Evaluation of Integrated HPV DNA as Individualized Biomarkers for the Detection of Recurrent CIN2/3 during Post-Treatment Surveillance.
CIN3
HPV DNA integration
individualized molecular biomarker
post treatment surveillance
recurrence
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
01 Jul 2021
01 Jul 2021
Historique:
received:
07
05
2021
revised:
11
06
2021
accepted:
28
06
2021
entrez:
20
7
2021
pubmed:
21
7
2021
medline:
21
7
2021
Statut:
epublish
Résumé
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 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.
Identifiants
pubmed: 34282754
pii: cancers13133309
doi: 10.3390/cancers13133309
pmc: PMC8269020
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Bundesministerium für Bildung und Forschung
ID : 13GW0221A and 13GW0221B
Références
Am J Obstet Gynecol. 2010 Jul;203(1):72.e1-6
pubmed: 20417477
Gynecol Oncol. 2012 May;125(2):500-7
pubmed: 22266548
J Clin Microbiol. 1997 Mar;35(3):791-5
pubmed: 9041439
Int J Cancer. 2012 Sep 1;131(5):E593-602
pubmed: 22262398
Medicine (Baltimore). 2018 Jan;97(4):e9719
pubmed: 29369205
Aust Fam Physician. 2015 Jan-Feb;44(1-2):64-8
pubmed: 25688965
Obstet Gynecol. 2013 Apr;121(4):829-846
pubmed: 23635684
Genome Res. 2014 Feb;24(2):185-99
pubmed: 24201445
Sci Rep. 2016 Oct 19;6:35427
pubmed: 27759101
Int J Mol Sci. 2017 Sep 22;18(10):
pubmed: 28937589
Nat Genet. 2015 Feb;47(2):158-63
pubmed: 25581428
Proc Natl Acad Sci U S A. 1987 Feb;84(4):1070-4
pubmed: 3029760
PLoS One. 2012;7(6):e39632
pubmed: 22761851
Gynecol Oncol. 2016 Oct;143(1):135-142
pubmed: 27430395
Diagn Cytopathol. 2020 Jul;48(7):635-644
pubmed: 32275355
Int J Cancer. 2001 Apr 1;92(1):9-17
pubmed: 11279600
Int J Cancer. 2017 Jan 15;140(2):423-430
pubmed: 27677098
Lancet Oncol. 2007 Nov;8(11):985-93
pubmed: 17928267
Vaccine. 2006 Aug 31;24 Suppl 3:S3/78-89
pubmed: 16950021
Eur J Obstet Gynecol Reprod Biol. 2020 May;248:44-49
pubmed: 32172024
J Gen Virol. 1985 Jul;66 ( Pt 7):1515-22
pubmed: 2991428
Virol J. 2019 Nov 27;16(1):148
pubmed: 31775792
PLoS One. 2013 Jun 18;8(6):e66693
pubmed: 23824673
BJOG. 2018 Jan;125(1):74-79
pubmed: 28678394
Stat Med. 1998 Apr 30;17(8):857-72
pubmed: 9595616
Nat Rev Cancer. 2007 Jan;7(1):11-22
pubmed: 17186016
Nat Genet. 2016 Jan;48(1):2-4
pubmed: 26711106
Stat Med. 2002 Mar 30;21(6):835-52
pubmed: 11870820
BMJ. 2006 May 6;332(7549):1089-92
pubmed: 16675820
Cancer Res. 2008 Apr 1;68(7):2514-22
pubmed: 18381461
Geburtshilfe Frauenheilkd. 2017 Aug;77(8):887-893
pubmed: 28845053