In Honduras, premalignant and malignant lesions of the cervix continues to represent a major burden on the health care system mainly due to decreased specificity of screening tests as well as significant interobserver variability in the diagnosis of these lesions. Since p16INK4a is a surrogate marker of HPV E7-mediated pRb catabolism, it has been successfully deployed for the classification of HPV-related disease. This study aimed to assess the clinical significance of overexpression of p16INK4a in cervical lesions.
To help delineate the utility of p16INK4a, colposcopy-directed biopsy samples drawn from a larger study (n = 20: negative, 9; CIN I, 3; CIN II, 8) were analyzed by immunohistochemistry for expression of p16INK4a. Testing for high-risk human papillomavirus types by Hybrid Capture2 and genotyping by L1 HPV region PCR (GP5/6+) followed by reverse hybridization (LiPA) was performed on concurrent cervical scrape specimens.
None of the negative and CIN I cases (n=12) expressed the p16INK4a protein. On the other hand, all CIN II specimens (n=8) were positively associated with p16INK4a expression and high-risk HPV presence (P < .001), showing a sensitivity and specificity of 100% (95% CI: 75.7-100.0). The HPV prevalence in the negative and CIN I cases was 50% as opposed to 100% of CIN II cases. The viral types identified in the CIN II cases were 16, 18, 35, 58, 51 and 66, being HPV16 the most common.
Although a small sample size, our findings show a possible utility for adjunct p16 INK4a in addition to HR- HPV testing to distinguish between negative/low-grade (CIN 1) and high-grade squamous intraepithelial lesions (CIN II+) to avoid overtreatment of false-positive cases and under treatment of false-negative cases. It is suggested to test a larger sample size to increase the statistical significance of the study.