5-type HPV mRNA versus 14-type HPV DNA test: test performance, over-diagnosis and overtreatment in triage of women with minor cervical lesions.

Bjørn Westre,Sveinung Wergeland Sørbye,Finn Egil Skjeldestad,Hilde Guttormsen,Anita Giske

doi:10.1186/s12907-016-0032-x

Bjørn Westre, Sveinung Wergeland Sørbye + Show 3 more

Open Access

https://doi.org/10.1186/s12907-016-0032-x

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Abstract

BackgroundRepeat cytology and HPV testing is used in triage of women with minor cytological lesions. The objective of this study was to evaluate 14-type HPV DNA and 5-type HPV mRNA testing in delayed triage of women with ASC-US/LSIL.MethodsWe compared a DNA test (Roche Cobas 4800) and an 5-type mRNA test (PreTect HPV-Proofer). In total 564 women were included in the study.ResultsThe sensitivity among solved cases for CIN3+ were 100 % (15/15) for both tests. The sensitivity for CIN2+ of the HPV DNA test was 100 % (38/38) relative to 79 % (30/38) for the 5-type HPV mRNA test. The corresponding estimates of specificity for CIN2+ among solved cases were 84 % (393/466; 95 % CI: 81–88) and 91 % (451/498; 95 % CI: 88–93). The positive predictive values for CIN3+ were 13.5 % (15/111) for DNA+ and 19.5 % (15/77) for 5-type mRNA+. Significantly more women screened with 5-type mRNA than DNA returned to screening (81 % vs 71 %, p < 0.01). Subsequently, significantly fewer women were referred for colposcopy/biopsies/treatment (19 % (105/564) vs 29 % (165/564), p < 0.01).Conclusions5-type HPV mRNA is more specific than 14-type HPV DNA in delayed triage of women with ASC-US/LSIL. The referral rate for colposcopy was 57 % higher for DNA+ relative to mRNA+ cases (165 vs 105), with the same detection rate of CIN3+, but the 5-type mRNA test had lower sensitivity for CIN2+. It is important to consider the trade-off between sensitivity and specificity of the diagnostic test when designing screening algorithms.

Highlights

Repeat cytology and human papillomavirus (HPV) testing is used in triage of women with minor cytological lesions
Our study shows that the 5-type HPV messenger ribonucleic acid (RNA) (mRNA) test had significantly lower positivity rate (19 %) than the 14-type HPV DNA test (29 %), which led to a significantly higher referral rate to colposcopy for the HPV DNA test
All these CIN2 cases were of HPV types other than 16/18 in both tests, and they were negative for HPV mRNA 31, 33, and 45

Summary

Introduction

Repeat cytology and HPV testing is used in triage of women with minor cytological lesions. The objective of this study was to evaluate 14-type HPV DNA and 5-type HPV mRNA testing in delayed triage of women with ASC-US/LSIL. The HPV E6/E7 mRNA test PreTect HPV-Proofer which detects HPV E6/E7 mRNA from the five most prevalent types causing cervical cancer has been shown to have a higher clinical specificity and positive predictive value (PPV) than HPV DNA tests [7,8,9,10,11,12,13,14]. In this study we performed a direct comparison of a 5-type HPV mRNA and a 14type HPV DNA test in delayed triage of ASC-US/LSIL related to referral rates for colposcopy, biopsy rates, and histological outcomes

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