Evaluation of Integrated HPV DNA as Individualized Biomarkers for the Detection of Recurrent CIN2/3 during Post-Treatment Surveillance
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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; Mehlhorn, Grit; Scheungraber, Cornelia; Hagemann, Ingke; Hirchenhain, Christine; Woelber, Linn; Stolte, Claudia; Hampl, Monika; Scherbring, Sarah; Denecke, Agnieszka; Bartels, Janina; Ebert, Andreas D; Meneder, Sabina; Petzold, Annett; Heller, Tabitha; Heidtke, Karsten R; Schwarz, Elisabeth; Stübs, Frederik; Schütze, Stefanie; Stange, Eva-Lena; Jaeger, Anna; Martignoni, Franca; Dellmann, Ansgar; Rody, Achim; Hillemanns, Peter; Fehm, Tanja; Petry, Karl-Ulrich; Böhmer, Gerd; Schmalfeldt, Barbara; Wimberger, Pauline; Beckmann, Matthias W; Runnebaum, Ingo B; Dürst, Matthias.
in: CANCERS, Jahrgang 13, Nr. 13, 3309, 01.07.2021.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Evaluation of Integrated HPV DNA as Individualized Biomarkers for the Detection of Recurrent CIN2/3 during Post-Treatment Surveillance
AU - Hoyer, Heike
AU - Mehlhorn, Grit
AU - Scheungraber, Cornelia
AU - Hagemann, Ingke
AU - Hirchenhain, Christine
AU - Woelber, Linn
AU - Stolte, Claudia
AU - Hampl, Monika
AU - Scherbring, Sarah
AU - Denecke, Agnieszka
AU - Bartels, Janina
AU - Ebert, Andreas D
AU - Meneder, Sabina
AU - Petzold, Annett
AU - Heller, Tabitha
AU - Heidtke, Karsten R
AU - Schwarz, Elisabeth
AU - Stübs, Frederik
AU - Schütze, Stefanie
AU - Stange, Eva-Lena
AU - Jaeger, Anna
AU - Martignoni, Franca
AU - Dellmann, Ansgar
AU - Rody, Achim
AU - Hillemanns, Peter
AU - Fehm, Tanja
AU - Petry, Karl-Ulrich
AU - Böhmer, Gerd
AU - Schmalfeldt, Barbara
AU - Wimberger, Pauline
AU - Beckmann, Matthias W
AU - Runnebaum, Ingo B
AU - Dürst, Matthias
PY - 2021/7/1
Y1 - 2021/7/1
N2 - PURPOSE: 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.METHODS: 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).RESULTS: 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.CONCLUSIONS: 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.
AB - PURPOSE: 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.METHODS: 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).RESULTS: 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.CONCLUSIONS: 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.
U2 - 10.3390/cancers13133309
DO - 10.3390/cancers13133309
M3 - SCORING: Journal article
C2 - 34282754
VL - 13
JO - CANCERS
JF - CANCERS
SN - 2072-6694
IS - 13
M1 - 3309
ER -