Evaluation of oncogenic human papillomavirus RNA and DNA tests with liquid‐based cytology in primary cervical cancer screening: The FASE study

Abstract

The APTIMA V R HPV Assay (AHPV) allows detection of 14 high-risk human papillomavirus (HPV) RNA types in cervical specimens. Until present, the assay has been compared to HPV DNA tests only in triage settings. Herein, we compare AHPV with a DNA assay (Hybrid Capture V R 2; HC2) and liquid-based cytology (LBC; using PreservCyt V R ThinPrep liquid Pap) in a screening setting (French APTIMA screening evaluation [FASE] study). Women (N 5 5,006) aged 20-65 were screened by gynecologists in 17 private practices in Paris, France. One cervical specimen was collected and tested with LBC, AHPV and HC2 assays. Women were referred to colposcopy if they were ASC-US1 in LBC or HPV positive in either HPV assay. To control for verification bias, a random group (14%) with normal LBC and dually HPV negative tests underwent colposcopy. Data from 4,429 women were analyzed. Sensitivity, specificity and predictive values were calculated for the three tests. AHPV and HC2 were highly sensitive for CIN21 (92.0% and 96.7%) and CIN31 (95.7% and 95.3%) detection and much more sensitive than LBC (69.1% for CIN21 and 73.3% for CIN31). Specificity of AHPV was higher than that of HC2, but similar to that of LBC (p < 0.001). Combining LBC with either HPV test slightly increased sensitivity but compromised specificity. AHPV assay is both specific and sensitive for the detection of high-grade precancerous lesions and may be considered as an option for routine cervical cancer screening for women over 20 years of age.Invasive cervical cancer (ICC) is the second most frequent female cancer worldwide, 1 with an estimation of 493,000 cases annually. ICC incidence and mortality rates have dramatically declined over the past five decades in developed countries, largely due to screening programs based on conventional cervical Papanicolaou (Pap) smears. 2,3 Conventional Pap smear screening, however, has limited sensitivity, positive predictive value (PPV) and reproducibility, which limits its use for primary screening. 3,4-7 Liquid-based cytology (LBC) has been shown to be more sensitive than conventional

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

“…The nonsignificantly lower sensitivity of the AHPV test in detecting CIN2ϩ (P ϭ 0.180) and CIN3ϩ (P ϭ 0.0625) is in line with earlier studies (11,12,17). However, more-recent reports demonstrate equal (10, 14-16) or higher (13,18) sensitivity of the AHPV test, compared to that of the HC2 test.…”

“…However, the poor sensitivity of cytology demands the development of more-accurate screening schemes. Strategies for the improvement of early diagnosis of CIN2ϩ cases have been assessed for the AHPV assay based on the primary screening test being cytology (10)(11)(12)(13)(14)(15)(16)(17)(18). Adjunctive testing to cytology, however, leads to reduced combined sensitivity.…”

“…The AHPV assay detects the HPV E6 and E7 mRNA of the 13 HR HPV types targeted by the HC2 assay as well as the class 2B type HPV66 (9). The AHPV test has been compared previously to the HC2 test (10)(11)(12)(13)(14)(15)(16)(17)(18); however, only three studies were conducted in a routine screening population (12,14,18) and only two of those studies performed a split-sample comparison with liquid-based cytology (LBC) and the HC2 test (12,14).…”

Overview on Molecular Markers to Implement Cervical Cancer Prevention: Challenges and Perspectives

“…FASE (French APTIMA Screening Evaluation) study was the first trial comparing Aptima mRNA test with LBC and HC2 (Monsonego et al, 2011). Data from about 4,500 Parisian women have been analyzed.…”

CerviCal Cytology, HPv DNa aND mrNa – a ComParative StuDy iN 162 PatieNtS

“…The incidence and mortality rates have declined over the past five decades in developed countries due to screening programs based on conventional cervical Papanicolaou (Pap) smears (4) . A draw-back of cytology is its limited power to predict which low-grade cervical lesions will progress to high-grade lesions in addition to a false-negative rate ranging from 20 to 30%, demonstrated in several studies in which a number of high-grade cervical lesions were missed (5,6) .…”