P16和Ki-67与宫颈癌患者HPV持续性感染的相关性研究

Relationship between Expression of P16 and Ki-67 and Persistent Infection of HPV in Cervical Carcinoma Patients

摘要: 目的：探讨P16和Ki-67表达与宫颈病变之间的关系，评估P16和Ki-67作为高危型人乳头瘤病毒(hr-HPV)持续感染预后标记物的意义。方法：纳入宫颈活检标本1369例，无癌前病变(NEG) 392例，宫颈上皮内瘤变I (CIN I) 519例，CIN II 257例，CIN III 154例，鳞状细胞癌(SCC) 47例。此外，306名CIN I患者被纳入为期12个月的随访中，使用HPV特异性引物通过聚合酶链反应方法检测宫颈分泌物中hr-HPV，随访期内每6个月检测一次。133名患者持续感染hr-HPV，94名一过性感染，79名未感染hr-HPV。免疫组织化学法检测P16和Ki-67的表达。P16和Ki-67的染色结果分为四类：阴性，1+，2+和3+。结果：与NEG相比CINs和SCC中P16和Ki-67的表达均显著增加(P < 0.01)。CIN III中P16和Ki-67的表达与CIN II相比均无显著性差异(P > 0.05)。P16阳性率与hr-HPV持续感染正相关(P < 0.05)。hr-HPV感染患者中P16以及Ki-67阳性率显著高于未感染hr-HPV的患者(P < 0.05)。结论：P16和Ki-67可提高宫颈病变的诊断准确性，P16表达与CIN I期患者hr-HPV持续感染存在相关性。

Abstract: Objective: To determine the association between the expression of P16 and Ki-67 and cervical le-sions, and to evaluate the role of P16 and Ki-67 as prognostic markers for persistent high risk human papillomavirus (hr-HPV) infection. Methods: Totally 1369 cases of cervical biopsies were enrolled, 392 cases with negative for dysplasia (NEG), 519 with cervical intraepithelial neoplasia I (CIN I), 257 with CIN II, 154 with CIN III and 47 with cervical squamous cell carcinoma (SCC). Fur-thermore, 306 women with CIN I were recruited into 12-month follow-up, and HPV specific gene detection by polymerase chain reaction was used to detect hr-HPV of cervical secretions at 6-month-interval for 12-month follow-up period. 133 women were infected with persistent hr-HPV, 94 with transient infection and 79 not infected with hr-HPV. The expression of P16 and Ki-67 was evaluated by immunohistochemical method. The immunostaining results of P16 and Ki-67 were classified into four categories: negative, 1+, 2+ and 3+. Results: There was significant increase in the expression of P16 and Ki-67 (P < 0.01) from NEG to SCC. There was no significant difference in the expression of P16 and Ki-67 between CIN II and CIN III (P > 0.05). Ratio of P16 positivity was positive correlated with persistent hr-HPV infection (P < 0.05). Ratios of P16 and Ki-67 in hr-HPV infection group were significantly higher than that of non-infection group (P < 0.05). Conclusion: P16 and Ki-67 can improve the diagnostic accuracy of cervical lesions. P16 expression is correlated with persistent hr-HPV infection in CIN I patients.