title: Human papillomavirus type 16 L1/L2 DNA methylation shows weak association with cervical disease grade in young women.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
authors: School of Medicine, Heath Park, Cardiff University, CF64 3RL, UK. Electronic address: dean.bryant@gmail.com.
authors: Dean
authors: D
authors: Bryant
authors: School of Medicine, Heath Park, Cardiff University, CF64 3RL, UK. Electronic address: hibbittssj@cf.ac.uk.
authors: Samantha
authors: S
authors: Hibbitts
authors: Prevention and Implementation Group, IARC, Lyon CEDEX 08, France. Electronic address: almonteM@iarc.fr.
authors: Maribel
authors: M
authors: Almonte
authors: School of Medicine, Heath Park, Cardiff University, CF64 3RL, UK. Electronic address: tristramaj@cf.ac.uk.
authors: Amanda
authors: A
authors: Tristram
authors: School of Medicine, Heath Park, Cardiff University, CF64 3RL, UK. Electronic address: fianderan@cf.ac.uk.
authors: Alison
authors: A
authors: Fiander
authors: School of Medicine, Heath Park, Cardiff University, CF64 3RL, UK. Electronic address: powellng@cf.ac.uk.
authors: Ned
authors: N
authors: Powell
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D036022:Capsid Proteins / Q000235:genetics*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D030361:Papillomavirus Infections / Q000150:complications / Q000473:pathology* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000821:virology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D036022:Capsid Proteins; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; C063317:L1 protein, Human papillomavirus type 16
keywords: Cervical; HPV; Human papillomavirus; Methylation; Screening; Young women