Human papillomavirus load in Hybrid Capture II assay: Does increasing the cutoff improve the test?

Ordi, Jaume; Alonso, I.; Torné, Aureli; Esteve, Roser; Sierra, Erika; Campo, Elı́as; Puig-Tintoré, Luis M.

doi:10.1016/j.ygyno.2005.07.011

Cited by 37 publications

(30 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…TOP2A, an enzyme that unknots and decatenates DNA for DNA replication and cell cycle progression, demonstrated the best sensitivity (96%), being much higher than that of cytology and similar to that shown by high-risk HPV tests. 12,15 CDKN2A/p16 had the lowest sensitivity for HSIL diagnoses but had the highest specificity (69%) compared with other biomarkers. The combination of TOP2A and CDKN2A/p16 resulted in an adequate balance between sensitivity and specificity, and could be used in the identification of HSIL.…”

Section: Discussionmentioning

confidence: 92%

See 1 more Smart Citation

mRNA biomarker detection in liquid-based cytology: a new approach in the prevention of cervical cancer

Pino

Svanholm-Barrie²,

Torné

et al. 2015

Modern Pathology

Self Cite

View full text Add to dashboard Cite

Several high-risk human papillomavirus (HPV)-induced cell biomarkers have been proposed as possible candidates to identify patients harboring high-grade squamous intraepithelial lesions (HSILs) of the uterine cervix. We aimed to determine the feasibility of the detection of the mRNA of six biomarkers in cervical smear specimens obtained by liquid-based cytology and to evaluate whether this approach might be useful in the identification of patients with HSIL. One-hundred and twenty three women referred to colposcopy in the Hospital Clinic of Barcelona were included in the study. After a thorough study, including Pap test, high-risk HPV testing (Hybrid Capture 2 test), and colposcopy with directed biopsy and/or endocervical curettage, 48 patients were diagnosed with HSIL, whereas 75 were classified as negative (n ¼ 28), or harboring low-grade SIL (n ¼ 47). CDKN2A/p16, BIRC5, MMP9, TOP2A, MCM5, and MKI67 mRNA expression was analyzed by reverse transcription quantitative polymerase chain reaction in liquid-based cytology after the Pap test and Hybrid Capture 2 performance. The tissue expression of these biomarkers was analyzed by immunohistochemistry in the biopsy material. One-hundred and thirteen out of 123 (92%) liquid-based cytology yielded adequate material for mRNA analysis. TOP2A was the most sensitive (97%) biomarker for the detection of HSIL and CDKN2A/p16 the most specific (78%). The combination of TOP2A and CDKN2A/p16 showed a sensitivity of 96% (95% confidence interval (CI): 88-99) and a specificity of 71% (95% CI: 55-82). In the immunohistochemistry analysis, all biomarkers showed a high sensitivity but low specificity for HSIL, except CDKN2A/p16 which had a sensitivity of 100% and a specificity of 63%. The combination of TOP2A and CDKN2A/p16 showed a sensitivity of 100% (95% CI: 91-100) and a specificity of 43% (95% CI: 32-55). The detection of mRNA of cell biomarkers in liquid-based cytology material is feasible. The combination TOP2A and CDKN2A/p16 has a good balance between sensitivity and specificity for the detection of women with HSIL. Modern Pathology (2015) 28, 312-320; doi:10.1038/modpathol.2014.106; published online 5 September 2014Screening programs based on cervical cytology (Pap test) have led to a decrease in the incidence and the mortality by cervical cancer. However, the efficacy of cytological screening is hampered by the suboptimal sensitivity and interobserver variability of the conventional Pap test. 1,2 Although the introduction of liquid-based cytology has not led to improvements in terms of relative sensitivity for the detection of cervical cancer precursors, 3 this technique has enabled the use of adjunctive tests that may help to reduce the rate of false-negative cytological results and add objectivity to the classical morphological evaluation.High-risk human papillomaviruses (HPV) are the causative agents of cervical cancer, and high-risk HPV testing has shown to improve the sensitivity of the Pap test to over 95%. 4,5 However, high-risk HPV tests have a lower specificity than...

show abstract

Section: Discussionmentioning

confidence: 92%

“…A relative light unit of 1 (1.0 pg/ml) was used as the cut-off to classify a specimen as positive for high-risk HPV. 12 …”

Section: Liquid-based Cytology Histological Diagnosismentioning

confidence: 99%

mRNA biomarker detection in liquid-based cytology: a new approach in the prevention of cervical cancer

Pino

Svanholm-Barrie²,

Torné

et al. 2015

Modern Pathology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Conversely, Ordi et al (19) advocated the use of 1.0 RLU/ CO, since their data showed that increasing the cutoff level would not lead to an increase in specificity. However, the women in their study were selected on the basis of cytological abnormality (ASC-US or worse).…”

Section: Discussionmentioning

confidence: 99%

Cross-Sectional Comparison of an Automated Hybrid Capture 2 Assay and the Consensus GP5+/6+ PCR Method in a Population-Based Cervical Screening Program

