Risk of CIN2 or more severe lesions after negative HPV-mRNA E6/E7 overexpression assay and after negative HPV-DNA test: Concurrent cohorts with a 5-year follow-up.

Aim of this study was to compare the 5-year risk of cervical intraepithelial neoplasia grade 2+ (CIN2+)/CIN3+ and the performance parameters at 3-year rescreening of a negative E6/E7 mRNA-human papillomavirus (HPV) test with those of a HPV-DNA-negative test. We studied a cohort of HPV-negative women tested with the Aptima HPV-mRNA Assay ("HPV-mRNA cohort") versus a cohort of HPV negatives tested with the Hybrid Capture 2 (HC2) DNA test living in neighboring areas. Both cohorts were rescreened after 3 years by a HPV-DNA test (HC2 or Cobas 4800 HPV test). HPV test positivity, referral to colposcopy and detection of CIN2+ at 3-year rescreening were computed. The Veneto Cancer Registry was checked to search for invasive cancers and CIN3 diagnosed up to 5 years from the negative baseline test. Some 22,338 HPV-mRNA and 68,695 HPV-DNA-negative women were invited to 3-year rescreening, and, respectively, 16,641 (74.5%) and 54,630 (79.6%) complied with the invitation. The proportion of HPV-positive tests, referral to colposcopy and detection of CIN2+ in the HPV-mRNA and HPV-DNA cohorts were, respectively. 4.0 and 3.9% (ratio 1.08; 95% confidence interval [CI] 0.99-1.17), 2.6 and 2.5% (ratio 1.06, 95% CI 0.95-1.18) and 1.4 and 1.7‰ (ratio 0.85, 95% CI 0.54-1.33). The relative 5-year cumulative risk of cancer and of CIN2+ in the HPV-mRNA and HPV-DNA cohorts were 4.5 and 8.7/100,000 (ratio 0.51; 95%CI 0.01-4.22) and 1.1 and 1.5/1,000 (ratio 0.74; 95%CI 0.45-1.16), respectively. A negative HPV-mRNA test confers a risk of invasive cervical carcinoma and of CIN2+ at 5 years comparable to that of a negative HPV-DNA test.

Screening women for cervical cancer carcinoma with a HPV mRNA test: first results from the Venice pilot program.

BACKGROUND: HPV DNA-based screening is more effective than a Pap test in preventing cervical cancer, but the test is less specific. New HPV tests have been proposed for primary screening. The HPV mRNA test showed a similar or slightly lower sensitivity than the HPV DNA tests but with a higher specificity. We report the results of an organised HPV mRNA-based screening pilot program in Venice, Italy. METHODS: From October 2011 to May 2014, women aged 25-64 years were invited to undergo a HPV mRNA test (Aptima). Those testing positive underwent cytological triage. Women with positive cytology were referred to colposcopy, whereas those with negative cytology were referred to repeat the HPV mRNA test 1 year later. The results of the HPV mRNA test program were compared with both the local historical cytology-based program and with four neighbouring DNA HPV-based pilot projects. RESULTS: Overall, 23 211 women underwent a HPV mRNA test. The age-standardised positivity rate was 7.0%, higher than in HPV DNA programs (6.8%; relative rate (RR) 1.11, 95% confidence interval (CI) 1.05-1.17). The total colposcopy referral was 5.1%, double than with cytology (2.6%; RR 2.02, 95% CI 1.82-2.25) but similar to the HPV DNA programs (4.8%; RR 1.02; 95% CI 0.96-1.08). The cervical intraepithelial neoplasia grade 2+ detection rate with HPV mRNA was greater than in the HPV DNA programs at baseline (RR 1.50; 95% CI 1.19-1.88) and not significantly lower at the 1-year repeat (RR 0.70; 95% CI 0.40-1.16). The overall RR was 1.29 (95% CI 1.05-1.59), which was much higher than with cytology (detection rate 5.5‰ vs 2.1‰; RR 2.50, 95% CI 1.76-3.62). CONCLUSIONS: A screening programme based on the HPV mRNA obtained results similar to those observed with the HPV DNA test. In routine screening programmes, even a limited increase in HPV prevalence may conceal the advantage represented by the higher specificity of HPV mRNA.