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

• Published in: Gynecologic oncology Vol. 151; no. 2; pp. 311 - 318
• Main Authors: Leeman, Annemiek, Ebisch, Renée M.F., Kasius, Annemieke, Bosgraaf, Remko P., Jenkins, David, van de Sandt, Miekel M., de Strooper, Lise M.A., Heideman, Daniëlle A.M., Snijders, Peter J.F., Massuger, Leon F.A.G., Bekkers, Ruud L.M., Meijer, Chris J.L.M., van Kemenade, Folkert J., Quint, Wim G.V., Melchers, Willem J.G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2018
• Subjects: Cervical cancer; Cervical intraepithelial neoplasia; Human papillomavirus; Methylation; Self-sampling; Triage; Self-sampling; Human papillomavirus; Triage; Methylation; Cervical intraepithelial neoplasia; Cervical cancer
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2018.09.006

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. 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. 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). 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. •Genotyping of self-samples finds the causative genotype of the worst underlying lesion in almost all HPV screen-positives.•Hypermethylation of FAM19A4/miR124-2 shows no difference between lesions caused by HPV16/18 or other hrHPV genotypes.•Our results support HPV16/18 genotyping and hypermethylation of FAM19A4/miR124-2 for triage of HPV self-screen-positives.