HPV感染的形态特征及HPV型别与宫颈癌的临床病理联系

Morphological features of HPV infection and the relationship between HPV subtypes and clinicalpathological characteristic of cervical cancer

目的观察人乳头瘤病毒(HPV)感染的形态学改变,分析挖空细胞形态、HPV型别与宫颈鳞状细胞癌临床病理参数间的联系。方法对594例宫颈鳞状细胞癌进行了形态学观察,按照WHO标准进行组织学分型及分级。运用SPF10-PCR技术进行HPV DNA扩增,并采用DEIA(DNA enzyme immunoassay)及LiPA(line probe assay)方法进行DNA检测及分型。结果经检测HPVDNA阳性者581例,其中394例具有HPV感染的组织学特点,即出现典型(104例)或不典型(290例)的挖空细胞,检出率为67.8%。36.2%的角化型及72.2%的高分化宫颈鳞状细胞癌中可见典型挖空细胞,而34.0%的非角化型及50.7%的低分化者中无挖空细胞。在HPV型别检测中,以HPV16阳性最多见为453例,其中高、中、低分化者分别为16例、389例及48例;其次为HPV18共43例,其中中分化者32例,低分化者11例;其他高危型HPV按照阳性数多少依次为HPV31、52、59、58、39、45、33、56、66、68、73,分别为17例、12例、12例、11例、6例、5例、5例、3例、2例、1例、1例;低危型HPV包括6及53各1例,且均同时伴有高危型HPV感染。结果显示,HPV16、HPV18阳性者较其他高危型HPV阳性者发病年龄轻;HPV18阳性者较HPV16阳性者分化程度低;HPV18阳性者较HPV16阳性者无挖空细胞病例所占比例较高(分别为48.8%及31.8%);患者年龄越大FIGO分期越晚。结论挖空细胞形态与宫颈鳞状细胞癌的分化程度密切相关,典型挖空细胞多出现在分化较成熟的癌组织中,而分化较差者常无挖空细胞。HPV16、18是宫颈鳞状细胞癌最重要且最危险的HPV型别。HPV18阳性可能提示宫颈鳞状细胞癌恶性程度高。

Objective To observe the morphological features of cervical squamous cell carcinomas with HPV infection, and to explore the relationship between morphology of HPV subtypes and clinicopathological characteristics of cervical. Methods A total of 594 cases of cervical squamous cell carcinoma were observed. HPV was detected by SPF-10 PCR, subsequently followed by DNA enzyme immunoassay （DEIA） and genotyping by line probe assay （LiPA）. Resuits Out of 581 HPV DNA positive cases, 394 were found to be with typical koilocytes （n = 104） or atypical koilocytes （n = 290）, which was the morphological hallmark of HPV infection. The detection rate was 67. 8%. Typical koilocytes were found in 36. 2% keratinizing and 72.2% of well differentiated cervical squmaous cell carcinoma, but was not found in 34.0% of non-keratinizing and 50. 7% of poorly differentiated ones. The most common HPV type was HPV16 （453 cases）, followed by HPV 18 （43 cases）. The other high-risk HPV subtype were HPV 31, 52, 59, 58, 39, 45, 33, 56, 66, 68 and 73, and each subtype had 17, 12, 12, 11, 6, 5, 5, 3, 2, 1 and 1 cases, respectively. Low-risk HPV included HPV 6 （ n = 1 ） and HPV 53 （ n = 1 ）. Another 8 cases were HPV DNA positive, but their subtypes cannot be identified. Patients infected with HPV 16 or HPV 18 were younger than those infected with other high-risk HPV. The percentage of cases without koilocytes was higher for HPV 18 （48. 8% ） than for HPV 16 （31.8%） positive ones. Conclusion The morphology of koilocytes is closely related to the differentiaon of cervical squmaous cell carcinomas. Typical koilocytes are always found in well differentiated cervical squmaous cell carcinomas, and is absent in poorly differentiated ones. HPV 16 and HPV 18 are the most important but also the most dangerous HPV subtypes. Tumor may have higher malignancy when HPV 18 is positive.