Diagnostic performance of HPV E6/E7 mRNA testing towards HPV-DNA testing and p16/Ki67 immunostaining as a biomarker of high-risk HPV recurrence in Greek women surgically treated for their cervical lesions

J Obstet Gynaecol Res. 2021 Oct;47(10):3607-3617. doi: 10.1111/jog.14976. Epub 2021 Aug 9.

Abstract

Aim: To evaluate the diagnostic performance of E6/E7 HPV-mRNA overexpression towards HPV-DNA testing and p16/Ki67 immunocytochemistry in a post-op population to verify if this biomarker can be effectively used as indicator of successful cervical intraepithelial neoplasia (CIN) treatment.

Methods: Our study retrospectively analyzed 197 patients of our Colposcopy Clinic between January 2013 and September 2020 coming with an abnormal Pap smear suggestive for colposcopy, and after a series of follow-ups including liquid-based cytology (LBC) and punch-biopsy sampling, there were surgically treated. LBC was used for cytology and molecular analysis of the three HPV-related biomarkers.

Results: Six months after treatment, 93% of the HPV-mRNA-positive women became negative while this applied to only 80.2% of the HPV-DNA-positive women. HPV persistence was 6.9% at 6-12 months after treatment. The comparison among cytology, colposcopy, HPV-DNA test, and HPV-mRNA test after treatment revealed that the last one is the only with a strong correlation with actual severity (histology during treatment) (ρ = 0.345, p = 0.006) implying that clinical cases with more severe CIN may have higher chances of unsuccessful treatment. HPV-mRNA test had higher sensitivity (100%), specificity (96.88%), and positive predictive value (45.45%) for CIN2+ recurrent lesions when compared with HPV-DNA testing (80%, 82.81%, 10.81% respectively) and p16/Ki67 immunocytochemistry (80%, 95.83%, 33.33% respectively) while their negative predictive values were similar.

Conclusions: E6/E7 mRNA detection has higher diagnostic values for the prediction of treatment failure compared with HPV-DNA testing and p16/Ki67 immunocytochemistry, and as an outcome could be used as predictive indicator of CIN-treatment status.

Keywords: CIN treatment; E6/E7 HPV-mRNA overexpression; HPV-mRNA testing; cervical cancer; post-op surveillance.

MeSH terms

  • DNA
  • Female
  • Greece
  • Humans
  • Ki-67 Antigen
  • Neoplasm Recurrence, Local
  • Oncogene Proteins, Viral*
  • Papillomaviridae / genetics
  • Papillomavirus Infections* / diagnosis
  • RNA, Messenger
  • Retrospective Studies
  • Sensitivity and Specificity
  • Uterine Cervical Neoplasms* / diagnosis
  • Uterine Cervical Neoplasms* / surgery

Substances

  • Ki-67 Antigen
  • Oncogene Proteins, Viral
  • RNA, Messenger
  • DNA