Recurrent cytologic inflammation on cervical smear and risk of low-grade cervical abnormalities in cytology-based screening: A 25-year multicenter cohort study from HPV-resource–limited settings
Cytologic inflammation is a common finding in cervical screening, yet its clinical significance remains uncertain, particularly in settings where human papillomavirus (HPV) testing is not routinely available. We examined whether recurrent inflammatory findings on Papanicolaou (Pap) smears predict subsequent cervical abnormalities in a cytology-based screening context. We conducted a 25-year multicenter hospital-based cohort study including 21,574 women who underwent at least three consecutive Pap smears between 1997 and 2021 at three teaching hospitals in Taiwan. The number of baseline smears showing inflammation was defined as the exposure. Subsequent cytologic outcomes (ASC-US, ASC-H, LSIL, HSIL+) and histologic outcomes (CIN1 and CIN2 +) were identified from hospital registries. Adjusted hazard ratios (HRs) were estimated using Cox proportional hazards models. Women with any cytologic inflammation had significantly higher risks of subsequent cytologic abnormalities, including ASC-US and ASC-H (HR = 1.61, 95% CI 1.27-2.04), LSIL (HR = 1.64, 95% CI 1.06-2.54), as well as histologic CIN1 (HR = 1.50, 95% CI 1.07-2.10). The risk was greatest among those with recurrent inflammation (≥2 findings), with HRs of 2.24 (95% CI 1.68-2.99) for cytologic ASC-US and ASC-H, 1.81 (95% CI 1.03-3.18) for cytologic LSIL, and 1.94 (95% CI 1.27-2.97) for histologic CIN1. No significant association was observed for cytologic HSIL+ or histologic CIN2 + . Recurrent cytologic inflammation was associated with an increased risk of low-grade but not high-grade cervical lesions. These findings suggest that repeated inflammatory cytology reflects a state of cervical epithelial instability or infection-related alteration rather than direct oncogenic progression. In cytology-dominant screening settings prior to widespread HPV DNA-based screening, inflammatory findings may provide contextual information for interpreting patterns of low-grade abnormality detection and highlight the importance of structured screening frameworks during periods of screening transition.