Clinical Validation of the Cervista HPV HR Test According to the International Guidelines for Human Papillomavirus Test Requirements for Cervical Cancer Screening

Abstract

This study demonstrates that both the clinical sensitivity and specificity of the Cervista HPV HR test for high-risk human papillomavirus (HPV) detection are not inferior to those of the Hybrid Capture 2 (HC2) test. The intra-and interlaboratory reproducibilities of Cervista were 92.0% (kappa, 0.83) and 90.4% (kappa, 0.80), respectively. The Cervista HPV HR test fulfills all the international HPV test requirements for cervical primary screening purposes. It is well established that cervical cancer is caused by a persistent infection of cervical epithelial cells by any of the ϳ14 genotypes of high-risk human papillomavirus (hrHPV). This knowledge prompted the development of in vitro diagnostic tests for hrHPV testing in clinical specimens. Generally, these tests have a high sensitivity and high negative predictive value, making them potentially valuable tools for primary screening strategies. Systematic reviews have shown that primary screening using hrHPV testing has a higher sensitivity than that of cytology for detecting cervical intraepithelial neoplasia grade 2 or higher (CIN2ϩ) (1, 2). Although many current international guidelines limit HPV testing to the triage of borderline lesions and to post-CIN follow-up, it is believed that in the near future, HPV testing will be included in most European official guidelines as a viable strategy for primary screening (3). In line with the international guidelines for HPV DNA testing in primary cervical cancer screening in women Ն30 years described by Meijer et al. (4), the recently updated guidelines from the American Society for Colposcopy and Cervical Pathology (ASCCP) emphasize the importance of using a validated HPV test, i.e., an HPV test that has proven acceptable reproducibility, clinical sensitivity, specificity, and positive and negative predictive values for cervical cancer screening of CIN2ϩ lesions (5).The Cervista HPV HR test (Hologic, Inc., Madison, WI) was the second hrHPV assay approved by the FDA in 2009, 10 years after the approval of the Hybrid Capture 2 hrHPV DNA (HC2) test. The Cervista HPV HR assay uses Invader chemistry, a signal amplification method, to qualitatively detect specific nucleic acid sequences of 14 hrHPV types (HPV16,, as described previously (6), and it utilizes a primary reaction that occurs on the targeted DNA sequence and a secondary reaction that produces a fluorescent signal. Both types of reactions rely on oligonucleotide hybridization, invasive structure formation, and cleavage by the Cleavase enzyme. Interpretation of the HPV results was done in accordance with the Cervista HPV HR test package insert (7). The Cervista test has a few advantages over the HC2 test: it detects the same hrHPV types as the HC2 test plus HPV66, it requires half the sample volume of that of the HC2 test, it includes the human histone 2 gene as an internal control for sample adequacy, it demonstrates no cross-reactivity with common nononcogenic HPV types, and it has a shorter processing time. In comparative studies, the Cervista HPV HR test shows ...

Cervical cancer screening using the Cervista high-risk human papillomavirus test: opportunistic screening of a hospital-based population in Fujian province, China

“… 28 The Cervista HPV HR test was the second HR-HPV assay approved by the FDA in 2009 and introduced into China by the China Food and Drug Administration (CFDA) in 2011, with a similar sensitivity and specificity to those of the HC2 test. 23 However, the clinical performance of Cervista as a primary HPV screening method, especially in a Chinese hospital-based population, has remained uncertain.…”

“…The Cervista HPV HR test was the second HR-HPV assay approved by the FDA in 2009 and is a qualitative test that uses three separate oligonucleotide mixtures (A5/A6 pool [HPV 51, 56, and 66], A7 pool [18, 39, 45, 59, and 68], and A9 pool [HPV 16, 31, 33, 35, 52, and 58]) depending on the correlation among 14 types of HR-HPV DNA gene sequences used to detect HR-HPV types. 23 The Cervista test detects 14 HR-HPV types: HPV66 and the same 13 HR-HPV types as detected by HC2 testing, and several comparative studies have shown its similar sensitivity and specificity to those of the HC2 test. 23 However, the utility of the Cervista HPV test as a primary HPV screening method and the clinical performance of different cervical cancer screening strategies, particularly in the Chinese population, remains unclear.…”

“… 23 The Cervista test detects 14 HR-HPV types: HPV66 and the same 13 HR-HPV types as detected by HC2 testing, and several comparative studies have shown its similar sensitivity and specificity to those of the HC2 test. 23 However, the utility of the Cervista HPV test as a primary HPV screening method and the clinical performance of different cervical cancer screening strategies, particularly in the Chinese population, remains unclear. This study was designed to provide evidence of the efficiency of a cervical cancer screening strategy using the Cervista HPV test for the detection of cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) and CIN3 or more severe (CIN3+) in a Chinese hospital-based population.…”

Clinical validation of full genotyping CLART® HPV4S assay on SurePath and ThinPrep collected screening samples according to the International Guidelines for Human Papillomavirus Test Requirements for Cervical Screening

“…The CLART® HPV4S (CLART4S) assay is a newly developed full-genotyping assay detecting 14 oncogenic (16,18,31,33,35,39,45,51,52,56,58,59,66,68) and two non-oncogenic HPV genotypes (6,11). It was evaluated using SurePath and ThinPrep screening samples collected from the Danish and Swedish cervical cancer screening programs, respectively.…”

Referral population studies underestimate differences between human papillomavirus assays in primary cervical screening

“…Other, newer, HPV assays will most likely not be submitted to similarly rigorous but costly and time‐consuming randomised trials. Instead, their accuracy of detecting high‐grade cervical intraepithelial neoplasia (CIN), a treatable screening endpoint, has been compared to that of HC2 or GP5+/6+ in several smaller, predominantly split‐sample, studies …”