- Design
- Systematic review and diagnostic meta-analysis
- Population
- 7494 women across 8 studies, high-risk HPV positive
- Primary outcome
- Detection of CIN2+ and CIN3+
- Effect
- CIN2+: sensitivity 0.81 (0.73 to 0.88), specificity 0.95 (0.94 to 0.96)
This meta-analysis pooled 8 diagnostic accuracy studies, 7494 women in total, of dual-gene PAX1/JAM3 methylation testing for high-grade cervical disease.
For CIN2 or worse, pooled sensitivity was 0.81 (95% CI 0.73 to 0.88) and specificity 0.95 (0.94 to 0.96). For CIN3 or worse, sensitivity was 0.85 and specificity 0.88.
Methylation triage is attractive because it is objective and can run on the same sample as HPV testing, reducing reliance on cytology reading. But these figures come from a small number of studies, mostly from one region, and the review does not compare methylation directly with cytology or HPV 16/18 genotyping.
- Treat methylation triage as promising, not yet a replacement for cytology.
- Watch for head-to-head studies against cytology and genotyping.
- If your laboratory is evaluating it, validate locally against colposcopic histology.
- In India, where cytology capacity is limited, an objective triage test would be especially useful — but cost and validation are not yet established here.
Why it matters
An objective molecular triage could relieve the cytology bottleneck in HPV-based screening.
Don't overread it
Few studies, largely from one population, with no direct comparison with cytology.
The statistics, in plain English
A specificity of 0.95 means 5 in 100 women without CIN2+ would test positive; a sensitivity of 0.81 means about 1 in 5 with CIN2+ would be missed. Pooled accuracy from a few similar studies often looks better than performance in a new population.
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