Sensitivity, Specificity, and Clinical Value of Human Papillomavirus (HPV) E6/E7 mRNA Assay as a Triage Test for Cervical Cytology and HPV DNA Test

Abstract

There is evidence that testing for human papillomavirus (HPV) E6/E7 mRNA is more specific than testing for HPV DNA. A retrospective study was carried out to evaluate the performance of the PreTect HPV-Proofer E6/E7 mRNA assay (Norchip) as a triage test for cytology and HPV DNA testing. This study analyzed 1,201 women, 688 of whom had a colposcopy follow-up and 195 of whom had histology-confirmed high-grade intraepithelial neoplasia or worse (CIN2؉). The proportion of positive results and the sensitivity and specificity for CIN2؉ were determined for HPV mRNA in comparison to HPV DNA and cytology. All data were adjusted for follow-up completeness. Stratified by cytological grades, the HPV mRNA sensitivity was 83% (95% confidence interval [CI] ‫؍‬ 63 to 94%) in ASC-US (atypical squamous cells of undetermined significance), 62% (95% CI ‫؍‬ 47 to 75%) in L-SIL (low-grade squamous intraepithelial lesion), and 67% (95% CI ‫؍‬ 57 to 76%) in H-SIL (high-grade squamous intraepithelial lesion). The corresponding figures were 99, 91, and 96%, respectively, for HPV DNA. The specificities were 82, 76, and 45%, respectively, for HPV mRNA and 29, 13, and 4%, respectively, for HPV DNA. Used as a triage test for ASC-US and L-SIL, mRNA reduced colposcopies by 79% (95% CI ‫؍‬ 74 to 83%) and 69% (95% CI ‫؍‬ 65 to 74%), respectively, while HPV DNA reduced colposcopies by 38% (95% CI ‫؍‬ 32 to 44%) and by 15% (95% CI ‫؍‬ 12 to 19%), respectively. As a HPV DNA positivity triage test, mRNA reduced colposcopies by 63% (95% CI ‫؍‬ 60 to 66%), having 68% sensitivity (95% CI ‫؍‬ 61 to 75%), whereas cytology at the ASC-US؉ threshold reduced colposcopies by 23% (95% CI ‫؍‬ 20 to 26%), showing 92% sensitivity (95% CI ‫؍‬ 87 to 95%). In conclusion, PreTect HPV-Proofer mRNA can serve as a better triage test than HPV DNA to reduce colposcopy referral in both ASC-US and L-SIL. It is also more efficient than cytology for the triage of HPV DNA-positive women. Nevertheless, its low sensitivity demands a strict follow-up of HPV DNA positive-mRNA negative cases.

E6/E7 proteins are potential markers for the screening and diagnosis of cervical pre‑cancerous lesions and cervical cancer in a Chinese population

“…According to the present results, the application of E6/E7 protein detection in CC screening could reduce the limitations of other recent technologies, such as the Pap test and HC2 test, and the indicators (E6/E7 proteins) for both cervical pre-cancer and progression to CC could be quantified with the standard detection method established in the present study (17,21). However, not all types of anti-E6/E7 monoclonal antibodies exhibit high specificity currently (8,38).…”

“…According to previous studies on HPV mRNA, the sensitivity and specificity of E6/E7 mRNA detection for patients with CIN2 + plus ASC-US or LSIL or ASC-US/LSIL were statistically similar for different types of HPV, ranging from 66.0 to 86.8%, and from 52.2 to 82.0%, respectively (21)(22)(23).…”

“…The sensitivity and specificity of E6/E7 protein detection for CIN2 + patients with HSIL and positive HPV DNA testing were 71.8 and 58.3%, respectively (Table IV), while E6/E7 mRNA testing exhibited higher specificity and similar sensitivity compared with those of E6/E7 protein detection. According to previous studies on HPV mRNA detection, there may be no significant differences in terms of sensitivity or specificity between the screening indicators of E6/E7 mRNA and E6/E7 protein detection (21). However, the PPV in the E6/E7 protein test was higher than the NPV, while the NPV in the E6/E7 mRNA test was higher than the PPV.…”

High-Risk Human Papillomavirus (hrHPV) E6/E7 mRNA Testing by PreTect HPV-Proofer for Detection of Cervical High-Grade Intraepithelial Neoplasia and Cancer among hrHPV DNA-Positive Women with Normal Cytology

“…This suggests a higher specificity of this mRNA assay for high-grade cervical lesions compared to HPV DNA assays. The clinical performance of the PreTect HPV-Proofer test as a triage test for cytology and/or HPV DNA testing has been determined in various studies (4,5,10,31,32,38,39), but it has not yet been extensively evaluated in women participating in population-based cervical screening.…”

Overview on Molecular Markers to Implement Cervical Cancer Prevention: Challenges and Perspectives

“…DNA and RNA test showed identical sensitivity to detect CIN2+ lesion, but the specificity for RNA and DNA test was 85% and 50% respectively. (Benevolo et al, 2011).…”