Follow-up of high-risk HPV positive women by combined cytology and bi-marker CADM1/MAL methylation analysis on cervical scrapes.

Autor: Verhoef VM; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands., van Kemenade FJ; Department of Pathology, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Rozendaal L; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands., Heideman DA; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands., Bosgraaf RP; Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands., Hesselink AT; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands., Melchers WJ; Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands., Massuger LF; Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands., Bekkers RL; Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands., Steenbergen RD; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands., Berkhof J; Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands., Snijders PJ; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands., Meijer CJ; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: cjlm.meijer@vumc.nl.
Jazyk: angličtina
Zdroj: Gynecologic oncology [Gynecol Oncol] 2015 Apr; Vol. 137 (1), pp. 55-9. Date of Electronic Publication: 2015 Feb 08.
DOI: 10.1016/j.ygyno.2015.01.550
Abstrakt: Objectives: Triage of HPV screen-positive women is needed to identify those with underlying cervical intraepithelial neoplasia grade 2/3 or worse (CIN2/3+). Presently, cytology on a physician-taken cervical scrape is mostly accepted as triage test, but needs follow-up testing in order not to miss severe disease. Here, we evaluated the performance of combined cytology and bi-marker CADM1/MAL-methylation analysis as triage test on physician-taken cervical scrapes of HPV positive women.
Methods: In this post-hoc analysis, we used 364 left-over HPV positive cytology triage samples of participants of a randomized controlled trial (PROHTECT-3: n=46,001) performed in population-based cervical screening. Study endpoints were CIN2+ and CIN3+ detection. Cytology testing with and without methylation marker analysis was evaluated with regard to sensitivity, specificity, positive and negative predictive value, and referral rate.
Results: Bi-marker CADM1/MAL-methylation positivity increased proportionally with severity of underlying lesions. Overall, cytology and bi-marker CADM1/MAL-methylation analysis yielded similar performances with regard to CIN3+ detection, yet in combination a significantly higher sensitivity for CIN3+ (88.7%) was obtained at a specificity of 53.6% and a colposcopy referral rate of 53.6%. The combined strategy detected all six cervical cancers, whereas triage by cytology alone failed to detect two of them.
Conclusions: Cytology and bi-marker CADM1/MAL-methylation analysis perform complementary for CIN2+/CIN3+ detection when used as triage tool on cervical scrapes of HPV positive women. This approach not only results in a higher CIN3+ sensitivity than cytology triage with an acceptable referral rate, but also seems to reduce the risk of missing cervical cancers and advanced high-grade lesions.
(Copyright © 2015 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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