Background: Cervical cancer is the second most commonly diagnosed cancer among women worldwide. Human papillomavirus (HPV) has been identified as a necessary but not sufficient cause in almost all invasive cervical cancer cases and recent attention has focused on the ability to detect the overexpression of HPV E6 and E7 oncogenes through mRNA testing. This study systematically reviews the literature on the accuracy of HPV mRNA testing and compares the test s performance to HPV DNA testing on the same patient samples. The Pre Tect Proofer (Norchip)/NucliSENS Easy Q (bioMérieux) and the APTIMA HPV assay (Gen-Probe) were identified as two commercial mRNA tests.
Methods: Bibliographic databases were searched from January 1996 through March 2010 which returned 2953 potentially relevant citations. Two reviewers assessed the references for relevance and selected ten manuscripts (nine studies) which met our inclusion criteria. Six studies investigated the performance of the Pre Tect Proofer/NucliSENS EasyQ, two studies investigated the performance of the APTIMA assay and one study investigated both mRNA tests on the same patient samples. The reference standard used to diagnose precancerous lesions was histologically confirmed cervical intraepithelial neoplasia 2+ (CIN2+). The methodological quality of the included studies was assessed in duplicate using QUADAS. Raw data was extracted independently and used to calculate sensitivity, specificity, positive and negative likelihood ratios, positive and negative predictive values and diagnostic odds ratios. Review Manager 5.0 software was used to fit a series of summary receiver operating characteristics (SROC) curves.
Results: The sensitivities ranged from 0.41 to 0.86 and from 0.90 to 0.95 for the Pre Tect Proofer and APTIMA assay, respectively. The specificities ranged from 0.63 to 0.97 and from 0.42 to 0.61 for the Pre Tect Proofer 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. Limitations include few primary studies, considerable heterogeneity and varying methodological quality of the included studies.
Conclusion: The synthesized evidence 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.