Enzyme-linked immunosorbent assay for p16INK4a - A new triage test for the detection of cervical intraepithelial neoplasia?
Department of Gynaecology and Obstetrics, Hannover Medical School, Hannover, Germany.Acta Obstetricia Et Gynecologica Scandinavica (Impact Factor: 2.43). 02/2013; 92(2). DOI: 10.1111/aogs.12032
Objective. To evaluate enzyme-linked immunosorbent assay (ELISA) for cyclin-dependent kinase inhibitor 2A protein (p16INK4a) on self-collected cervicovaginal lavage samples as an additional triage test to identify women with high-grade cervical intraepithelial neoplasia (CIN). Design. Retrospective feasibility, sensitivity and specificity study. Setting. University Medical School, Germany. Sample. One hundred and fifty-two patients from the colposcopy clinic were included. Methods. All women used a cervico-vaginal lavage device (Delphi Screener) for self-sampling and had gynecological examinations with Pap smears, cervical smears in ThinPrep PreservCyt solution and Cervatec medium for human papillomavirus (HPV) testing (Qiagen Hybrid Capture 2) and colposcopic examinations with biopsies if abnormalities were detected (72 women; 51%). All cytological samples were examined by p16INK4a ELISA. Main outcome measures. Sensitivity and specificity of p16INK4a ELISA for high-grade CIN. Results. Complete data were available for 140 women. Among these, 62 women (46%) presented with an atypical Pap smear and 65 (46.4%) were high-risk HPV positive in the reference smear sample. Seventeen women (12%) had CIN 3+. Twenty-seven (19%) physician-collected samples were p16INK4a ELISA positive. In contrast, p16INK4a ELISA turned out to be positive in only one (1%) vaginal lavage sample. Conclusions. Our study shows that self-sampling with cervicovaginal lavage followed by p16INK4a ELISA is not suitable for the detection of high-grade CIN.
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ABSTRACT: Self-collection of cervical samples for human papillomavirus (HPV) testing can help to raise the participation rate in cervical cancer screening among non-responders. This study was conducted to compare the analytical and clinical performance of the Abbott RealTime High-Risk HPV Test (RealTime) with the Hybrid Capture 2 assay (HC2) on self-collected cervicovaginal lavage samples. One hundred samples from women referred for colposcopy (reference smears and biopsies in case of abnormalities) were included. Fifty-seven women had a normal cytology, 27 had low grade and 16 had high grade squamous intraepithelial lesions. Fourteen of 49 biopsies (28.6%) were benign, 14 (28.6%) cervical intraepithelial neoplasia 1, 11 (22.4%) cervical intraepithelial neoplasia 2, 8 (16.3%) cervical intraepithelial neoplasia 3 and 2 (4.1%) invasive cancer. The agreement between RealTime and HC2 in the self-collected and in the reference samples was 85% (κ=0.665) and 83% (κ=0.620), respectively. The agreement between self-sampling and the reference smears was higher with RealTime (93%; κ=0.849) than with HC2 (89%; κ=0.741). In the self-collected samples, the sensitivity and specificity for cervical intraepithelial neoplasia 2 or worse of RealTime/HC2 were 81.0%/66.7% (p=0.25) and 53.6%/57.1%, respectively. The sensitivity for cervical intraepithelial neoplasia 3 or worse of RealTime and HC2 were 80.0% and 70.0% (p=1.0). The specificity for cervical intraepithelial neoplasia 3 or worse was 43.6% (RealTime) and 51.3% (HC2). This study shows that RealTime can be used for HR-HPV testing of self-collected lavage samples in a referral population with at least equal quality and performance as HC2.
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ABSTRACT: Screening for human papillomavirus (HPV) infection is more effective in reducing the incidence of cervical cancer than screening using Pap smears. Moreover, HPV testing can be done on a vaginal sample self-taken by a woman, which offers an opportunity to improve screening coverage. However, the clinical accuracy of HPV testing on self-samples is not well-known. We assessed whether HPV testing on self-collected samples is equivalent to HPV testing on samples collected by clinicians. We identified relevant studies through a search of PubMed, Embase, and CENTRAL. Studies were eligible for inclusion if they fulfilled all of the following selection criteria: a cervical cell sample was self-collected by a woman followed by a sample taken by a clinician; a high-risk HPV test was done on the self-sample (index test) and HPV-testing or cytological interpretation was done on the specimen collected by the clinician (comparator tests); and the presence or absence of cervical intraepithelial neoplasia grade 2 (CIN2) or worse was verified by colposcopy and biopsy in all enrolled women or in women with one or more positive tests. The absolute accuracy for finding CIN2 or worse, or CIN grade 3 (CIN3) or worse of the index and comparator tests as well as the relative accuracy of the index versus the comparator tests were pooled using bivariate normal models and random effect models. We included data from 36 studies, which altogether enrolled 154 556 women. The absolute accuracy varied by clinical setting. In the context of screening, HPV testing on self-samples detected, on average, 76% (95% CI 69-82) of CIN2 or worse and 84% (72-92) of CIN3 or worse. The pooled absolute specificity to exclude CIN2 or worse was 86% (83-89) and 87% (84-90) to exclude CIN3 or worse. The variation of the relative accuracy of HPV testing on self-samples compared with tests on clinician-taken samples was low across settings, enabling pooling of the relative accuracy over all studies. The pooled sensitivity of HPV testing on self-samples was lower than HPV testing on a clinician-taken sample (ratio 0·88 [95% CI 0·85-0·91] for CIN2 or worse and 0·89 [0·83-0·96] for CIN3 or worse). Also specificity was lower in self-samples versus clinician-taken samples (ratio 0·96 [0·95-0·97] for CIN2 or worse and 0·96 [0·93-0·99] for CIN3 or worse). HPV testing with signal-based assays on self-samples was less sensitive and specific than testing on clinician-based samples. By contrast, some PCR-based HPV tests generally showed similar sensitivity on both self-samples and clinician-based samples. In screening programmes using signal-based assays, sampling by a clinician should be recommended. However, HPV testing on a self-sample can be suggested as an additional strategy to reach women not participating in the regular screening programme. Some PCR-based HPV tests could be considered for routine screening after careful piloting assessing feasibility, logistics, population compliance, and costs. The 7th Framework Programme of the European Commission, the Belgian Foundation against Cancer, the International Agency for Research on Cancer, and the German Guideline Program in Oncology.
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ABSTRACT: Cytology is a widely used method of triaging women who test positive for human papillomavirus (HPV). However, self-sampled specimens, which can substantially increase participation in screening programmes, are not suitable for accurate cytological assessment. We investigated whether direct DNA methylation-based molecular triage on self-sampled cervicovaginal specimens was non-inferior to cytology triage on additional physician-collected cervical samples in the detection of cervical intraepithelial neoplasia grade 2 (CIN2) or worse in women who did not attend cervical screening programmes.
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