P16INK4a: a potential diagnostic adjunct for prediction of high-grade cervical lesions in liquid-based cytology: with HPV testing and histological correlation.

Human papillomavirus (HPV) is a necessary cause of cervical cancer and its precursors. Increased expression of high-risk hrHPV viral oncogenes in abnormal cells might increase the expression of p16INK4a. We aimed to determine the role of p16INK4a in detecting hrHPV-transformed epithelial cells in liquid-based cervical cytology, and compared the results with hrHPV DNA testing by realtime polymerase chain reaction (RT-PCR). Fifty-seven cytological samples were tested for p16INK4a immunomarker and hrHPV DNA. Test performance of both tests was determined by comparing sensitivity, specificity and predictive values using available histological follow-up data as gold standard. Of 57 samples, 36 (63.2%) showed immunoreactivity for p16INK4a and 43 (75.4%) were hrHPV-infected. A fairly low concordance rate (k = 0.504) between p16INK4a immunolabelling and hrHPV DNA status was noted. For prediction of cervical intraepithelial neoplasia (CIN) II and worse lesions, p16INK4a had a sensitivity and specificity of 93.5% and 60%; whereas hrHPV DNA testing had a sensitivity and specificity of 100% and 20%. Dual testing by combining p16INK4a and hrHPV showed sensitivity and specificity of 100% and 33.3%. In conclusion, p16INK4a is useful in predicting severity of the cytological abnormalities. Although p16INK4a is more specific but less sensitive than hrHPV in detecting high-grade cervical lesions, a combination of both tests failed to demonstrate significant improvement in diagnostic sensitivity, specificity and predictive value. Larger-scale prospective studies are required to assess further whether this biomarker should be routinely used as primary screening tool independently or in combination with hrHPV testing to improve diagnostic accuracy in cervical cytology.

Mucosal cytokine production in radiation-induced proctosigmoiditis compared with inflammatory bowel disease.

OBJECTIVE: We measured the mucosal levels of interleukin 1beta (IL-1beta), IL-2, IL-6, and IL-8 in affected segments of radiation-induced proctosigmoiditis and compared these with the levels in normal controls and inflammatory bowel disease (IBD) patients. METHODS: Thirteen patients with histologically proven radiation proctosigmoiditis, 32 patients with active ulcerative colitis (UC), 35 patients with Crohn's disease, and 15 normal subjects undergoing routine colonoscopy were included in the study. All patients underwent colonoscopy and mucosal biopsies were obtained from both diseased and normal-appearing areas. Mucosal levels of IL-1beta, IL-2, IL-6, and IL-8 were determined by solid-phase enzyme-linked immunosorbent assay (ELISA) using the Quantikine method (R&D Systems, Minneapolis, MN). All the data were statistically analyzed using Student's t test. RESULTS: The mucosal levels of IL-2, IL-6, and IL-8 were significantly higher in both diseased segments (5.62 +/- 0.13, 1.60 +/- 0.31, and 21.45 +/- 4.03 pg/ml, respectively) and normal-appearing segments (3.83 +/- 0.78, 1.36 +/- 0.34, and 13.45 +/- 3.18 pg/mg) in the radiation proctitis group compared to those of normal control subjects (1.74 +/- 0.23, 0.67 +/- 0.09, and 4.99 +/- 1.39 pg/mg). These differences were statistically significant (p < 0.05). In the UC group, IL-1beta, IL-6, and IL-8 levels in diseased segments were 4.98 +/- 0.53, 2.22 +/- 0.28, and 88.85 +/- 8.05 pg/mg, respectively. In Crohn's disease patients, IL-1beta, IL-6, and IL-8 levels were 5.45 +/- 0.93, 2.88 +/- 0.58, and 61.68 +/- 10.02 pg/mg, respectively. All these levels were significantly higher (p < 0.05) compared with IL-1beta, IL-6, and IL-8 levels from normal segments of IBD patients. Compared with the radiation proctitis patients, the levels of IL-6 and IL-8 were significantly higher in the IBD group. CONCLUSIONS: The mucosal levels of IL-2, IL-6, and IL-8 were significantly higher in both diseased and normal segments of colon in patients with radiation proctitis, compared with normal controls. Only IL-1beta levels were significantly higher in diseased segments, compared with endoscopically normal-appearing segments in radiation proctitis. These results indicate that there is a similarity in the activation of mucosal cytokines between IBD and radiation proctosigmoiditis. This may partly explain the beneficial effects of similar topical and systemic agents such as steroids and mesalamine compounds when used in radiation-induced proctosigmoiditis.