Elevated Expression of Human Papillomavirus-16/18 E6 Oncoprotein Associates with Persistence of Viral Infection: A 3-Year Prospective Study in China

Cancer Epidemiol Biomarkers Prev. 2016 Jul;25(7):1167-74. doi: 10.1158/1055-9965.EPI-15-1057. Epub 2016 May 13.

Abstract

Background: An association between high-risk human papillomavirus (HR-HPV) oncoprotein expression and viral persistence has been suggested by the outcome of etiology studies, but there are no epidemiologic studies evaluating that link.

Methods: We performed a 3-year prospective study in which 2,498 Chinese women ages 25 to 65 years were screened by six screening tests, including the Onco E6: Cervical Test (Arbor Vita Corporation) in 2011 (baseline). Six-hundred and ninety women who were positive for any of the tests and a random sample of 164 women with all negative results received colposcopy, and cervical specimens for the cobas 4800 HPV test ("cobas," Roche Molecular Systems) were collected before colposcopy; of this group, 737 cervical specimens were collected to perform cobas and Onco E6: Cervical Test in 2014 (follow-up). Twenty-four cases of HPV16/18 E6 positives and 204 selected controls at baseline, 13 cases of HPV16/18 E6 positive and another 204 selected controls at follow-up were analyzed separately using unconditional logistical regression models to estimate ORs and 95% confidence intervals (CI).

Results: Compared with women who were HPV16 E6 oncoprotein negative at baseline, women in the E6-positive group had a much higher risk of HPV persistence (adjusted OR, 54.64; 95% CI, 7.19-415.09) at 3-year follow-up; a statistically strong association was also found between HPV16/18 HPV persistence and E6 oncoprotein expression detected at follow-up (adjusted OR, 360.57; 95% CI, 28.30-4,593.55).

Conclusions: A single detection of HPV16/18 E6 oncoprotein expression was strongly associated with viral persistence.

Impact: HPV16/18 E6 oncoprotein constitutes a marker for risk of HPV persistence. Cancer Epidemiol Biomarkers Prev; 25(7); 1167-74. ©2016 AACR.

MeSH terms

  • Adult
  • Aged
  • China / epidemiology
  • Colposcopy
  • Female
  • Human papillomavirus 16 / genetics*
  • Human papillomavirus 18 / genetics*
  • Humans
  • Mass Screening / methods*
  • Middle Aged
  • Oncogene Proteins, Viral / genetics*
  • Papillomavirus Infections / diagnostic imaging*
  • Papillomavirus Infections / epidemiology
  • Prospective Studies
  • Repressor Proteins / genetics*
  • Risk Factors
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / virology

Substances

  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Repressor Proteins