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.

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Keywords Cervical cancer, Cervical intraepithelial neoplasia, Human papillomavirus, Methylation, Self-sampling, Triage
Persistent URL dx.doi.org/10.1016/j.ygyno.2018.09.006, hdl.handle.net/1765/110308
Journal Gynecologic Oncology
Leeman, A. (Annemiek), Ebisch, R.M.F, Kasius, A. (Annemieke), Bosgraaf, R.P, Jenkins, D, van de Sandt, M.M, … Melchers, W.J. (2018). 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. Gynecologic Oncology. doi:10.1016/j.ygyno.2018.09.006