Human papillomavirus genotyping and p16INK4a expression in cervical intraepithelial neoplasia of adolescents

摘要

Adolescents have high rates of human papillomavirus (HPV) infection, and persistent high-risk HPV infection can lead to the development of cervical cancer. The cyclin-dependent kinase inhibitor, p16INK4a is overexpressed in cervical intraepithelial neoplasia (CIN), probably due to a persistent and integrated HPV infection. This study investigated p16INK4a expression, grades of CIN, and high-risk HPV infection in adolescent cervical biopsies. Biopsies were immunohistochemically stained for p16INK4a. The presence of wide-spectrum, low-risk, or high-risk HPV was determined by amplifying DNA extracted from the cervical biopsies. Biopsies were classified as cervicitis, 15 cases; CIN 1, 48 cases; CIN 2, 46 cases, and CIN 3, 52 cases. The distribution of p16INK4a staining was graded as patchy, diffuse basal, and diffuse full thickness. Pearson's 2 tests analyzed the relationships between p16INK4a staining, HPV infection, and CIN. Biopsies of cervicitis were negative for HPV and for p16INK4a expression. High-risk HPV 16, 18, and 31 increased from 18% in CIN 1 to 66% in CIN 2/3 (PINK4a was positive in 44% of biopsies with 35% showing patchy, 7% diffuse basal, and one case (2%) showing diffuse full thickness staining. In CIN 2/3, p16INK4a was positive in 97% of biopsies with 23% showing patchy, 21% diffuse basal, and 53% diffuse full thickness staining. The difference in the proportions of biopsies showing patchy p16INK4a staining in CIN 1 and diffuse full thickness staining in CIN 2/3 was significant (PINK4a negative, while all high-risk HPV-positive CIN 2/3 biopsies were p16INK4a positive. Diffuse, full thickness p16INK4a expression discriminated low-grade from high-grade CIN and appears to be a marker of persistent high-risk HPV infection.