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

Abstract

Abstract. 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. IntroductionThe results of Pap tests performed during routine screenings at the beginning of prenatal care are abnormal in 8-12% of cases (1). Overall, the prevalence of abnormal cervical cytology in pregnancy is similar to that of age-matched, non-pregnant women (2). The incidence of cervical intraepithelial neoplasia (CIN) in pregnancy varies among different patient populations, as it does in non-pregnant women, but when age-matched, the risk of CIN is not higher than that among women who are not pregnant, ranging between 3.4 and 10.0% (3). The management of pregnant women with abnormal cytology depends on the degree of cytological abnormality, the outcome of colposcopy, and, when necessary, directed biopsy. Since, the only diagnosis that may alter management in pregnancy is invasive cancer, the management of pregnant women with abnormal cervical cytology or biopsy-proven CIN is generally more conservative compared with management of similar cytology and histology in non-pregnant women. However, management guidelines for cervical dysplasia are not well defined and are based on data collected from non-pregn...

Predictive Factors Involved in Postpartum Regressions of Cytological/Histological Cervical High-Grade Dysplasia Diagnosed during Pregnancy

“…Nonetheless, there is no consensus on the use of P16 and Ki67 during pregnancy, and the influences of hormones and immunity on these proteins remain unknown. The literature is scarce with only one study that has been published; furthermore, it was based on a small series of cases [26].…”

Disorders of the Cervix and Characteristics of Colposcopy in Pregnant Women

“…Однако при цитологическом исследовании распространенность LSIL составила 5,8%, HSIL -3,5% у пациенток с ВПЧ и 1,3% -без ВПЧ. По данным других авторов, аномальные результаты теста Папаниколау встречаются у беременных с частотой от 3,4% до 10% [7], HSIL -0,7% [8].…”

Cervical diseases in pregnant women. Socio-demographic and clinical-anamnestic risk factors

“…Полученные данные несколько отличаются от результатов, опубликованных другими авторами. Так, аномальные результаты цитологического исследования встречаются у беременных женщин с частотой от 3,4 и 10,0% и не отличаются от небеременных [4].…”