Risk-Stratified versus Cytology-Based Triage of Non-HPV 16/18-Positive for Detection of High-Grade Cervical...

Human papillomavirus (HPV)-based screening is increasingly being adopted as the primary strategy for cervical cancer prevention due to its superior sensitivity compared with cytology. However, effective triage of women who test positive for high-risk HPV (hrHPV), particularly those infected with non-HPV16/18 genotypes, remains a significant challenge in low-resource settings. Cytology-based triage requires substantial laboratory infrastructure and technical expertise, which may limit its scalability. Risk-stratified triage approaches incorporating readily available clinical and demographic factors may offer a practical alternative for identifying women at highest risk of cervical precancer while reducing unnecessary referrals.

The "STRAT-CIN Trial" aims to determine whether a risk-stratified triage algorithm is non-inferior to standard cytology-based triage for the detection of high-grade cervical intraepithelial neoplasia (CIN2+) among women positive for non-HPV16/18 high-risk HPV types.

This protocol describes a two-arm, parallel, open-label, non-inferiority randomized controlled trial involving sexually active women aged 30-65 years who test positive for non-HPV16/18 high-risk HPV types during routine cervical cancer screening at the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria, between June 2026 and January 2027. A total of 148 eligible women will be randomized in a 1:1 ratio to either a risk-stratified triage arm or a cytology-based triage arm. Participants in the intervention arm will be triaged using a composite algorithm incorporating age, HIV status, cigarette smoking, long-term oral contraceptive use, and multiple hrHPV genotype infections, while participants in the control arm will undergo reflex cytology according to the Bethesda 2014 classification. The primary outcome is the proportion of histologically confirmed CIN2 + lesions detected in each study arm. Secondary outcomes include diagnostic performance metrics, referral rates for colposcopy, colposcopic yield, and predictors of CIN2+. Analyses will follow the intention-to-treat principle. Differences in CIN2 + detection rates will be assessed using risk differences and corresponding 95% confidence intervals. Non-inferiority will be concluded if the lower bound of the confidence interval exceeds the pre-specified non-inferiority margin of - 10%. Logistic regression analyses will be used to identify independent predictors of CIN2+, and statistical significance will be set at P < 0.05.

The "STRAT-CIN Trial" will evaluate whether a simplified risk-stratified triage approach can achieve diagnostic performance comparable to conventional cytology-based triage among women with non-HPV16/18 high-risk HPV infections. By integrating easily obtainable clinical and demographic risk factors into triage decision-making, this study has the potential to reduce unnecessary colposcopy referrals, improve screening efficiency, and support the implementation of context-appropriate cervical cancer prevention strategies in resource-constrained settings. The findings will contribute important evidence toward optimizing HPV-based cervical cancer screening programs in Nigeria and other low-and middle-income countries.

: PACTR202606895128487 (2nd June 2026).