HPV mRNA tests for the detection of cervical intraepithelial neoplasia: A systematic review

Objective. Perform a systematic review to determine the test performance of HPV mRNA testing compared to DNA testing using CIN2+ as the target condition. Methods. We searched bibliographic databases (MEDLINE, EMBASE and Cochrane Library) from January 1996 through August 2010 using a predefined search strategy. The reference standard used to diagnose precancerous lesions was histologically confirmed cervical intraepithelial neoplasia 2+ (CIN2+). Two reviewers independently assessed study eligibility, extracted data, and assessed risk of bias. Sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratios were calculated for each study. In addition, we fitted a series of summary receiver operating characteristics (SROC) curves. A subgroup analysis was performed according to specific inclusion covariates. Results. Out of 3179 potentially relevant citations, 12 publications (11 studies) met our inclusion criteria. The included studies were of varying methodological quality, and were predominately performed in a secondary screening setting. Eight studies investigated the performance of the PreTect Proofer/NucliSENS EasyQ two studies investigated the performance of the APTIMA assay and one study investigated both mRNA tests on the same patient samples. Due to few studies and considerable clinical heterogeneity, pooling of data was not possible. Instead, we compiled a 'best evidence synthesis' for E6/E7 mRNA HPV testing. Sensitivities ranged from 0.41 to 0.86 and from 0.90 to 0.95 for the PreTect Proofer/Easy Q and APTIMA assay, respectively. Specificities ranged from 0.63 to 0.97 and from 0.42 to 0.61 for the PreTect Proofer/Easy Q and APTIMA assay, respectively. The SROC curves for both mRNA tests were to the left of the diagonal and the APTIMA assay performed closest to the DNA tests. Conclusion. The review suggests that mRNA tests have diagnostic relevance, but additional studies and economic evaluations must be conducted in order to make a solid conclusion regarding the clinical applicability of HPV mRNA testing. (C) 2010 Elsevier Inc. All rights reserved.