HPV testing is more sensitive but less specific than cytology. Thus some triage is needed.
n/a
A pooled analysis of 4 RCTs showed no heterogeneity between studies in reduced invasive cancer incidence with HPV vs. cytology despite 3/4 used this approach and ¼ direct referral of all HPV+ women to colposcopy. Conversely, the biopsy rate was double in the HPV vs. cytology arm in the study that applied direct referral while there was no difference between arms in the 3 RCTs that used this triage approach. A number of biomarkers have been studied as possible triage tests, including genotyping, p16 over-expression (alone or combined with Ki67), methylation of human and viral genes and expression of the E6 viral onco-protein. A systematic review is needed.
Triage entails risk stratification. Women should be referred to colposcopy if the probability of carrying a colposcopy-detectable CIN2+ is sufficiently high (e.g. ≥10%), otherwise re-invited for new testing at an interval such that the risk of developing new cancer before it is very low. Given the long time needed for progression to invasion this mainly depends on the cross-sectional sensitivity of the triage test for CIN3. Strategies with short term HPV repeat entail high overall referral independently of the triage test. Very sensitive immediate triage (e.g. by combination of tests) can be efficient if it allows repeat after long interval, even if immediate referral is high. At the first screening with HPV long lasting lesions can be present. They have high risk of progression to cancer if missed by triage test(s). Conversely, at subsequent screens with HPV such lesions have plausibly been removed and just those recent - thus at low risk of progression to cancer - are present. In addition, for the same reason, the probability of carrying a high-grade CIN is much lower in a woman found to be HPV-positive after the first screen than in a woman with an HPV infection detected at the first screen by HPV. Thus triage can be much less aggressive at subsequent than at the first screen by HPV. Similar reasoning is true for vaccinated women.