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Human papillomavirus type 16 L1/L2 DNA methylation shows weak association with cervical disease grade in young women

Bryant, Dean, Hibbitts, Samantha Jayne, Almonte, Maribel, Tristram, Amanda Jane, Fiander, Alison Nina and Powell, Ned George 2015. Human papillomavirus type 16 L1/L2 DNA methylation shows weak association with cervical disease grade in young women. Journal of Clinical Virology 66 , pp. 66-71. 10.1016/j.jcv.2015.03.001

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Background Persistent infection with human papillomavirus (HPV) type 16 causes the majority of cervical cancers. Genital HPV infection is very common, but neoplastic progression is uncommon. There is an urgent need for biomarkers associated with cervical neoplasia, to enable triage of women who test positive for HPV. Objectives To assess the ability of quantitative measurement of HPV16 DNA methylation to separate samples of different cytological and histological grades from young women, among whom rates of HPV infection are high. Study design DNA methylation was quantified by pyrosequencing of bisulphite converted DNA from liquid based cytology samples from 234 women (mean age 20.6 years) who tested positive for HPV16 and showed varying degrees of neoplasia. Methylation was assessed at CpGs in the HPV E2 and L1/L2 regions. Results The performance of methylation-based classifiers was assessed by ROC curve analyses. The best combination of CpGs (5600 and 5609) achieved AUCs of 0.656 (95% CI = 0.520–0.792) for separation of cytologically normal and severely dyskaryotic samples, and 0.639 (95% CI = 0.547–0.731) for separation of samples with or without high-grade neoplasia (CIN2+/−). Conclusions The data are consistent with HPV L1/L2 methylation being a marker of the duration of infection in a specific host. Assessment of HPV DNA methylation is hence a promising biomarker to triage HPV-positive cytology samples, but may have limited utility in young women. Future studies assessing the likely utility of HPV DNA methylation as a potential triage biomarker must take account of women’s age.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Human papillomavirus; HPV; Cervical; Methylation; Young women; Screening
Publisher: Elsevier
ISSN: 1386-6532
Date of Acceptance: 3 March 2015
Last Modified: 31 Jan 2020 06:49

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