Alternative cytology triage strategies for primary HPV screening

Primary HPV screening programmes for cervical cancer have been implemented in many European countries using a cytology triage. Nonetheless, the optimal cytology triage strategy for minimizing the harms and maximizing the benefits is yet unclear. We identified key characteristics of different algorithms for HPV screening with cytology triage.

Using the Finnish randomized HPV screening trial data, we formulated five post-hoc algorithms for HPV screening with a cytology triage, one for HPV screening without a triage and one for cytology screening. Sensitivity, specificity, positive predictive value, colposcopy referral rate and cumulative sensitivity for CIN II + s detected during the first and second screening rounds of the trial were calculated for all algorithms.

In the first screening round, direct referral of HPV positives to colposcopy led to the highest sensitivity (94%) accompanied by the lowest specificity (93%). Following HPV positives up with one repeat screen showed 86% sensitivity and 97% specificity. The corresponding figures with two repeat screens were 84% and 98%. In HPV algorithms, where cytology negative HPV positive individuals had no follow-up, the sensitivities were 65-82% and the specificities 98-99%. The Cytology algorithm had a low sensitivity (69%) with a high specificity (99%). Compared to the first round, the second-round sensitivities were lower and specificities similar or higher.

The best balance between sensitivity and specificity was achieved by an HPV algorithm with two repeated follow-up tests. However, all HPV algorithms with cytology triage increased colposcopy volume more than the cytology algorithm and thus provoked overdiagnosis.