Detection of HPV E6 oncoprotein from urine via a novel immunochromatographic assay

PLoS One. 2020 Apr 22;15(4):e0232105. doi: 10.1371/journal.pone.0232105. eCollection 2020.

Abstract

Cervical cancer is a significant public health problem, especially in low- and middle-income countries, where women have little access to cervical cancer screening; consequently 80% of cervical cancer related mortality occurs in these regions. The development of screening methods that need less infrastructure thus represents an urgent medical need. The study aims to compare the detection rates of high-risk human papillomavirus 16 and 18 E6 oncoprotein in urine, vaginal self-collected, and cervical scrapes of women using the OncoE6™ Cervical Test and compare the HPV16 and/or HPV18 E6 detection rates with the HPV DNA testing. Paired urine, vaginal self-collected and cervical specimens were collected from 124 women who participated in cervical cancer screening or treatment in this proof-of-concept study and underwent to HPV16/18-E6 testing and high-risk HPV DNA testing prior to treatment of cervical neoplasia or cancer. Concordance between urinary, vaginal and cervical HPV16/18-E6 and HPV-DNA testing was evaluated for patients classified as negative group (<CIN2) and histological positive group (CIN2, CIN3 and invasive carcinoma). Overall, HPV16/18-E6 oncoprotein was detected in 30.6% of cervical samples, 20.3% of self-collected vaginal samples and 21% of urine samples. Regarding the clinical sensitivity, the HPV16/18-E6 oncoprotein was not detected in CIN2 cases, and was detected at low rates in CIN3 cases. The clinical sensitivity of the HPV16/18-E6 oncoprotein for detecting invasive cervical cancer was 70% for cervical scrapes, 55% for self-collected vaginal samples and 52% for urine samples. This study reports the urinary detection of E6 oncoprotein in vivo for the first time and our results suggest that this detection is only for invasive/microinvasive lesions. Then, further protocol development and standardization to achieve a clinical sensitivity for CIN2/3 detection close to what can be achieved for invasive lesions using the physician collected cervical is needed.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / urine*
  • Female
  • Human Papillomavirus DNA Tests
  • Human papillomavirus 16 / genetics
  • Humans
  • Immunoassay / methods*
  • Middle Aged
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / urine*
  • Papillomavirus Infections / virology
  • Repressor Proteins / genetics
  • Repressor Proteins / urine*
  • Uterine Cervical Neoplasms / virology
  • Vagina / virology

Substances

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

Grant support

This study was supported by Bill and Melinda Gates Foundation OPP1151345 and FAPESP 2016/19527-7. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Arbor Vita Corporation provided support donating the OncoE6 Cervical Test kits and in the form of salaries for authors [JS and MB], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.