As is well known, HPV testing is sensitive but not very specific for high-grade Cervical Intraepithelial neoplasia (CIN) whereas high-grade cytology is specific but not very sensitive. By using the more sensitive HPV test as the primary screen and triaging with the more specific test (cytology) one should be able to maintain much of the added sensitivity of HPV testing without referring too many additional women to colposcopy. Ideally triage would divide screen positive women into two groups those who should be referred immediately to colposcopy and those who can be discharged back to routine screening. In practice the only way to gain in sensitivity is to offer early recall to those who test negative on triage. The standard approach is to refer all HPV positive women with ay cytological abnormality to colposcopy and to recall those who have normal cytology at 6 or 12 months.
Whilst it is well known that, in the context of primary screening, cervical cytology is not the same in all laboratories there has been far less acknowledgement of the heterogeneity of cytology when it comes to HPV triage. Here we will look at the sensitivity and positive predictive value of using cytology (with different) cut-offs for HPV triage from studies carried out in different countries.
Although cytology is the norm for HPV triage, there is much interest in using molecular biomarkers either instead of or as an adjuvant to cytology. When used as an adjunct, most researchers have focused on improving the sensitivity of immediate referral for high-grade CIN (or CIN3+). In this talk I will argue that one should consider all those not referred immediately to colposcopy as triage-negative but should be willing to set a variable time for next screen depending on the result of al screening (and triage) tests. Additionally, I will argue that although the threshold for immediate colposcopy should be determined in terms of CIN3, the time to next screen should be set to try to equalise the risk of developing invasive cervical cancer in the interval.
Cytology triage of positive HPV depend on the quality and threhold of the cytology. Systematic reviews should not assume that performance is homogeneous.
It is rational to re-screen cytology normal women sooner if they are HPV16/18 positive than if they only have other high-risk HPV types. Women with high-grade cytology should be referred regardless of HPV type.
Triage protocols may need to be countriy-specific and should focus on both identifying those benefitting from immediate colposcopy and on extending the screening interval to as long as is safe in those not offered in immediate colposcopy. One size does not fit all.