Objectives: Testing for HPV E6/E7 expression likely has greater clinical accuracy than HPV DNA testing for the detection of CIN2+. As part of a study in Canada assessing the application of E6/E7 mRNA and DNA testing in cervical cancer screening, longitudinal test sensitivity, and absolute risk for CIN2+ among those testing HPV positive at baseline were determined.

Methods: The study population was comprised of women referred to colposcopy. All were screened for HPV mRNA with APTIMA (Gen-Probe) and HPV-Proofer (Norchip) assays, and for HPV DNA with HC2 (Qiagen). LinearArray (Roche) was used for genotyping. Available colposcopy/histological data were collected from those who had normal colposcopy, negative histology, or CIN1 at baseline, for up to 30 months to assess disease outcome. Histology confirmed CIN2+ served as the disease endpoint. The baseline HPV results were correlated with the disease outcome.

Results: Of 344 patients in the study, 303 (88.1%) remained either negative, had persistent CIN1, or CIN1 regression. In this group, the specificity of APTIMA, HPV-Proofer, and HC2 was 41.3%, 74.9%, and 32.3%, respectively. Nineteen (5.5%) progressed to CIN1 from negative histology at baseline. In this subset, the sensitivity of APTIMA, HPV-Proofer, and HC2 was 57.9%, 42.1%, and 78.9%, respectively. Twenty two progressed from either a negative or CIN1 histology to CIN2 (n= 8) or CIN3 (n= 14). In this subset, the sensitivity of APTIMA, HPV-Proofer, and HC2 was 95.5%, 77.3%, and 100%, respectively. The absolute risk for CIN2+ among those with a positive APTIMA, HPV-Proofer, and HC2 at baseline was 10%, 16.8%, and 9.1%, respectively.

Conclusions: The HC2 assay showed the highest sensitivity to predict progression to CIN2+ but with the least specificity. E6/E7 mRNA negative CIN2+ cases could represent lesion regression. The absolute risk of developing CIN2+ was associated with the most common oncogenic HPV types found in cervical cancer.