Triage options to manage high-risk human papillomavirus-positive women: A population-based cross-sectional study from rural China

Improvement in managing HPV-positive women is urgently needed. Based on a population-based study which included 2112 women aged 49 to 69 from Shanxi, China, we aimed to evaluate the clinical performance of multiple triage strategies based on liquid-based cytology (LBC), p16^INK4a, viral load and partial genotyping, as a single or combined strategy for detecting cervical intraepithelial neoplasia grade 2/3 or higher (CIN2+/CIN3+) in women who tested positive by Hybrid Capture 2 (HC2). Among 452 HC2-positive women, the test positivity of LBC (ASC-US+), p16^INK4a, HPV16/18 and HPV16/18/31/33/45 were 39.6%, 38.5%, 18.0% and 40.0%, respectively. Compared to LBC (ASC-US+) triage, a single triage strategies using p16^INK4a or extended genotyping (SureX HPV16/18/31/33/45) achieved comparable sensitivity (relative sensitivity: 1.08, 95% confidence interval CI]: 0.93-1.26 and 0.96, 95% CI: 0.76-1.22) and specificity (relative specificity: 1.05, 95% CI: 0.96-1.14 and 1.02, 95% CI: 0.92-1.14) for CIN3+. Viral load triage using a ≥50 RLU/CO cut-point also yielded similar results with LBC (ASC-US+). Among combined triage strategies, HPV16/18 genotyping with reflex p16^INK4a showed higher sensitivity and slightly lower specificity than LBC (ASC-US+) for CIN3+ detection, however, the differences were not statistically significant. Of note, after a negative result by p16^INK4a or LBC among HPV16/18 negative women, the posttest probability of CIN3+ was lower than 1%. Our study suggested that p16^INK4a, extended genotyping and increased viral load cut-point could be promising alternatives to cytology triage. Combined triage algorithms of HPV16/18 with reflex p16^INK4a or cytology, if negative, are associated with the substantial low posttest risk sufficient to release women to next screening round.