighting the need for further evaluation of screening strategies in highly vaccinated populations.