Utility of human papillomavirus L1 capsid protein and HPV test as prognostic markers for cervical intraepithelial neoplasia 2+ in women with persistent ASCUS /LSIL cervical cytology

Int J Med Sci. 2019 Aug 6;16(8):1096-1101. doi: 10.7150/ijms.31163. eCollection 2019.

Abstract

Objective: Efficient and highly predictive biomarkers reflecting the prognosis of persistent atypical squamous cells of unknown significance(ASCUS) and low grade squamous intraepithelial lesion(LSIL)s are unavailable and need to be developed urgently. We aimed to develop a predictive model for diagnosis of cervical intraepithelial neoplasia(CIN)2+ by analyzing the immunocytochemical expression of the HPV L1 capsid protein in patients with persistent ASCUS and LSIL with a high risk of HPV infection. Methods: Cervical cytology samples comprising (70 ASCUS and 215 LSIL Pap smears) were analyzed. Immunocytochemical identification of the HPV L1 capsid protein in cervical cytology samples was performed. Expression levels of HPV L1 capsid protein in cervical cytology samples were measured, and the correlation between HPV L1 expression and cervical pathologic diagnosis was evaluated. The risk for CIN2+ was calculated using the results of immunocytochemistry and the HPV DNA test. Results: Negative results for HPV L1 immunochemistry test were more frequently observed in CIN2+, and expression of the HPV L1 capsid protein was higher in CIN1 or cervicitis (Fisher's exact test, p<0.05). Diagnosis rates for CIN2+ were highest for the combination of HPV L1 capsid protein immunocytochemistry, cytology and HPV test when compared with other combinations (Akaike information criterion (AIC): 191.7, Schwarz criterion(SC): 206.3, p<0.001). Conclusion: Absence of HPV L1 capsid expression and presence of HPV type 16 or 18 infection are reliable predictors of progression to CIN2+ in patients showing persistent ASCUS and LSIL.

Keywords: Atypical squamous cells of unknown significance; Cervical Intraepithelial Neoplasia; Human papillomavirus 16; Human papillomavirus 18; Low grade squamous intraepithelial lesion.

MeSH terms

  • Adult
  • Aged
  • Atypical Squamous Cells of the Cervix / metabolism
  • Atypical Squamous Cells of the Cervix / pathology
  • Atypical Squamous Cells of the Cervix / virology*
  • Biomarkers, Tumor / analysis*
  • Capsid Proteins / analysis*
  • Capsid Proteins / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Oncogene Proteins, Viral / analysis*
  • Oncogene Proteins, Viral / metabolism
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / pathology*
  • Papillomavirus Infections / virology
  • Prognosis
  • Uterine Cervical Dysplasia / metabolism
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / virology*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology*
  • Vaginal Smears
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Capsid Proteins
  • HPV L1 protein, Human papillomavirus
  • Oncogene Proteins, Viral