P16 expression in relation to human papillomavirus in liquid-based cervical smears

Area of Science:

• Gynecologic Oncology
• Virology
• Molecular Pathology

Background:

• Cervical cancer screening requires improved methods for detecting high-risk human papillomavirus (HPV) infections.
• p16 protein overexpression is associated with malignant cervical lesions and high-risk HPV.
• p16 is proposed as a surrogate marker for high-risk HPV in cervical cancer screening.

Purpose of the Study:

• To investigate the relationship between p16 expression and the physical status (integrated or episomal) of high-risk HPV DNA in liquid-based cervical smears.
• To evaluate the reliability of p16 as a surrogate marker for high-risk HPV infection in cervical screening.

Main Methods:

• Analysis of 241 liquid-based cervical smears using Pap test, in situ hybridization for HPV DNA, and immunocytochemistry for p16.
• Distinguishing between integrated (dotted signals) and episomal (diffuse signals) HPV DNA forms.

Main Results:

• High-grade intraepithelial lesions showed both integrated high-risk HPV and p16 overexpression.
• Some normal and ASCUS smears were p16-positive but HPV-negative.
• Episomal high-risk HPV was detected in some p16-negative ASCUS and low-grade intraepithelial lesions.

Conclusions:

• p16 alone is insufficient as a surrogate marker for high-risk HPV, as some infections may be missed.
• Missed high-risk HPV infections due to sole reliance on p16 could lead to delayed cancer progression management.
• A combined approach of HPV testing and p16 testing is recommended for improved triage of abnormal cervical smears.