Bouda M, Gorgoulis V G, Kastrinakis N G, Giannoudis A, Tsoli E, Danassi-Afentaki D, Foukas P, Kyroudi A, Laskaris G, Herrington C S, Kittas C
Department of Histology and Embryology, School of Medicine, University of Athens, Greece.
Mod Pathol. 2000 Jun;13(6):644-53. doi: 10.1038/modpathol.3880113.
Studies on the involvement of the human papillomavirus (HPV) in initiation and progression of oral neoplasia have generated conflicting results. The observed discrepancy is attributable mainly to the varying sensitivity of the applied methodologies and to epidemiologic factors of the examined patient groups. To evaluate the role of HPV in oral carcinogenesis, we analyzed 53 potentially neoplastic and neoplastic oral lesions consisting of 29 cases of hyperplasia, 5 cases of dysplasia, and 19 cases of squamous cell carcinomas, as well as 16 oral specimens derived from healthy individuals. A highly sensitive nested polymerase chain reaction (PCR) assay was used, along with type-specific PCR, restriction fragment length polymorphism analysis, dot blotting, and nonisotopic in situ hybridization. Nested PCR revealed the presence of HPV DNA in 48 of the 53 (91%) pathologic samples analyzed, whereas none (0%) of the normal specimens was found to be infected. Positivity for HPV was independent of histology and the smoking habits of the analyzed group of patients. At least one "high risk" type, such as HPV 16, 18, and 33, was detected by type-specific PCR in 47 (98%) infected specimens, whereas only 1 (2%) squamous cell carcinoma was solely infected by a "low risk" type (HPV 6). HPV 16 was the prevailing viral type, being present in 71% of infected cases. Single HPV 16 and HPV 18 infections were confirmed by restriction fragment length polymorphism. HPV 58 was detected by dot blotting in three hyperplastic lesions. HPV positivity and genotyping were further confirmed, and the physical status of this virus was evaluated by nonisotopic in situ hybridization. Diffuse and punctate signals, indicative of the episomal and integrative pattern of HPV infection, were observed for low- and high-risk types, respectively. Our findings are suggestive of an early involvement of high-risk HPV types in oral carcinogenesis.
关于人乳头瘤病毒（HPV）在口腔肿瘤发生起始和进展过程中的作用研究，结果相互矛盾。观察到的差异主要归因于所应用方法的不同敏感性以及所检查患者群体的流行病学因素。为评估HPV在口腔癌发生中的作用，我们分析了53例潜在的肿瘤性和肿瘤性口腔病变，包括29例增生、5例发育异常和19例鳞状细胞癌，以及16例来自健康个体的口腔标本。使用了一种高度敏感的巢式聚合酶链反应（PCR）检测方法，以及型特异性PCR、限制性片段长度多态性分析、斑点印迹和非同位素原位杂交。巢式PCR显示，在分析的53例病理样本中有48例（91%）存在HPV DNA，而正常标本中无一例（0%）被发现感染。HPV阳性与所分析患者组的组织学和吸烟习惯无关。通过型特异性PCR在47例（98%）感染标本中检测到至少一种“高危”型，如HPV 16、18和33，而仅1例（2%）鳞状细胞癌仅被“低危”型（HPV 6）感染。HPV 16是主要的病毒类型，存在于71%的感染病例中。通过限制性片段长度多态性证实了单一HPV 16和HPV 18感染。通过斑点印迹在3例增生性病变中检测到HPV 58。通过非同位素原位杂交进一步证实了HPV阳性和基因分型，并评估了该病毒的物理状态。分别观察到低危型和高危型的弥漫性和点状信号，分别指示HPV感染的游离型和整合型模式。我们的研究结果提示高危型HPV在口腔癌发生中早期即有参与。
