Background
The study presents cross-sectional accuracy of E6/E7 mRNA detection and p16/ki67 dual staining, alone or in combination with cytology and HPV16/18 genotyping, as triage test in HPV DNA-positive women and their impact on CIN2+ overdiagnosis.
Methods
Women aged 25-64 were recruited. HPV DNA-positives were triaged with cytology and tested for E6/E7 mRNA and p16/ki67. Cytology positives were referred to colposcopy, while negatives were randomised to immediate colposcopy or to one-year HPV retesting. Lesions found within 24 months since recruitment were included. All p-values were two-sided.
Results
40,509 women were recruited and 3147 (7.8%) tested HPV DNA-positive; 174 CIN2+ were found: sensitivity was 61.0% (95% CI = 53.6 to 68.0), 94.4% (95% CI = 89.1 to 97.3), and 75.2% (95% CI = 68.1 to 81.6) for cytology, E6/E7 mRNA, and p16/ki67, respectively. Immediate referral was 25.6%, 66.8%, and 28.3%, respectively. Overall referral was 65.3%, 78.3%, and 63.3%. Cytology or p16/ki67 when combined with HPV16/18 typing reached higher sensitivity with a small impact on referral. Among the 2306 HPV DNA-positive/cytology-negative women, relative CIN2+ detection in those randomized at 1-year retesting vs. immediate colposcopy suggests a -28% CIN2+ regression (95% CI = -57% to + 20%); regression was higher in E6/E7 mRNA-negatives (pinteraction =.29). HPV clearance at 1 year in E6/E7 mRNA and in p16/ki67 negatives was about 2 times higher than in positive women (Pinteraction < .001 for both).
Conclusions
p16/ki67 showed good performance as triage test. E6/E7 mRNA showed the highest sensitivity, at the price of too high a positivity rate to be efficient for triage. However, when negative, it showed a good prognostic value for clearance and CIN2+ regression.
Objective To present the results of the first and second round human papilloma virus (HPV)-based screening programme in the Umbria region after three years. Methods From August 2010 to November 2011, the entire female population aged 35-64 in a local health district was invited for HPV testing (HPV-DNA cobas4800 on a liquid-based cytology sample). HPV-negative women were re-invited after three years. For HPV-positive women, a slide was prepared and interpreted. Positive cytologies were referred to colposcopy; negatives were referred to repeat HPV after one year. If HPV was persistently positive, women were referred to colposcopy; if negative, to normal screening. Indicators of the first and second round are compared with those of cytology screening in the same area in the preceding three years. Results Participation was 56.5%, the same as cytology (56.6%). HPV-positivity was 6.4% (396/6272), cytology triage positivity was 35.6%; 251 cytology negative women were referred to one-year HPV retesting, 84.1% complied, and 55.5% were positive. Total colposcopy referral was 4.1%, and for cytology 1%. The detection rate for cervical intraepithelial neoplasia grade 2 or more severe was 10‰, compared with 3.7‰ using cytology. After three years, HPV-positivity was 3.4% (129/3831), overall colposcopy referral was 2.3% (most at one-year follow-up), and detection rate was 0.5/1000. Conclusions The first round detection rate was more than twice that of cytology screening, while colposcopy referral increased fourfold. At the second round, the detection rate decreased dramatically, showing that longer interval and more conservative protocols are needed.
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