Determinants of viral oncogene E6-E7 mRNA overexpression in a population- based large sample of women infected by high-risk human papillomavirus types

Paolo Giorgi Rossi, Simonetta Bisanzi, Elena Allia, Alessandra Mongia, Francesca Carozzi, Anna Gillio-Tos, Laura De Marco, Guglielmo Ronco, Daniela Gustinucci, Annarosa Del Mistro, Helena Frayle, Anna Iossa, Giulia Fantacci, Giampaolo Pompeo, Elena Cesarini, Simonetta Bulletti, Basilio Passamonti, Martina Rizzi, Maria Gabriella Penon, Alessandra BarcaMaria Benevolo

Research output: Contribution to journalArticle

Abstract

Cervical cancer screening by human papillomavirus (HPV) DNA testing with cytology triage is more effective than cytology testing. Compared to cytology, the HPV DNA test's higher sensitivity, which allows better protection with longer intervals, makes it necessary to triage the women with a positive result to compensate its lower specificity. We are conducting a large randomized clinical trial (New Technologies for Cervical Cancer 2 [NTCC2]) within organized population-based screening programs in Italy using HPV DNA as the primary screening test to evaluate, by the Aptima HPV assay (Hologic), the use of HPV E6-E7 mRNA in a triage test in comparison to cytology. By the end of June 2016, data were available for 35,877 of 38,535 enrolled women, 2,651 (7.4%) of whom were HPV DNA positive. Among the samples obtained, 2,453 samples were tested also by Aptima, and 1,649 (67.2%) gave a positive result. The proportion of mRNA positivity was slightly higher among samples tested for HPV DNA by the Cobas 4800 HPV assay (Roche) than by the Hybrid Capture 2 (HC2) assay (Qiagen). In our setting, the observed E6-E7 mRNA positivity rate, if used as a triage test, would bring a rate of immediate referral to colposcopy of about 4 to 5%. This value is higher than that observed with cytology triage for both immediate and delayed referrals to colposcopy. By showing only a very high sensitivity and thus allowing a longer interval for HPV DNA-positive/HPV mRNA-negative women, a triage by this test might be more efficient than by cytology.
Original languageEnglish
Pages (from-to)1056-1065
Number of pages10
JournalJournal of Clinical Microbiology
Volume55
Issue number4
DOIs
Publication statusPublished - Apr 1 2017

Keywords

  • Biomarkers
  • Cervical cancer screening
  • HPV E6-E7 oncogene mRNA
  • Human papillomavirus

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    Rossi, P. G., Bisanzi, S., Allia, E., Mongia, A., Carozzi, F., Gillio-Tos, A., De Marco, L., Ronco, G., Gustinucci, D., Del Mistro, A., Frayle, H., Iossa, A., Fantacci, G., Pompeo, G., Cesarini, E., Bulletti, S., Passamonti, B., Rizzi, M., Penon, M. G., ... Benevolo, M. (2017). Determinants of viral oncogene E6-E7 mRNA overexpression in a population- based large sample of women infected by high-risk human papillomavirus types. Journal of Clinical Microbiology, 55(4), 1056-1065. https://doi.org/10.1128/JCM.01794-16