The Improving Risk Informed HPV Screening (IRIS) Study: Design and Baseline Characteristics.

Background: Cervical cancer screening with high-risk HPV (HrHPV) testing is being introduced. Most HrHPV infections are transient, requiring triage tests to identify individuals at highest risk for progression to cervical cancer. Head-to-head comparisons of available strategies for screening and triage are needed. Endometrial and ovarian cancers could be amenable to similar testing. Methods: Between 2016-2021 discard cervical cancer screening specimens from women ages 25-65 undergoing screening at Kaiser Permanente Northern California were collected. Specimens were aliquoted, stabilized, and stored frozen. HPV, cytology and histopathology results as well as demographic and co-factor information were obtained from electronic medical records. Follow-up collection of specimens was conducted for 2 years and EMR-based data collection was planned five years. Results: Collection of enrollment and follow-up specimens are complet and EMR-based follow-up data collection is ongoing. At baseline, specimens were collected from 54,971 HPV-positive, 10,219 HPV-negative/Pap-positive and 12,751 HPV-negative/Pap-negative women. Clinical history prior to baseline was available for 72.6% of individuals, of which 53.9% were undergoing routine screening, 8.6% recently had an abnormal screen, 30.3% had previous colposcopy, and 7.2% had previous treatment. As of November 2020, 55.6% had one or more colposcopies, yielding 5,515 CIN2, 2,735 CIN3 and 147 cancer histopathology diagnoses. Conclusions: This robust population-based cohort study represents all stages of cervical cancer screening, management, and post-treatment follow-up. Impact: The IRIS study is a unique and highly relevant resource allowing for natural history studies and rigorous evaluation of candidate HrHPV screening and triage markers, while permitting studies of biomarkers associated with other gynecological cancers.