高危型HPV负荷量与宫颈上皮内瘤样变级别、Ki-67和P16^(ink4a)表达的关系及随访观察

Correlations of High-risk Human Papillomaviral Load to Cervical Intraepithelial Neoplasia Grades, Expression of Ki-67 and P16^(ink4a) and Follow-up

背景与目的:高危型人乳头瘤病毒(human papillomavirus,HPV)感染是宫颈癌的主要致病原因。HPV负荷量与宫颈癌的关系存在争论,其与肿瘤标记物的关系研究很少。本研究旨在初步探讨高危型HPV负荷量与宫颈上皮内瘤样变(cervical intraepithelial neoplasia,CIN)级别、Ki-67和p16ink4a表达及术后再次出现细胞学异常之间的关系。方法:选择61例CIN患者宫颈组织石蜡标本(CINⅠ8例、CINⅡ12例、CINⅢ41例),免疫组化检测Ki-67、p16ink4a表达。所有患者术前均用第二代杂交捕获法(hybridcaptureⅡ,HCⅡ)检测HPV负荷量,术后进行随访。结果:高危型HPV负荷量与CIN等级、Ki-67和p16ink4a表达之间呈等级正相关(r分别为0.288、0.318、0.336,P<0.05)。经过平均18.5个月的随访,发现6例患者再次出现宫颈脱落细胞学异常,其中5例术前HPV负荷量≥100RLU/PC、<1000RLU/PC,1例≥1000RLU/PC,但术前HPV负荷量与术后再次出现细胞学异常无关(P>0.05)。年龄、产次、组织学诊断、Ki-67与p16ink4a表达强度亦与术后细胞学异常无关。结论:HPV负荷量与CIN进展、细胞恶性程度增高呈正相关。尽管HPV负荷量与术后再次出现细胞学异常无关,但对病毒负荷量>100RLU/PC的患者仍应严密随访。

BACKGROUND ＆ OBJECTIVE： It is well known that high-risk human papillomavirus （HPV） infection is the major cause of cervical cancer. However, the relation between cervical cancer and high-risk HPV load is uncertain, and there are only a small number of reports studying the correlation between high-risk HPV load and tumor markers. This study was to investigate the correlations of high-risk HPV load to the grade of cervical intraepithelial neoplasia （CIN）, expression of Ki-67 and P16^ink4a in the cervical lesion, and the abnormal cytology after surgery. METHODS： The expression of Ki-67 and P16^ink4a in 8 specimens of CIN Ⅰ , 12 specimens of CIN Ⅱ , and 41 specimens of CIN Ⅲ were detected by immunohistochemistry. All the patients received high-risk HPV load detection using hybrid capture Ⅱ （HC Ⅱ ） before operation and were followed up afterwards. RESULTS. The highrisk HPV load was positively correlated to the CIN grade and expression of Ki-67 and P16^ink4a with correlation coefficients of 0.288, 0.318, and 0.336, respectively （P〈0.05）. After a mean follow-up of 18.5 months, 6 patients were found abnormal cytological smears again, whose HPV loads were over 100 RLU/PC before operation. Five out of the 6 patients had the HPV loads between 100 to 1000 RLU/ PC before operation and the remaining one had the HPV load of over 1000 RLU/PC. However, no statistical differences were observed among the 3 groups of different viral loads （〈100 RLU/PC, 100 to 〈1 000 RLU/PC, ≥1 000 RLU/PC）. Age, parity, CIN grades, expression of P16^ink4a and Ki-67 had no predictive significance for the abnormal cytology after operation. CONCLUSIONS. The high-risk HPV load has positive correlation to the progression of cervical lesion and increased malignancy of cells. Although the high-risk HPV load have no relation to the abnormal cytology after operation, patients with the viral load of over 100 RLU/PC should be paid more attention.