Risk stratification and long-term risk prediction of E6 oncoprotein in a prospective screening cohort in China

Int J Cancer. 2017 Sep 15;141(6):1110-1119. doi: 10.1002/ijc.30807. Epub 2017 Jun 21.

Abstract

E6 oncoprotein is a necessary agent of HPV driven oncogenic transformation. This study is aimed at evaluating the risk stratification potency of HPV 16/18 E6 oncoprotein (E6) as a triage method for HPV positivity. Moreover, it also acts as a predictor of cervical intraepithelial neoplasia grade 3 or worse (CIN3+). The screening cohort of 1,997 women was followed for a 15 year period in approximate five-year intervals. Participants were concurrently screened by HPV DNA testing (HC2), liquid based cytology (LBC), visual inspection with acetic acid (VIA) and were referred to colposcopy and biopsy if any tests reflected positive. E6 was performed on cervical samples collected from this cohort in 2005 and 2014. The ability of E6 to predict CIN3+ risk after the five- and ten-year interval was evaluated. Among HPV positive women in 2005, E6 indicated the lowest positive rate (9.9%) compared to LBC (48.4%) and VIA (28.0%), however, a higher prevalence rate (10.3%) and 10-year cumulative incidence rate (53.0%) of CIN3+ were detected among women who were E6 positive. Meanwhile, only 4.2% and 2.9% of women with abnormal LBC and positive VIA were diagnosed as prevalent CIN3+ in 2005, 23.0% and 16.5% developed to CIN3+ after year 10, respectively. Strong associations were found between precedent and subsequent HPV persistence and E6 oncoprotein expression (ORadjusted = 40.0 and 21.2, respectively). E6 oncoprotein could serve as a low-cost, highly specific, strongly indicative point-of-care method in the triage and treatment of HPV positive women.

Keywords: E6 oncoprotein; HPV; cervical cancer; risk predictor; screening cohort; triage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • China / epidemiology
  • Cohort Studies
  • DNA, Viral / analysis
  • DNA, Viral / genetics
  • DNA-Binding Proteins / analysis*
  • DNA-Binding Proteins / metabolism
  • Female
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / isolation & purification*
  • Human papillomavirus 16 / metabolism
  • Human papillomavirus 18 / genetics
  • Human papillomavirus 18 / isolation & purification*
  • Human papillomavirus 18 / metabolism
  • Humans
  • Middle Aged
  • Oncogene Proteins, Viral / analysis*
  • Oncogene Proteins, Viral / metabolism
  • Papillomavirus Infections / epidemiology
  • Papillomavirus Infections / metabolism*
  • Papillomavirus Infections / virology
  • Predictive Value of Tests
  • Prospective Studies
  • Repressor Proteins / analysis*
  • Repressor Proteins / metabolism
  • Risk Assessment
  • Uterine Cervical Dysplasia / epidemiology
  • Uterine Cervical Dysplasia / metabolism
  • Uterine Cervical Dysplasia / virology*
  • Uterine Cervical Neoplasms / epidemiology
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / virology*

Substances

  • DNA, Viral
  • DNA-Binding Proteins
  • E6 protein, Human papillomavirus type 16
  • E6 protein, Human papillomavirus type 18
  • Oncogene Proteins, Viral
  • Repressor Proteins