Detection Of P16～(INK4A) Expression In Liquid-based Cervical Cytology

Aims: To assess the potential value of immunocytochemistry for P16^INK4A in liquid-based cervical cytology to help detect carcinoma cells and precursors in a screening setting and the use of P16^INK4A as a surrogate marker of human papillomavirus (HPV) infection. In order to offer an ecomomic valid method which can be used for clinical diagnosis and screening of precancerous and earlier carcinomas.Methods: 105 ThinPrep processed cervical cytology samples were studied: 10 cases negative for intraepithelial lesion or malignancy (NILM),25 Atypical squamous cell of undetermined significance(ASC-US),25 low grade squamous intraepithelial lesions (LSIL), 25 high grade squamous intraepithelial lesions (HSIL), 20 squamous cell carcinomas(SCC). The monoclonal antibodies were used to detect P16^INK4Aand HPV16/18-E6 , HPV 16,18DNA is detected by Fluorescence quantitative Polymerase Chain Reaction (FQ-PCR).Result: P16^INK4A immunoreactivity was shown in 0 of 10 (0%) of ThinPrep NILM samples, in 12 of 25 (48%) of ThinPrep ASC-US samples, in 16 of 25 (64%) of ThinPrep LSIL samples, in 21 of 25 (84%) of ThinPrep HSIL samples, in 19 of 20 (95%) of ThinPrep SCC samples. HPV16/18-E6 immunoreactivity was shown in 0 of 10 (0%) of ThinPrep NILM samples, in 4 of 25(16%) of ThinPrep ASC-US samples, in 9 of 25 (36%) of ThinPrep LSIL samples, in 12 of 25 (48%) of ThinPrep HSIL samples, in 11 of 20 (55%) of ThinPrep SCC samples. The expression rates of P16^INK4A was significantly higher following the development of cervical lesions(P<0.001). The expresion of HPV16,18DNA increases significantly following the development of cervical lesions(P<0.001). Close positive correlation was observed between the expression of P16^INK4A and HPV16,18DNA.Conclusion: P16^INK4A immunocytochemistry can be used as an adjunct to LBC in cervical screening,because it has a good disgnostic accuracy to discriminate HSIL and cervical cancer from other lesions. P16^INK4A expression was closely associated with high risk HPV infection It could be used as a surrogate marker of high-risk HPV infections. Combinations of dysplastic biomarkers may be useful in difficult diagnostic cases.