Improving Efficiency in Dutch Cervical Screening by Genotyping: An Analysis of Real World Program Data

Ellen M. G. Olthof & Willem J.G. Melchers

ABSTRACT

High‐risk human papillomavirus (hrHPV)‐genotype specific risk stratification may improve cervical screening efficiency. This study evaluates the risks of cervical intraepithelial neoplasia (CIN), cancer and unnecessary referrals by hrHPV‐genotype in cytology‐positive (ASCUS+) women, using data from the Dutch population‐based cervical screening program. Data from hrHPV+/ASCUS+ women screened between January 2017 and March 2018 were analyzed using the Dutch Screening and Pathology databases. Risks for CIN2+/3+, cancer, and unnecessary referral (i.e., without CIN2+) were evaluated by hrHPV‐genotype (HPV16, HPV18, hrHPV‐other (i.e., non‐16/18 hrHPV), or mixed HPV16/18) using logistic regression, adjusted for age, laboratory (as proxy for region), sampling method (self‐ vs. clinician sampling), and stratified by age (< 50/≥ 50 years). HPV16+ women had 3.7 (CI: 3.42–3.95) and 4.6 (CI: 4.24–4.99) times higher risks of CIN2+ and CIN3+, respectively, compared to hrHPV‐other. HPV18+ women had 1.6 (CI: 1.43–1.79) and 1.9 (CI: 1.68–2.18) times higher risks. The cervical cancer risk was tenfold higher for both HPV16 (OR: 9.85, CI: 6.50–14.95) and HPV18 (OR: 10.27, CI: 6.33–16.68). Women with HPV16 had 70% and HPV18 40% lower risks of unnecessary referral, compared to hrHPV‐other. All risk differences between HPV16 or HPV18 and hrHPV‐other were statistically significant in both age groups (< 50 and ≥ 50 years). Given the significantly higher risk of CIN2+/3+ and cancer associated with HPV16 and HPV18 and the reduced likelihood of unnecessary referrals compared to hrHPV other, these findings support the use of genotype‐based colposcopy referrals in cervical screening to enhance screening efficiency.