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

Abstract

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.

Increased risk for development of severe cervical dysplasia among postmenopausal women with normal cytology and presence of HPV mRNA

“…A cohort study with longterm follow-up could demonstrate that the five year cumulative risk of developing CIN 3 or worse was comparable between the cohort of HPV DNA negative and HPV mRNA negative women (22). Those clinical data lead to the assumption that the implementation of four year screening intervals is a safe strategy in HR-HPV mRNA negative women like it is already reported for HR-HPV DNA negative women aged 40 years or older (20,23,24).…”

14-type HPV mRNA test in triage of HPV DNA positive postmenopausal women with normal cytology

“…A cohort study with longterm follow-up could demonstrate that the ve year cumulative risk of developing CIN 3 or worse was comparable between the cohort of HPV DNA negative and HPV mRNA negative women 28 . Those clinical data lead to the assumption that the implementation of four year screening intervals is a safe strategy among HR-HPV mRNA negative women (Figure 4), similar to HR-HPV DNA negative women aged 40 years or older 18,29,30 .…”

14-type HPV mRNA test in triage of HPV DNA-positive postmenopausal women with normal cytology

“…A cohort study with long-term follow-up was able to demonstrate that the five-year cumulative risk of developing CIN 3 or worse was comparable between the cohort of HPV DNA-negative and HPV mRNA-negative women [28]. Those clinical data lead to the assumption that the implementation of four-year screening intervals is a safe strategy among HR-HPV mRNA-negative women (Fig.…”