Hesselink¹,

Bulkmans²,

Berkhof

et al. 2006

J Clin Microbiol

View full text Add to dashboard Cite

In this cross-sectional study, clinical performances of the hybrid capture 2 assay using an automated instrument (i.e., rapid capture system) (hc2-RCS) and the high-risk human papillomavirus GP5؉/6؉ PCRenzyme immunoassay (EIA) test were compared using cervical scrape specimens from 8,132 women that participated in a population-based screening trial. The hc2-RCS test scored significantly more samples positive (6.8%) than the GP5؉/6؉ PCR-EIA (4.8%) (P < 0.0005). This could be attributed largely to a higher positivity rate by the hc2-RCS test for women with cytologically normal, borderline, or mild dyskaryosis. A receiver operator characteristics analysis of the semiquantitative hc2-RCS results in relation to different cytology categories revealed that these differences are owing to differences in assay thresholds. For women classified as having moderate dyskaryosis or worse who also had underlying histologically confirmed cervical intraepithelial neoplasia grade 3 or cervical cancer (>CIN3), the hc2-RCS scored 97% (31/32) of samples positive, versus 91% (29/32) by GP5؉/6؉ PCR-EIA. However, this difference was not significant (P ‫؍‬ 0.25). After increasing the hc2-RCS cutoff from 1.0 to 2.0 relative light units/cutoff value of the HPV16 calibrator (RLU/CO), no additional CIN3 lesions were missed by hc2-RCS, but the number of test-positive women with normal, borderline, or mild dyskaryosis was significantly decreased (P < 0.0005). However, at this RLU/CO, the difference in test positivity between hc2-RCS and the GP5؉/6؉ PCR-EIA was still significant (P ‫؍‬ 0.02). The use of an RLU/CO value of 3.0 revealed no significant difference between hc2-RCS and GP5؉/6؉ PCR-EIA results, and equal numbers of smears classified as >CIN3 (i.e., 29/32) were detected by both methods. In summary, both assays perform very well for the detection of >CIN3 in a population-based cervical screening setting. However, adjustment of the hc2-RCS threshold to an RLU/CO value of 2.0 or 3.0 seems to produce an improved balance between the clinical sensitivity and specificity for >CIN3 in population-based cervical screening.

show abstract

“…A relative light units value of 1 (1.0 pg/ml) was used as the cutoff to classify and record each specimen as positive or negative. 23,24 The relative light units were recorded and used as a measure of viral load. 23,24 Histological Evaluation and Immunohistochemical Detection of p16…”

Section: Liquid-based Cytology and Hrhpv Testingmentioning

confidence: 99%

p16 staining has limited value in predicting the outcome of histological low-grade squamous intraepithelial lesions of the cervix

et al. 2016

Self Cite

View full text Add to dashboard Cite

In order to evaluate the usefulness of p16 staining in predicting the outcome of histological low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) we prospectively recruited all the patients referred to colposcopy from 2003 to 2011 due to abnormal screening test results and diagnosed with LSIL/CIN1 at biopsy (n = 507). All biopsies were stained for p16 and re-evaluated after three years by the same gynecological pathologist using the LAST criteria. Follow-up was conducted every 6 months and included a Pap test (liquid-based cytology), high-risk human papillomavirus testing (Hybrid Capture 2 test), and colposcopy. The mean follow-up was 28 months. An outcome diagnosis of HSIL was defined as a histological diagnosis of highgrade SIL/CIN (HSIL/CIN2-3). The diagnosis of LSIL/CIN1 was confirmed in 416 out of 507 biopsies (82%), whereas 58 (11%) were reclassified as negative and 33 (6%) as HSIL/CIN2-3. During follow-up, 86/507 women initially diagnosed with LSIL/CIN1 (17%) showed an outcome diagnosis of HSIL/CIN2-3, with the rate of HSIL final diagnosis of 3% (2/58) in the women with biopsies reclassified as negative, 17% (70/416) in the group with confirmed LSIL and 42% (14/33) in the women with biopsies reclassified as HSIL (Po 0.001). p16 was positive in 245/507 patients (48%) and in 210/416 patients (50%) with confirmed LSIL/CIN1 at re-evaluation. Although positive p16 immunostaining was associated with risk of HSIL/CIN2-3 outcome in the multivariate analysis (Hazard ratio (HR) 1.9; 95% confidence interval (CI): 1.2-3.1; P = 0.009) in the overall group of patients with LSIL/CIN1, this association was not verified in the subset of patients with confirmed LSIL/CIN1 after re-evaluation (HR: 1.6; 95% CI: 0.9-2.6; P = 0.095). In conclusion, in LSIL/CIN1 lesions p16 should be limited to equivocal cases in which HSIL/CIN2 is included in the differential diagnosis since it has low value in clinical practice as a marker of progression of LSIL/CIN1.

show abstract

Human papillomavirus load in Hybrid Capture II assay: Does increasing the cutoff improve the test?

Cited by 37 publications

References 32 publications

mRNA biomarker detection in liquid-based cytology: a new approach in the prevention of cervical cancer

mRNA biomarker detection in liquid-based cytology: a new approach in the prevention of cervical cancer

Cross-Sectional Comparison of an Automated Hybrid Capture 2 Assay and the Consensus GP5+/6+ PCR Method in a Population-Based Cervical Screening Program

p16 staining has limited value in predicting the outcome of histological low-grade squamous intraepithelial lesions of the cervix

Contact Info

Product

Resources

About