Cervical intraepithelial neoplasia in pregnancy: Interference of pregnancy status with p16 and Ki-67 protein expression

Andrea Ciavattini, Francesco Sopracordevole, Jacopo Di Giuseppe, Lorenzo Moriconi, Guendalina Lucarini, Francesca Mancioli, Antonio Zizzi, Gaia Goteri

Research output: Contribution to journalArticlepeer-review


To date, there are evidence-based guidelines available for cervical dysplasia diagnosed in pregnancy. Certain functional biomarkers have proven useful in the prediction of regressing and non-regressing cervical intraepithelial neoplasia (CIN) lesions in non-pregnant women. In the present study, Ki-67 and p16 immunostaining were evaluated in different grades of CIN lesions diagnosed in pregnant or non-pregnant women with the aim to identify any differences in order to better understand the behavior of CIN in pregnancy. The current retrospective case-control study included 17 pregnant patients that conceived naturally with first-time onset of CIN occurring at no later than 16 gestational weeks. The control group included 17 non-pregnant patients matched for age, parity and number of previous sexual partners. Exclusion criteria included previous cervical treatment, immunocompromised status, chronic hepatitis B and/or C and cigarette smoking. p16 and Ki-67 protein expression were respectively detected using the CINtec Histology kit and monoclonal antibodies against Ki-67. p16 and Ki-67 staining were analyzed using a classification system based on the distribution of positivity on a semi-quantitative three point-scale. p16 and Ki-67 immune reactivity correlated positively with the grade of epithelial dysplasia in the total cohort of pregnant and non-pregnant patients; expression increased linearly from CIN1 to CIN3. Furthermore, the association between p16 immunostaining and CIN grade was significant in non-pregnant patients but not in pregnant patients. In pregnant patients, positivity for Ki-67 was less intense than in non-pregnant patients. These results appear to suggest that pregnancy status interferes with the expression of cellular proteins involved in cell-cycle regulation and the carcinogenic process induced by high-risk human papilloma virus, exhibiting increased variability in their staining.

Original languageEnglish
Pages (from-to)301-306
Number of pages6
JournalOncology Letters
Issue number1
Publication statusPublished - Jan 1 2017


  • Cervical intraepithelial neoplasia
  • Human papilloma virus
  • Ki-67 antigen
  • P16
  • Pregnancy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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