Comparison of Seven Tests for High-Grade Cervical Intraepithelial Neoplasia in Women with Abnormal Smears: the Predictors 2 Study

Abstract

h High-risk human papillomavirus (HPV) DNA/RNA testing provides higher sensitivity but lower specificity than cytology for the identification of high-grade cervical intraepithelial neoplasia (CIN). Several new HPV tests are now available for this purpose, and a direct comparison of their properties is needed. Seven tests were evaluated with samples in liquid PreservCyt transport medium from 1,099 women referred for colposcopy: the Hybrid Capture 2 (Qiagen), Cobas (Roche), PreTect HPV-Proofer (NorChip), Aptima HPV (Gen-Probe), and Abbott RealTime assays, the BD HPV test, and CINtec p16INK4a cytology (mtm laboratories) immunocytochemistry. Sensitivity, specificity, and positive predictive value (PPV) were based on the worst histology found on either the biopsy or the treatment specimen after central review. Three hundred fifty-nine women (32.7%) had CIN grade 2؉ (CIN2؉), with 224 (20.4%) having CIN3؉. For detection of CIN2؉, Hybrid Capture 2 had 96.3% sensitivity, 19.5% specificity, and 37.4% PPV. Cobas had 95.2% sensitivity, 24.0% specificity, and 37.6% PPV. The BD HPV test had 95.0% sensitivity, 24.2% specificity, and 37.8% PPV. Abbott RealTime had 93.3% sensitivity, 27.3% specificity, and 38.2% PPV. Aptima had 95.3% sensitivity, 28.8% specificity, and 39.3% PPV. PreTect HPV-Proofer had 74.1% sensitivity, 70.8% specificity, and 55.4% PPV. CINtec p16INK4a cytology had 85.7% sensitivity, 54.7% specificity, and 49.1% PPV. Cytology of a specimen taken at colposcopy (mild dyskaryosis or worse) had 88.9% sensitivity, 58.1% specificity, and 50.7% PPV. Our study confirms that, in a referral setting, HPV testing by a number of different tests provides high sensitivity for high-grade disease. Further work is needed to confirm these findings in a routine screening setting. High-risk (HR) human papillomavirus (HPV) is a necessary factor for the development of cervical cancer (31), but the presence of HR HPV DNA does not invariably lead to disease. We have shown that the detection of HR HPV DNA provides high sensitivity but has lower specificity than cytology for the identification of high-grade cervical lesions in a screening population in the United Kingdom (9), and this finding has been replicated in several other studies (1, 3, 8, 15-17, 21, 22, 26, 27). In addition, prospective studies have shown that HPV DNA-positive women who do not have disease initially are significantly more likely to develop high-grade squamous intraepithelial lesions (SILs) within 10 years than women with a negative HPV DNA test (4,12,14,18). If testing for HR HPV DNA is to be used as a primary cervical screening test, refinements or additional tests are highly desirable to improve its specificity while retaining its very high sensitivity. Candidates include HPV typing, detection of HPV E6/E7 mRNA tests, and p16INK4a cytology, which have shown higher specificity than HPV DNA testing (10,19).The introduction of a liquid-based medium for collection of cytological specimens has allowed other molecular techniques to be evaluated more easily as adjunc...

Human papillomavirus detection and genotyping, by HC2, full-spectrum HPV and molecular beacon real-time HPV assay in an Irish colposcopy clinic

“…As expected in this cohort of women with persistently abnormal cervical cytology smears, the prevalence of HPV was high by each of the assays at 83.3% for HC2, 91.9% for FS-HPV and 80.1% for MBRT-HPV, with adjusted high-risk only HPV detection rates of 61.4% for FS-HPV and 78.7% for MBRT-HPV (Table 1). Other studies which have examined prevalence of high-risk HPV infections in mixed colposcopy referral populations have noted high HPV prevalence rates regardless of the HPV DNA detection assay used (Cuschieri et al, 2014;Szarewski et al, 2012), indicating that most commercially available assays are sufficiently sensitive for HPV detection in this setting. The HC2 test and the FS-HPV had similar HPV detection rates across all grades of cytology whereas the MBRT-HPV had a much lower rate, which was probably associated with its lower analytical sensitivity for HPV 16, combined with the fact that HPV 16 was the most dominant HPV genotype overall.…”

Frequency of sexually transmitted diseases and main methodological implications

“…Tuttavia, la grande varietà di test che continuano ad essere immessi sul mercato per la diagnostica dell'HPV, è sostanzialmente dovuta all'assenza di un test ideale per la rilevazione e genotipizzazione di questo virus responsabile del cancro della cervice uterina (3). Le differenze principali tra i diversi test presenti sul mercato riguardano: a) la metodica usata (PCR-endpoint, utilizzata da gran parte dei test di genotipizzazione con ibridazione su striscia; Real-Time PCR, come l'Abbott RealTime High Risk HPV assay; tecnologia microarray, come l'Infiniti HPV assay dell'AutoGenomics), il tipo di target (DNA/RNA) e regione virale bersaglio (L1, E1, E6/E7), la diversa abilità di discriminare tra infezioni singole e multiple, la capacità più o meno limitata di individuare solo un certo numero di genotipi e di rilevare anche il DNA integrato (13,14,19,37,42). La positività all'HPV (tabella 6) rilevata nel nostro studio nella popolazione di screening primario (17.3%), mediante utilizzo del kit Innolipa Genotyping Extra, è risultata comparabile a quella riscontrata in numerosi studi effettuati in Europa e in Nord America, basati sull'utilizzo del test HC2 o di primers rivolti verso la regione L1 (13).…”

HPV33 DNA methylation measurement improves cervical pre-cancer risk estimation of an HPV16, HPV18, HPV31 and \textit{EPB41L3} methylation classifier

“…All women underwent coloposcopic examination, with biopsy and treatment as appropriate. The studies were approved by the local research ethics committees and all women analysed provided written consent and the study conforms with The Code of Ethics of the World Medical Association (Declaration of Helsinki), printed in the British Medical Journal (18 July 1964); full details are available elsewhere [17,18].…”