p16INK4A immunohistochemical staining and predictive value for progression of cervical intraepithelial neoplasia grade 1: A prospective study in China

p16^INK4A is strongly expressed in tissues diagnosed as cervical intraepithelial neoplasia (CIN) and cancer in women infected with human papillomavirus (HPV), but few prospective studies have evaluated p16^INK4A as a marker for the risk of low‐grade CIN (CIN1) progression. We investigated the prevalence of p16^INK4A immunostaining by CIN grade and whether overexpression of p16^INK4A in CIN1 predicts future risk for high‐grade CIN in Chinese women. 6,557 Chinese women aged 30–49 years were screened from 2003 to 2005 using cytology and carcinogenic HPV test. Colposcopy was performed on women with any abnormal result. p16^INK4A Immunostaining was performed on biopsies from all women with CIN1, as well as randomly selected women with normal or CIN grade 2 and worse (CIN2+) biopsies. Women with CIN1 were followed up without treatment. Colposcopy was performed on all untreated women at a 2‐year interval. The prevalence of p16^INK4A staining was 2.7%, 42.7%, 75.5%, 79.6% and 100% among women with normal, CIN1, 2, 3 and cancer biopsies, respectively (p < 0.001). HPV positivity was strongly associated with p16^INK4A staining odds ratios (OR) = 12.8; 95% confidence intervals (CI): 5.2–31.6]. p16^INK4A staining of CIN1 biopsies at baseline was associated with an increased risk of finding high‐grade CIN over 2 years of follow‐up (OR = 1.43; 95% CI: 0.52–3.91). The two‐year cumulative incidence of CIN2+ for p16^INK4A positive women was higher at 10.71% than for p16^INK4A negative women at 1.30% (crude RR = 8.25, 95% CI: 1.02–66.62). p16^INK4A overexpression is strongly associated with grade of CIN and risk of progression to high‐grade CIN in women with low‐grade lesions.