Accuracy of Combined Molecular and Morphology-Based Triage for HPV-Positive Women in Routine Cervical Cancer Screening Services From Colombia

Abstract

Background: WHO target goals for cervical cancer elimination comprise 70% screening coverage and treatment of 90% of precancerous lesions; however, these goals are hard to achieve in real-world settings given the variability in screening and diagnostic quality and adherence. Methods: We conducted a cross-sectional study in routine screening services. HPV DNA-positive screened women underwent six triage strategies (conventional cytology, two methods of visual inspection, HPV-genotyping, telomerase, and HPV mRNA). Positive triage results underwent regular colposcopy/biopsy in public hospitals. Adjusted sensitivity, specificity, and predictive values for CIN2+/CIN3+ were estimated for stand-alone and combined tests. We explored the impact of screening units and the triage strategy on referral rates and the complete screening algorithm (screening and triage). Findings: 16,242 women underwent HPV screening and 1,789 (11·0%) were HPV-positive. In total, 20·1% of women were lost to follow-up. mRNA showed the highest positivity rate (64·1% for HPV-positive and 5·7% for the total screened cohort), the highest sensitivity (0·94) and the lowest specificity (0·36). Co-testing with mRNA had the highest improvement in sensitivity and cytology the second highest. Co-testing with HPV genotyping significantly increased the sensitivity of cytology and visual inspection (close to 0.90). Sensitivity, but not specificity, was significantly different between screening units for cytology and visual inspection. Interpretation: Morphology-based triage for HPV-positive women is a suitable alternative for routine practice in low and middle-income settings if combined with HPV-genotyping; however, point-of-care triage is preferred to reduce losses to follow-up. mRNA triage deserves cost-benefit analysis. Funding: Instituto Nacional de Cancerologia de Colombia Declaration of Interest: None to declare. Ethical Approval: The protocol was approved by the Ethical Committee at the National Cancer Institute of Colombia (INC) and informed consent was provided by every participant.