P16半定量评分在宫颈上皮内瘤变诊断中的应用及与人乳头瘤病毒亚型感染的关系

摘要

目的 探讨P16免疫组织化学半定量评分在宫颈上皮内瘤变(CIN)进行分级诊断中的作用及意义;分析P16表达情况、人乳头瘤病毒(HPV)感染及亚型分布的关系.方法 ①运用免疫组织化学二步法对P16进行蛋白染色,半定量评分.②采用聚合酶链反应+膜杂交法同时检测常见21种HPV亚型.结果 P16阳性率随宫颈病变级别的升高而增强,两者密切相关(P<0.01),组间差异均具有统计学意义(P<0.01),对CIN病变的预测灵敏度高,特异性强.免疫组织化学半定量评分结果显示:P16在表达炎症组中为阴性,CINⅠ级多数表达为+和++;CINⅡ级多为++和+++;CINⅡ~Ⅲ级表达为+++;CINⅢ级为+++和++++.HPV总感染率为73.62%,随宫颈病变级别升高阳性率增高,HPV16型感染与宫颈CIN二级分类病变程度有统计学意义(P=0.002).随P16表达强度升高,HPV感染率随之增高.且HPV16型、58型、52型、31型、66型和高危混合型在P16阴性和阳性比较中差异有统计学意义(P<0.05).结论 P16免疫组织化学半定量评分能够客观地反映CIN病变的程度,P16检测对宫颈CIN病变合并HPV感染病例预后及转归具有一定的提示.%Objective To investigate the effect and significance of P16 semi-quantitative immunohistochemical score for the classification of cervical intraepithelial neoplasia (CIN), and to analyze the correlations among the expres-sion of P16 protein, human papillomavirus (HPV) infection and the distribution of HPV subtypes. Methods ①Protein P16 was determined by two-step immunohistochemical staining, and the semi-quantitative immunohistochemical score was obtained. ②Twenty-one common HPV subtypes were determined by PCR and membrane hybridization. Results The P16 positive rate increased along with higher level of cervical lesion, with significant correlation ( P<0.01), and statistical significance (P<0.01) between them, which had high sensitivity for the prognosis of CIN lesions, and strong specificity. The immunohistochemical semi-quantitative score showed that the expression of P16 was negative in the inflammation group, (100%). The expressions of CIN Ⅰ, CINⅡ, CINⅡ-Ⅲand CINⅢlevels were+and++, ++and+++, +++, and +++ and ++++, respectively. The total infection rate of HPV was 73.62%. The P16 positive rate in-creased along with higher level of cervical lesion. There was statistical significance between HPV16 infection and sec-ondary classification of cervical CIN lesions (P=0.002). The HPV infection rate increased along with the higher P16 expression intensity. There were statistically significant differences in HPV16, 58, 52, 31, 66, and high-risk hybrid between negative and positive P16 (P<0.05). Conclusion P16 semi-quantitative immunohistochemical score can ob-jectively reflect the degree of CIN lesions. The determination of P16 shows certain significance in the prognosis and outcome of cervical CIN lesions and HPV infection.