Transition of cervical carcinoma in situ to invasive cancer: Role of p16INK4a expression in progression and in recurrence

To investigate the expression of p16INK4a in cervical carcinoma and its relation to the transition of carcinoma in situ to invasive carcinoma, and its role in recurrence of cervical lesions as well, a series of 90 patients with cervical carcinoma (49 with in situ lesion and 41 with invasive lesion) were selected from July 2001 and September 2002. Groups with in situ and invasive lesions were paired for a series of risk variables for cervical cancer and followed up for 60 months. The follow-up visits occurred every 6 months in the first three years and annually up to the fifth year. It was observed that 87.9% of the patients with invasive lesion showed overexpression of p16INK4a, in comparison with 37.6% of those with in situ lesion (X2: 13.68; 2 df; p = 0.0002; OR: 12.08), demonstrating overexpression of p16INK4a as a risk of invasion of the basal layer by dysplastic cells. We also observed an association between overexpression of p16INK4a and staging of cancer (X2: 18.38; 6 df; p = 0.0003). A prospective analysis, when controlled for interaction with cervical lesion groups (by Cox regression), demonstrated a risk of recurrence of 4.83 times attributed to overexpression of p16INK4a, albeit not statistically significant (p = 0.14).