Performance of HPV E6/E7 mRNA Assay as Primary Screening Test. Results from the NTCC2 Trial
Mené en Italie auprès de 41 127 femmes participant à un programme de dépistage du cancer du col de l'utérus, cet essai évalue la performance, du point de vue de la détection de lésions cervicales intraépithéliales, d'un test de dépistage recherchant l'ARN messager des protéines E6/E7 du papillomavirus humain (HPV) par rapport à un test de recherche de l'ADN du HPV
As the primary screening test, E6/E7 mRNA has shown similar sensitivity for CIN3+ and lower positivity rate than the HPV DNA test. Nevertheless, the overall mRNA positivity is too high for immediate colposcopy, making a triage test necessary. The aim was to estimate the mRNA performance as a primary test with different triage strategies. All HPV DNA-positives were tested for mRNA, cytology and p16/ki67. A sample of HPV DNA-negatives were also tested for mRNA to estimate test specificity. We included all CIN3+ histologically diagnosed within 24 months since recruitment.
Of the 41127 participants, 7.7% were HPV DNA-positive, of which 66.4% were mRNA-positive. Among the HPV DNA-negatives, 10/1108 (0.9%) were mRNA-positive. Overall, 97 CIN3+ were found. If mRNA was used as the primary test, it would miss about 3% of all CIN3+ with a 22% reduction of positivity compared to HPV DNA. The weighted specificity estimate for <CIN2 was 94.5% (95% CI=93.9%-94.9%) and sensitivity for CIN3+ was 96.9% (95% CI=91.3%-99.1%). If all the weighted estimated 6.0% mRNA-positive women had been referred to colposcopy, PPV for CIN3+ would have been 4.2%. Cytology or p16/ki67 triage would decrease immediate referral to 1.7% and 2.0%, increasing PPV to 11.2% and 11.7%, respectively; total colposcopy referral would be 4.0% and 3.9%, respectively.
As the primary screening test, the mRNA assay showed a positivity rate lower than that of HPV DNA, with a small number of CIN3+ missed. Triage with cytology or p16/ki67 would only marginally decrease overall colposcopy referral.
International Journal of Cancer , résumé, 2022