Correlation between high-risk HPV infection and p16/Ki-67 abnormalities in Pap samples in a South Eastern Europe cohort

J Med Virol. 2024 Mar;96(3):e29524. doi: 10.1002/jmv.29524.

Abstract

Cervical cancer (CC) is the fourth most common cause of cancer-related deaths amongst women worldwide. CC represents a major global healthcare issue, and Romania ranks the worst in mortality rates amongst EU countries. However, the early detection of CC can be lifesaving. To understand the testing process undergone by women in Romania, we performed a retrospective study, and investigated a cohort of 83 785 cervical cases from Romanian women aged 15-70, obtained in private-based opportunistic screening. We examined the correlation between Pap smear results, human papilloma virus (HPV) genotyping, and the expression of cell cycle markers p16 and Ki-67. Analysis of Pap results revealed approximately 10% abnormal cases, of which high-grade squamous intraepithelial lesions constituted 4.9%. HPV genotyping of 12 185 cases with available Pap results unveiled a range of high-risk HPV (hrHPV) types associated with cervical abnormalities. Notably, 26% of hrHPV-positive cases showed no observable abnormalities. In a subset of cases with abnormal Pap and a type of hrHPV, P16/Ki-67 double-staining was also positive. This study suggests the importance of an integrated diagnostic algorithm that should consider the HPV genotype, Pap smear, and p16/Ki-67 staining. This algorithm should enhance the CC screening accuracy and its management strategies, particularly in those regions with a high disease burden, such as Romania.

Keywords: HPV; Ki-67; Pap smear; cervical cancer; diagnostic algorithm; p16.

MeSH terms

  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Europe, Eastern
  • Female
  • Humans
  • Ki-67 Antigen / analysis
  • Ki-67 Antigen / metabolism
  • Papanicolaou Test / methods
  • Papillomaviridae / genetics
  • Papillomavirus Infections* / complications
  • Papillomavirus Infections* / diagnosis
  • Papillomavirus Infections* / epidemiology
  • Retrospective Studies
  • Uterine Cervical Dysplasia*
  • Uterine Cervical Neoplasms* / diagnosis
  • Uterine Cervical Neoplasms* / epidemiology
  • Uterine Cervical Neoplasms* / pathology
  • Vaginal Smears

Substances

  • Ki-67 Antigen
  • Cyclin-Dependent Kinase Inhibitor p16