Comparison of oncogenic HPV type-specific viral DNA load and E6/E7 mRNA detection in cervical samples: Results from a multicenter study

作者:Broccolo Francesco*; Fusetti Lisa; Rosini Sandra; Caraceni Donatella; Zappacosta Roberta; Ciccocioppo Lucia; Matteoli Barbara; Halfon Philippe; Malnati Mauro S; Ceccherini Nelli Luca
来源:Journal of Medical Virology, 2013, 85(3): 472-482.
DOI:10.1002/jmv.23487

摘要

High-risk human papillomavirus (HR-HPV) genotype viral load and E6/E7 mRNA detection are proposed as surrogate markers of malignant cervical lesion progression. Currently, the use of commercially available DNA-based or mRNA-based tests is under investigation. In this study, the viral DNA load and E6/E7 mRNA detection of the five most common HR-HPV types detected in cervical cancer worldwide were compared in 308 cervical samples by using in-house type-specific quantitative real-time PCR assays and PreTect HPV-Proofer test, respectively. Sensitivity and negative predictive values were higher for the HPV-DNA assays combined (95.0% and 96.0%, respectively) than the RNA assays (77.0% and 88.0%, respectively); conversely, the mRNA test showed a higher specificity and higher positive predictive value (81.7% and 66.9%, respectively) than the DNA test (58.6% and 52.5%, respectively) for detecting histology-confirmed high-grade cervical intraepithelial neoplasia. A significantly higher association between viral DNA load and severity of disease was observed for HPV 16 and 31 (??=?0.62 and ??=?0.40, respectively) than for the other HPV types screened. A good degree of association between the two assays was found for detection of HPV 16 (k?=?0.83), HPV 18 (k?=?0.72), HPV 33 (k?=?0.66), and HPV 45 (k?=?0.60) but not for HPV 31 (k?=?0.24). Sequence analysis in L1 and E6-LCR regions of HPV 31 genotypes showed a high level of intra-type variation. HR-HPV viral DNA load was significantly higher in E6/E7 mRNA positive than negative samples (P?%26lt;?0.001), except for HPV 31. These findings suggest that transcriptional and replicative activities can coexist within the same sample. J. Med. Virol. 85:472482, 2013.

  • 出版日期2013-3