Format

Send to

Choose Destination
Gynecol Oncol. 2018 Nov;151(2):311-318. doi: 10.1016/j.ygyno.2018.09.006. Epub 2018 Sep 13.

Defining hrHPV genotypes in cervical intraepithelial neoplasia by laser capture microdissection supports reflex triage of self-samples using HPV16/18 and FAM19A4/miR124-2 methylation.

Author information

1
DDL Diagnostic Laboratory, Rijswijk, the Netherlands.
2
Department of Obstetrics and Gynaecology, Radboud university medical center, Nijmegen, the Netherlands.
3
Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam, the Netherlands.
4
Department of Obstetrics and Gynaecology, Radboud university medical center, Nijmegen, the Netherlands; Department of Obstetrics and Gynaecology, Catharina Hospital, Eindhoven, the Netherlands.
5
Erasmus Medical Center, Department of Pathology, Rotterdam, the Netherlands.
6
DDL Diagnostic Laboratory, Rijswijk, the Netherlands. Electronic address: wim.quint@ddl.nl.
7
Department of Medical Microbiology, Radboud university medical center, Nijmegen, the Netherlands.

Abstract

OBJECTIVE:

HPV16/18 genotyping and detection of hypermethylation of human cell genes involved in cervical oncogenesis have shown promising results in triage of high-risk HPV (hrHPV)-screen positive women on cervical smears. These tests can be performed on self-samples, which contain cervical and vaginal cells. We studied whether a self-sample represents the hrHPV type causing the worst cervical lesion and whether any differences in hypermethylation of FAM19A4/miR124-2 exist between CIN lesions caused by different hrHPV types. These results have important implications for reflex triage of self-samples.

METHODS:

Correlation between genotype found on self-sample using GP5+/6+-PCR-EIA-LMNX and causative hrHPV genotype in the worst lesion on histology was studied using laser capture microdissection (LCM)-SPF10-PCR (N = 152). Hypermethylation of FAM19A4/miR124-2 in the self-sample was tested in a quantitative methylation specific PCR and compared between lesions caused by HPV16/18 and other hrHPV genotypes.

RESULTS:

Causative hrHPV genotype of the worst lesion (CIN1, CIN2, CIN3, invasive cervical cancer) was detected on self-sample in 93.4%. HPV16 was the most frequently found genotype on self-sampling (39.2%, 73/186) and causative genotype in CIN3+ (51.4%, 38/74, all detected on self-sample). There were no differences in the percentages of positive FAM19A4/miR124-2 methylation assays between lesions caused by HPV16/18 (73.8% in CIN3+) or other hrHPV genotypes (66.7% in CIN3+) (p = 0.538).

CONCLUSIONS:

Our results show that hrHPV genotypes found on self-sample were a good representation of hrHPV in the worst CIN lesion and that methylation testing on self-sample for detection of CIN3+ was not significantly different between lesions caused by HPV16/18 and other hrHPV genotypes.

KEYWORDS:

Cervical cancer; Cervical intraepithelial neoplasia; Human papillomavirus; Methylation; Self-sampling; Triage

PMID:
30219239
DOI:
10.1016/j.ygyno.2018.09.006
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center