Post-Treatment High-Risk HPV Testing as a "Test of Cure": A Systematic Review

Background/Objectives: Excisional treatment is effective for cervical intraepithelial neoplasia grade 2 or 3 (CIN2-3), but residual or recurrent high-grade disease remains clinically important. This focused systematic review evaluated post-treatment high-risk human papillomavirus (hrHPV) testing as a test of cure and compared it with cytology and resection-margin status. Methods: PubMed/MEDLINE was searched and supplemented by structured citation checking and targeted verification, with supplementary Embase and CENTRAL searches conducted during peer review; the review was not prospectively registered. Mixed-grade cohorts were retained only when a high-grade subgroup was extractable or for supportive qualitative evidence. Results: Fifteen primary studies enrolled 21,932 treated women, of whom 18,992 contributed to endpoint-specific analyses. Explicit CIN2+/CIN3+/HSIL+ event rates were 1.9-6.8% in most studies, with 11.8% in one earlier intensively verified cohort; higher rates in other reports reflected any-grade CIN or composite outcomes and were not treated as CIN2+. In the subset reporting directly comparable accuracy measures, hrHPV testing was generally more sensitive than cytology and negative predictive values were 98.0-100%. These values require caution because recurrence prevalence was low and histological verification was incomplete in several cohorts. Five studies were judged at low, eight at unclear, and two at high overall risk of bias for their diagnostic-accuracy contributions. Conclusions: The evidence supports hrHPV-based risk stratification and reduced-intensity surveillance after a negative test, but not unqualified return to routine population screening. Standardised prospective studies with uniform CIN2+ endpoints and complete verification remain needed.