Human papillomavirus, p16(INK4A), and Ki-67 in relation to clinicopathological variables and survival in primary carcinoma of the vagina

Br J Cancer. 2014 Mar 18;110(6):1561-70. doi: 10.1038/bjc.2014.32. Epub 2014 Feb 13.

Abstract

Background: This study aimed to determine human papillomavirus (HPV) status and to investigate p16(INK4A) and Ki-67 expression and their correlation with clinical parameters and survival in women with primary carcinoma of the vagina (PCV).

Methods: The presence of HPV DNA was evaluated by PCR. Genotyping was performed by Luminex in 68 short-term (2 years) and long-term (8 years) PCV survivors. p16(INK4A) and Ki-67 expression was evaluated by immunohistochemistry.

Results: Human papillomavirus DNA was detected in 43% of patients, the majority (63%) of whom were HPV16 positive. High p16(INK4A) expression was significantly correlated with low histopathological grade (P=0.004), HPV positivity (P=0.032), and long-term survival (P=0.045). High Ki-67 expression was negatively correlated with histopathological grade (P<0.001) and tumour size (P=0.047). There was an association between HPV positivity and low histopathological grade, but not between HPV positivity and survival.

Conclusion: High p16(INK4A) expression was associated with long-term survival, but the only independent predictors for survival were tumour size and histopathological grade. Our results indicate that p16(INK4A) and Ki-67 expression might be useful in tumour grading, and that it might be possible to use p16(INK4A) expression as a marker for HPV positivity, but this has to be further elucidated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cyclin-Dependent Kinase Inhibitor p16
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / biosynthesis*
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Prognosis
  • Survival Analysis
  • Vaginal Neoplasms / genetics
  • Vaginal Neoplasms / metabolism
  • Vaginal Neoplasms / pathology*
  • Vaginal Neoplasms / virology*

Substances

  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Ki-67 Antigen
  • Neoplasm Proteins