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Br J Cancer. 2016 Aug 23;115(5):579-87. doi: 10.1038/bjc.2016.200. Epub 2016 Jul 14.

FAM19A4 methylation analysis in self-samples compared with cervical scrapes for detecting cervical (pre)cancer in HPV-positive women.

Author information

1
Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
2
Department of Obstetrics and Gynaecology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
3
Department of Epidemiology and Biostatistics, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
4
Department of Pathology, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
5
Department of Obstetrics and Gynaecology, Erasmus MC University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
6
UMC Utrecht Cancer Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
7
Roosevelt Clinic, Rooseveltstraat 67, 2321 CT Leiden, The Netherlands.
8
Department of Obstetrics and Gynaecology, Flevo Hospital, Hospitaalweg 1, 1315 RA Almere, The Netherlands.
9
Department of Obstetrics and Gynaecology, Sint Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, The Netherlands.
10
DDL Diagnostic Laboratory, Visseringlaan 25, 2288 ER Rijswijk, The Netherlands.
11
Department of Obstetrics and Gynaecology, Onze Lieve Vrouwe Gasthuis West, Oosterpark 9, 1091 AC Amsterdam, The Netherlands.

Abstract

BACKGROUND:

High-risk human papillomavirus (hrHPV)-positive women require triage to identify those with cervical high-grade intraepithelial neoplasia and cancer (⩾CIN3 (cervical intraepithelial neoplasia grade 3)). FAM19A4 methylation analysis, which detects advanced CIN and cancer, is applicable to different sample types. However, studies comparing the performance of FAM19A4 methylation analysis in hrHPV-positive self-samples and paired physician-taken scrapes are lacking.

METHODS:

We compared the performance of FAM19A4 methylation analysis (and/or HPV16/18 genotyping) in self-samples and paired physician-taken scrapes for ⩾CIN3 detection in hrHPV-positive women (n=450,18-66 years).

RESULTS:

Overall FAM19A4 methylation levels between sample types were significantly correlated, with strongest correlation in women with ⩾CIN3 (Spearman's ρ 0.697, P<0.001). The performance of FAM19A4 methylation analysis and/or HPV16/18 genotyping did not differ significantly between sample types. In women ⩾30 years, ⩾CIN3 sensitivity of FAM19A4 methylation analysis was 78.4% in self-samples and 88.2% in scrapes (ratio 0.89; CI: 0.75-1.05). In women <30 years, ⩾CIN3 sensitivities were 37.5% and 45.8%, respectively (ratio 0.82; CI: 0.55-1.21). In both groups, ⩾CIN3 specificity of FAM19A4 methylation analysis was significantly higher in self-samples compared with scrapes.

CONCLUSIONS:

FAM19A4 methylation analysis in hrHPV-positive self-samples had a slightly lower sensitivity and a higher specificity for ⩾CIN3 compared with paired physician-taken scrapes. With a similarly good clinical performance in both sample types, combined FAM19A4 methylation analysis and HPV16/18 genotyping provides a feasible triage strategy for hrHPV-positive women, with direct applicability on self-samples.

PMID:
27415009
PMCID:
PMC4997542
DOI:
10.1038/bjc.2016.200
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

JB has played an advisory role for Merck and Roche, has been on the speakers bureau of Qiagen and has received a travel reimbursement from DDL Diagnostic Laboratory. PJFS has been on the speakers bureau of Roche, Qiagen, Abbott, Gen-Probe and Seegene. PJFS is consultant for Crucell Holland BV. TJMH, RHMV and WAH have been principal investigators of a GlaxoSmithKline sponsored study. WGVQ is a minority shareholder of Diassay BV and obtained grants from GlaxoSmithKline. DAMH has been on the speakers bureau of Hologic/Gen-Probe and serves occasionally on the scientific advisory boards of AMGEN and Pfizer. CJLMM has been on the sponsored speakers bureau of GlaxoSmithKline, Qiagen, Merck, Roche, Menarini and Segeene, and served on the scientific advisory board of GlaxoSmithKline, Qiagen, Merck and Roche. CJLMM has been consultant for Qiagen and Genticel and is a minority shareholder of Diassay BV. Formerly, CJLMM was a minority shareholder of Delphi Biosciences. CJLMM, PJFS, RDMS and DAMH have minority stake in Self-screen BV, a spin-off company of VU University Medical Center Amsterdam, which holds patents related to the present work. RL, LMADS, MGD, FJvK, LR, WMvB, GCMG, JWMS and DKEvD do not have any conflict of interest to declare.

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