Head-to-Head Comparison of the RNA-Based Aptima Human Papillomavirus (HPV) Assay and the DNA-Based Hybrid Capture 2 HPV Test in a Routine Screening Population of Women Aged 30 to 60 Years in Germany

Abstract

f Testing for E6/E7 mRNA in cells infected with high-risk (HR) human papillomavirus (HPV) might improve the specificity of HPV testing for the identification of cervical precancerous lesions. Here we compared the RNA-based Aptima HPV (AHPV) assay (Hologic) and the DNA-based Hybrid Capture 2 (HC2) HPV test (Qiagen) to liquid-based cytology (LBC) for women undergoing routine cervical screening. A total of 10,040 women, 30 to 60 years of age, were invited to participate in the study, 9,451 of whom were included in the analysis. Specimens were tested centrally by LBC, the AHPV test, and the HC2 test, and women who tested positive on any test were referred for colposcopy. Genotyping was performed on all HR-HPV-positive samples. Test characteristics were calculated based on histological review. As a result, we identified 90 women with cervical intraepithelial neoplasia grade 2؉ (CIN2؉), including 43 women with CIN3؉. Sensitivity differences between the AHPV test and the HC2 test in detecting CIN2؉ (P ‫؍‬ 0.180) or CIN3؉ (P ‫؍‬ 0.0625) lesions were statistically nonsignificant. Of three CIN3 cases that were missed with the AHPV test, two cases presented lesion-free cones and one had a non-HR HPV67 infection. The specificity (<CIN2) and positive predictive value (CIN2؉) of the AHPV test were significantly higher (both P < 0.001) than those of the HC2 test. The overall agreement between the tests was substantial ( ‫؍‬ 0.77). Finally, we present results for several possible triage strategies, based on the primary screening test being either the AHPV test or the HC2 test. In summary, the AHPV assay is both specific and sensitive for the detection of high-grade precancerous lesions and may be used in primary cervical cancer screening for women >30 years of age.T he cervical cancer mortality rate in Germany has decreased dramatically since the introduction of gynecological screening for cervical cancer in 1971 (1). Annual opportunistic screening is performed by conventional cytology (Pap smear) and is covered by health insurance for women Ն20 years of age. Despite this extensive effort, 4,600 new cases of cervical cancer (and approximately 1,500 deaths attributable to cervical cancer) (2) and 150,000 cases of cervical cancer precursors (cervical intraepithelial neoplasia grade 3 [CIN3]) are diagnosed each year (3). Persistent infections with high-risk (HR) human papillomaviruses (HPVs) have been shown to be causal for the development of cervical precancerous lesions and cancer. This has led to the development and investigation of various HPV detection methods, and HR HPV testing in addition to cytology is now widely applied in cervical cancer screening programs (4-7). Three DNA-based and one RNAbased assay for HR HPV group detection and two HPV16/18 genotyping assays have been approved by the U.S. Food and Drug Administration (FDA) for cervical cancer screening (http://www.fda.gov /MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics /ucm330711.htm). These assays include the Digene Hybrid Capture 2 (HC2) high-risk ...

Sensitivity of APTIMA HPV E6/E7 mRNA test in comparison with hybrid capture 2 HPV DNA test for detection of high risk oncogenic human papillomavirus in 396 biopsy confirmed cervical cancers

“…The agreement between the two tests for the detection of HR HPV was also very high (Table ). Our observed sensitivity rates of both tests were similar to that of previously reported findings in referral and screening populations for detection of CIN2+ [Monsonego et al, ; Ratnam et al, ; Szarewski et al, ; Iftner et al, ]. Of the 396 cases of cervical cancer included in the study, the assays yielded discrepant results in only 11 (2.8%) cases, and were negative in 14 (3.5%) cases, indicating a very high level of sensitivity of both assays in detecting invasive cervical cancer (Table ).…”

HPV‐mRNA and HPV‐DNA detection in samples taken up to seven years before severe dysplasia of cervix uteri

“…This is in agreement with the high NPV (99.7%, 95% CI: 99.6–99.9) that was reported 6 years after negative HPV‐DNA testing in a joint European randomized screening trial . Furthermore, preliminary results after 6 years of follow‐up of 872 women with normal cytology, and with negative HPV‐mRNA and negative hybrid capture II test (Qiagen) at baseline demonstrated high NPV of 99.77% (95% CI; 99.1–99.9) and 99.85% (95% CI; 99.1–99.9) for absence of CIN3, respectively …”

Differential Detection of Human Papillomavirus Genotypes and Cervical Intraepithelial Neoplasia by Four Commercial Assays

“…This brings into focus the question of whether the management recommendations for HPV-positive women should be the same irrespective of which assay detected the infection. Studies agree in that, regardless of the assay used for primary screening, HPV-positive women should not be directly referred for colposcopy (26–28). For HC2-positive women from the Dutch VUSA-screen study, Rijkaart and colleagues proposed using cytological triage and to repeat cytology testing at 12 months postbaseline for triage-negative women (26).…”

“…In this setup, the addition of HPV genotyping would lead to a higher cumulative number of colposcopies but would not significantly decrease the risk of missing ≥CIN3 cases. On the other hand, Iftner and colleagues, using data from the German Aptima- and HC2-based screening study (27), and Wright and colleagues, using data from the U.S.-based ATHENA study evaluating the cobas assay (28), found that optimal triage strategies seemed to involve HPV 16/18 genotyping at baseline. In these two studies, follow-up testing of triage-negative women could not be further evaluated, as immediate colposcopy was recommended to all HPV-positive women (for study purposes).…”