Background: With the implementation of primary high-risk human papillomavirus (hrHPV) screening in the Netherlands, an increase was observed in the number of unnecessary referrals (≤Cervical Intraepithelial Neoplasia (CIN) 1) to colposcopy. We aimed to investigate which alternative triage strategies safely reduce unnecessary referrals in HPV-based cervical cancer screening programmes. Methods: Microsimulation model MISCAN was used to simulate an unvaccinated cohort of ten million 30-year old Dutch women. We calculated unnecessary referrals, cervical cancer incidence, mortality, costs and QALYs for 24 triage strategies. Condition for direct referral (atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), conditional on HPV-genotype 16/18/other high risk (OHR)), type of triage test (cytology alone or combined with hrHPV) and time to triage test (6 or 12 months) was varied. Results: The 24 triage strategies had varying effects on the number of unnecessary referrals ranging from −72% to +35%. Adjusting conditions for referral to ‘HPV16/18+ and ASC-US+’ and ‘HPVOHR+ and HSIL+’ and extending the interval between tests to 12 months resulted in a reduction in unnecessary referrals of 40% (incidence +0%, mortality −1%). Reduction in unnecessary referrals without genotyping was achieved by adjusting conditions for direct referral to LSIL (12 months to repeat test) (unnecessary referrals −37%, incidence +2%, mortality +0%). Conclusions: To reduce the number of unnecessary referrals without increasing incidence and mortality by more than 2% in the Dutch cervical cancer screening programme, genotyping for HPV16 or HPV16/18 should be implemented with 12 months to repeat testing.

Cervical cancer screening, HPV genotyping, HPV screening, Modelling study, Triage strategies,
Gynecologic Oncology
Department of Public Health

Kaljouw, S. (Sylvia), Jansen, E.E.L. (Erik E.L.), Aitken, C.A. (Clare A.), Harrijvan, L.M. (Lotte M.), Naber, S.K, & de Kok, I.M.C.M. (2021). Reducing unnecessary referrals for colposcopy in hrHPV-positive women within the Dutch cervical cancer screening programme: A modelling study. Gynecologic Oncology. doi:10.1016/j.ygyno.2020.12.038