Dataset Information

Evaluation of Integrated HPV DNA as Individualized Biomarkers for the Detection of Recurrent CIN2/3 during Post-Treatment Surveillance.

ABSTRACT: Post-treatment follow-up in women with cervical pre-cancers (CIN3) is mandatory due to relapse in up to 10% of patients. Standard follow-up based on hrHPV-DNA/cytology co-testing has high sensitivity but limited specificity. The aim of our prospective, multicenter, observational study was to test the hypothesis that an individualized viral-cellular-junction test (vcj-PCR) combined with cytology has a lower false positive rate for the prediction of recurrence compared to standard co-testing. Pre-surgical cervical swabs served for the identification of HPV16/18 DNA integration sites by next-generation-sequencing (NGS). Samples taken at 6, 12 and 24 months post-surgery were evaluated by cytology, hrHPV-DNA and the patients' individual HPV-integration sites (vcj-PCR on the basis of NGS). Integration sites were detected in 48 of 445 patients (10.8%), 39 of them had valid follow-up data. The false positive rate was 18.2% (95% CI 8.6-34.4%) for standard hrHPV/cytology at six months compared to 12.1% (95% CI 4.8-27.3%) for vcj-PCR/cytology, respectively (McNemar p = 0.50). Six patients developed recurrences (1 CIN2, 5 CIN3) during follow-up. Standard co-testing detected all, whereas vcj-PCR/cytology detected only five patients with recurrences. Data of 269 patients without evidence of HPV16/18 integration were subject to post-hoc analyses. Standard co-testing revealed a false positive rate of 15.7% (95% CI 11.7-20.7%) and predicted ten of fourteen recurrences at six months. Although highly specific on its own vcj-PCR could not detect all recurrent CIN2/3. Possible reasons for this unexpected result may be multifocal lesions, intratumoral heterogeneity with respect to HPV integration and/or incident CIN.

SUBMITTER: Hoyer H

PROVIDER: S-EPMC8269020 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Evaluation of Integrated HPV DNA as Individualized Biomarkers for the Detection of Recurrent CIN2/3 during Post-Treatment Surveillance.

Hoyer Heike H Mehlhorn Grit G Scheungraber Cornelia C Hagemann Ingke I Hirchenhain Christine C Woelber Linn L Stolte Claudia C Hampl Monika M Scherbring Sarah S Denecke Agnieszka A Bartels Janina J Ebert Andreas D AD Meneder Sabina S Petzold Annett A Heller Tabitha T Heidtke Karsten R KR Schwarz Elisabeth E Stübs Frederik F Schütze Stefanie S Stange Eva-Lena EL Jaeger Anna A Martignoni Franca F Dellmann Ansgar A Rody Achim A Hillemanns Peter P Fehm Tanja T Petry Karl-Ulrich KU Böhmer Gerd G Schmalfeldt Barbara B Wimberger Pauline P Beckmann Matthias W MW Runnebaum Ingo B IB Dürst Matthias M

Cancers 20210701 13

<h4>Purpose</h4>Post-treatment follow-up in women with cervical pre-cancers (CIN3) is mandatory due to relapse in up to 10% of patients. Standard follow-up based on hrHPV-DNA/cytology co-testing has high sensitivity but limited specificity. The aim of our prospective, multicenter, observational study was to test the hypothesis that an individualized viral-cellular-junction test (vcj-PCR) combined with cytology has a lower false positive rate for the prediction of recurrence compared to standard ...[more]

PMID: 34282754

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Project description:IntroductionBladder cancer is the fourth most common cancer in men and the ninth most common cancer in women in Canada. Early detection of tumours is essential for improved prognosis and long-term survival. The standard method for detection and surveillance is cystoscopy together with urine cytology. Cystoscopy is relatively sensitive but is expensive and invasive. Urinary cytology is a noninvasive method that has poor sensitivity but high specificity; it is relied on for the detection of carcinoma in situ. Currently, several urinary-based bladder tumour biomarkers with USFDA/Health Canada approval are available commercially, but none have been widely adopted by urologists despite their offering high sensitivity and/or specificity. We present here a review of recent studies evaluating 7 commercial biomarker assays for the detection and/or surveillance of bladder cancer.ResultsSENSITIVITY AND SPECIFICITY RANGES, RESPECTIVELY, FOR EACH MARKER WERE REPORTED AS FOLLOWS: BTA Stat (Polymedco), 52.5%-78.0% and 69.0%-87.1%; BTA Trak (Polymedco), 51%-100% and 73%-92.5%; cytology, 12.1%-84.6% and 78.0%-100%; hematuria dipstick, 47.0%-92.6% and 51.0%-84.0%; NMP22 Bladder Cancer Test (Matritech), 34.6%-100% and 60.0%-95.0%; NMP22 BladderChek (Matritech), 49.5%-65.0% and 40.0%-89.8%; ImmunoCyt/uCyt+ (DiagnoCure), 63.3%-84.9% and 62.0%-78.1%; ImmunoCyt/uCyt+ and cytology, 81.0%-89.3% and 61.0%-77.7%; and UroVysion (Abbott Molecular)/florescence in situ hybridization, 68.6%-100% and 65.0%-96.0%.ConclusionWe find that no currently available bladder cancer urinary marker is sensitive enough to eliminate the need for cystoscopy. In addition, cytology remains integral to the detection of occult cancer. However, owing to their relatively high sensitivities, these markers may be used to extend the period between cystoscopies in the surveillance of patients with transitional cell carcinoma. Further study is required to determine which markers, alone or in panel, would best accomplish this.

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Dataset Information

Evaluation of Integrated HPV DNA as Individualized Biomarkers for the Detection of Recurrent CIN2/3 during Post-Treatment Surveillance.

Publications

Evaluation of Integrated HPV DNA as Individualized Biomarkers for the Detection of Recurrent CIN2/3 during Post-Treatment Surveillance.

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