Direct Human Papillomavirus E6 Whole-Cell Enzyme-Linked Immunosorbent Assay for Objective Measurement of E6 Oncoproteins in Cytology Samples

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>A novel, whole-cell enzyme-linked immunosorbent assay (ELISA) based on a non-type-specific anti-human papillomavirus (HPV) E6 antibody was tested on 182 residual cytological specimens. For samples with a designation of more severe than<jats:italic>c</jats:italic>ervical<jats:italic>i</jats:italic>ntraepithelial<jats:italic>n</jats:italic>eoplasia grade 3 (CIN3+), 83% tested positive for E6; in a subset with paired testing for E6 ELISA and HPV DNA, 72% tested E6 positive and 92% tested high-risk (HR)-HPV DNA positive (<jats:italic>P</jats:italic>= 0.2). Among the women with a less than CIN3 diagnosis, 31% and 47% tested positive for E6 and HR-HPV DNA, respectively (<jats:italic>P</jats:italic>= 0.0006).</jats:p>

Triage of high-risk HPV positive women in cervical cancer screening

“…Development of the whole-cell enzyme-linked immunoabsorbent assay (ELISA) using an HPV16, 18 and 45 anti E6 monoclonal antibody to detect HPV E6 protein in cervical samples, could tackle this problem. In the first pilot-study as well as the first clinical trial and follow-up after 1 year, increased specificity with a considerable lower sensitivity for ≥CIN3 was found, compared to a hrHPV DNA test [76][77][78]. Clinical evaluation of the assay in triage of HC2 hrHPV-positive clinician-taken samples showed a high specificity for ≥CIN3 of 93.8% (95% CI 92.1-95.2), with again limited sensitivity of 54.2% (95% CI 43.7-64.4) [79].…”

A comparison of different human papillomavirus tests in PreservCyt versus SurePath in a referral population—PREDICTORS 4

“… OncoHealth (OncoHealth, San Jose, California) protein test is a direct E6/E7 HPV Whole-Cell ELISA carried out in microtitre wells and is based on detection by non-type specific HPV E6 and E7 monoclonal antibodies [14] . Relative Optical Density (ROD) was used compared to a reference value of 0.35.…”

Multicentre Evaluation of Hepika Test Clinical Accuracy in Diagnosing HPV-Induced Cancer and Precancerous Lesions of the Uterine Cervix

“…The Hepika test showed good sensitivity and specificity for invasive carcinoma, while its sensitivity for CIN3 and CIN2 was lower than that obtained by other biomarkers eligible for the HPV triage, such as cytology and p16/Ki67 dual staining (about 25% for Hepika and about 60–80% for the other biomarkers) [ 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. A commercially available test targeting specifically the E6 protein [ 48 ] showed much higher sensitivity for CIN3 than Hepika, but it also showed 50% positivity in HPV-positive/histology negative and 16% positivity in HPV negative samples. Such a low sensitivity excludes a possible use of Hepika as a triage test for HPV-positive women, because HPV-positive/Hepika-negative would require too strict a follow up given the high prevalence of CIN2 and CIN3 in this group.…”