Comparison of Clinical Performance of Abbott RealTi m e High Risk HPV Test with That of Hybrid Capture 2 Assay in a Screening Setting

Abstract

The noninferiority score test revealed that the clinical sensitivity and specificity of the Abbott RealTime HR HPV test were not inferior (P ‫؍‬ 0.004 and 0.009, respectively) to those of HR HC2. Overall agreement between the two assays was 96.5%, with a k value of 0.86 (CI 95%, 0.82 to 0.91). We evaluated the intralaboratory reproducibility by retesting 521 samples at least 4 weeks after the first test; the crude agreement between the first and second test was 98.5%, with an overall k value of 0.97 (CI 95%, 0.95 to 0.99). This test fully satisfies the requirements of a primary cervical cancer screening test. This assay differentiates between HPV16, HPV18, and non-HPV16/18 types in every specimen, but how to use this information in a screening setting still is unclear.The etiologic link between persistent high-risk human papillomavirus (HR HPV) infections and cervical cancer and its immediate precancerous lesions has been widely demonstrated. A recent IARC classification reports solid evidence for a causal link to cervical cancer for only 12 HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59), which are defined as high-risk HPV (2).Large randomized trials produced sound evidence about the efficacy of screening with an HPV DNA test in reducing cervical cancer incidence (19) and mortality (20). According to trial results, an HPV test used as a cervical cancer screening test has three advantages: a higher long-term negative predictive value (NPV) that permits extending the screening interval without increasing the interval risk of cancer, a clinical sensitivity of 90 to 95% for cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) (1,3,6,7,13,17,18), and a marked reduction of CIN2/3 and cancer among test-negative women in the subsequent screening round (19).Several studies (12, 21) suggest that infections supported by HPV16 and HPV18 are associated with a higher risk for the progression of cervical cancer. Consequently, the genotyping of HPV16 and HPV18 has been proposed to guide the management of HPV-positive women throughout the follow-up procedures (12). Usually, viral tests are used to understand the etiology of symptomatic diseases. However, the HR HPV test in screening is aimed at preventing cervical cancer in an asymptomatic population, therefore it is useful only when it is able to detect clinically relevant infections. In other words, HPV testing for screening purposes needs optimal balance between clinical sensitivity and specificity. At present, the HPV assays considered clinically validated for screening purposes are the hybrid capture 2 HPV test (HC2) and the GP5ϩ/6ϩ-PCR enzyme immunoassay (EIA) (24). New candidate assays should prove their value in large prospective screening studies or should prove to be noninferior to a validated reference assay in clinical equivalence studies on specimens from a cervical screening cohort. An international consortium recently published guidelines (14) defining the appropriate study design and sample size to measure the sensitivity, specificity, and re...

Comparison of Seegene Anyplex II HPV28 with the PGMY-CHUV Assay for Human Papillomavirus Genotyping

“…In addition, knowledge of the step at which the melting curve becomes positive allows us to semiquantify the viral load, from low (ϩ; positive after 40 PCR cycles), to intermediate (ϩϩ; positive within 31 to 39 cycles), to high (ϩϩϩ; positive before 31 cycles). H28 thus distinguishes semiquantitatively 28 HPV genotypes (6,11,16,18,26,31,33,35,39,40,42,43,44,45, 51, 52, 53, 54, 56, 58, 59, 61, 66, 68, 69, 70, 73, and 82) in only 2 reactions by taking advantage of the 5 dyes that can be resolved on the CFX96 real-time PCR instrument (Bio-Rad; provided together with the H28 kits by BÜ HLMANN Laboratories AG, Schönen-buch, Switzerland). Data recording and interpretation were automated with the Seegene viewer software according to the manufacturer's instructions.…”

“…Assays that have been clinically validated identify high-risk genotypes as a whole (the hybrid capture II [HCII] assay) or distinguish HPV16 or HPV18 from the other high-risk types as a group (HPV31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, and -68) (Abbott RealTime high-risk HPV and Roche Cobas 4800 HPV tests). The Abbott and Roche tests have been validated against HCII using cervical intraepithelial neoplasia (CIN) grade 2 or higher as endpoints (6)(7)(8). They were also found in these studies to be suitable for primary cervical cancer screening according to published guidelines (9).…”

The Value of Partial HPV Genotyping After Conization of Cervical Dysplasias

“…Such non-inferiority has been shown for the Abbott RealTime High Risk HPV Test (RealTime; Abbott, Wiesbaden, Germany), a PCR-based HPV detection method, in studies by Poljak et al [17] and Carozzi et al [18].…”

“…The two test methods evaluated in our study, hc2 and RealTime, were shown to have clinical sensitivity and specificity of 100 and 78.8 % (hc2)/specificity 84. 8 [17,18,22]). Similar to our findings these studies also found a tendency towards higher specificity for RealTime compared to hc2 and higher clinical sensitivity for hc2.…”

“…The International Agency for Research on Cancer (IARC) classifies 12 (16,18,31,33,35,39,45, 51, 52, 56, 58 und 59) of the 150 HPV types as class one carcinogens. Genotypes 16 and 18 are among the most common worldwide and are found in over 70 % of squamous cell carcinomas (85 % of CC) and in over 80 % of adenocarcinomas and adenosquamous carcinomas (15 % of CC) [1][2][3][4].…”