Reflex cytology for triage of high-risk human papillomavirus positive self-sampled material in cervical cancer screening: a prospective cohort study.

Abstract

High-risk human papillomavirus (HrHPV)-positive women detected by self-sampling require an extra visit at the general practitioner for additional cytology testing, but the loss to follow up within this triage is substantial. The aim of this study was to evaluate the clinical utility of reflex cytology on hrHPV-positive self-samples for immediate stratification of women who need referral for colposcopy. A prospective cohort study. Two Dutch cervical cancer-screening laboratories. 1014 screenees who tested hrHPV-positive on self-samples between 1 December 2018 and 1 August 2019. Self-samples were directly used for cytological analysis. Cytological and histological outcomes during follow up were obtained from the Dutch Pathology Registry (PALGA). Test performance of reflex cytology on self-samples was determined for different thresholds and compared with physician-taken cytology and histological outcomes. Reflex cytology on self-samples for detecting abnormal cytology showed a sensitivity of 26.4% (95% CI 21.8-31.3) and specificity of 90.5% (95% CI 87.7-92.8). Of all ≥CIN2 cases, 29.4% (95% CI 22.5-37.1) were detected with reflex cytology on self-samples. The positive predictive value for detection of ≥CIN2 was higher with cytology on self-collected samples than on physician-collected samples. Of women who were lost to follow up, 12.9% were found to have abnormal cytology on their self-sampled material. Cytology testing is achievable on hrHPV-positive self-samples, could decrease the loss to follow up in screening and is easily implementable in the current clinical practice. Of all hrHPV-positive women with abnormal cytology on additional physician-collected samples, 26.4% could have been directly referred for colposcopy if triage with reflex cytology on self-sampled material had been performed. Reflex cytology for triage of hrHPV⁺ self-samples is of added value for direct referral of women for colposcopy.