Implementing specificity of HPV-DNA primary screening in a successful organised cervical cancer prevention programme

ObjectiveThis two-arm longitudinal study was performed within a regional organized cervical-cancer-prevention program in which HPV-DNA test is used in primary screening. The aim was to analyze the diagnostic performances of p16INK4a/Ki-67 dual-test and E6/E7-mRNA test in identifying CIN2 + lesion among HPV-DNA positive (HPV-DNAve) women triaged for LSIL-or-worse liquid based cytology (LBC).MethodsThirty-six thousand thirty-one women participated to HPV-DNA screening program pilot study. Three thousand six hundred forty-one resulted HPV-DNAve; among these, 43% were LSIL-or-worse (LSIL +). HPV-DNAve/LSIL + patients were submitted to colposcopy and histological assessment of any visible lesions.Dual-test was performed on 794 residual LBC specimens. In 405 cases, dual-test result was related to histology, considering CIN2 + as endpoint. mRNA test has been carried out retrospectively, on a subset of 173 residual LBC specimens.ResultsAgreement between dual-test and histological diagnosis was 59%. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of cytology-plus-dual-test approach were 62.3%, 76.8%, 63.1% and 84.2%, respectively. Dual-test improved specificity, PPV and NPV of cytological triage Agreement between mRNA testing and histology was 65%. Cytology-plus mRNA testing showing sensitivity, specificity, PPV and NPV reaching 32.1%, 94.9%, 75% and 50%, respectively; implemented specificity and PPV of cytology alone in triaging DNA-ve/LSIL + patients (p < 0.01).ConclusionsWe provided promising data indicating the important role that p16INK4/Ki-67 dual-test, and mostly E6/E7 mRNA test, might have in triaging HPV-DNAve. These approaches would exclude the occurrence of cervical cancer and would avoid overtreatment, at the same time. Further longitudinal analysis has to be considered.

► Longitudinal study performed within a Cervical Cancer Screening Program.
► The aim was to evaluate p16/Ki-67 dual-test and E6/E7-mRNA test.
► Cervical Cancer Screening may be improved by these tests.