喉癌和喉乳头状瘤与HPV感染和P16蛋白的关系

Human Papilloma Virus Infection and Expression of P16 Protein in Laryngeal Papilloma and Laryngeal Carcinoma

目的:探讨人类乳头状瘤病毒(Human Papillomavirus,HPV)感染和抑癌基因P16的失活与喉癌(Laryneal carcinoma,LC)和喉乳头状瘤(Laryngeal papilloma,LP)发生的相关性,以进一步阐明LC和LP的病因和发病机理。方法:收集LP 46例[其中成人型喉乳头状瘤(ALP)21例,青少年型喉乳头状瘤(JLP)25例]、LC 26例、癌旁正常组织6例、声带小结15例,用标记的HPV_(1,6,8,11,13,16,18,30,31,32,33,45,51)通用引物直接法原位PCR方法和免疫组化(SP法)方法分别检测HPV-DNA和P16蛋白。结果:1、HPV阳性率JLP组(84%,21/25)显著高于ALP组(38.1%,8/21)、LC组(19.2%,5/26)、声带小结组(0%,0/15)和癌旁组织组(0%,0/6)(卡方检验,P<0.05);而ALP组、LC组、声带小结组和癌旁组织组之间HPV阳性率无显著差别(卡方检验或Fisher’s精确概率法,P>0.05)。2、P16蛋白的阳性率ALP组(57.1%,12/21)和LC组(38.5%,10/26)均显著低于JLP组(88%,22/25)、癌旁组织组(100%,6/6)和声带小结组(93.3%,14/15)(卡方检验,P<0.05);ALP组和LC组之间及JLP组和声带小结组之间P16蛋白阳性率无显著差别(卡方检验,P>0.05)。3、LP中P16蛋白的阳性率在HPV阳性和阴性组中有显著差别(x^2检验,P<0.05);喉癌中P16蛋白的阳性率在HPV阳性组和阴性组中无显著差别(Fisher’s精确概率法,P>0.05)。结论:青少年型喉乳头状瘤的发生与HPV感染密切相关而与抑癌基因P16的失活无明显相关。成人型喉乳头状瘤和喉癌的发和与HPV感染可能无明显关系,而与抑癌基因P16的失活密切相关。HPV感染和P16基因失活在致瘤过程中无明显协同作用。

Object: To evaluate the role of human papilloma virus (HPV) infection end inactivation of P16 gene in laryngeal papilloma (LP) and laryngeal squamous cell carcinoma (LC). Method: HPV consensus primers direct in situ polymerase chain reaction (ISPCR) and immunohistochemical method were applied to detect the presence of HPV genomes(1,6,8,11,13,16.18,30.31,32,33,45,51) and the expression of P16 protein respectively in 93 cases of formalin - fixed, paraffin - imbedded specimens, which contained 46 cases of LPs [adult- onset laryngeal papilloma (ALP) 21, juvenile onset laryngesl papilloma (JLP) 25], 26 ceses of LCs, 6cases of normal tissues adjacent to carcinoma, end 15 cases of vocal noduli, Results: 1、The differences of positive rates of HPVDNA in JLP group (84%, 21/25) end other groups were significant statistically (X^2 test, P<0.05). The differences of positive rates of HPV- DNA in ALPs (38.1%, 8/21), in LCs (19.2%, 5/26), invocal noduli (0%, 0/15), end in normal tissues adjacent to carcinoma (0%, 0/6) were not significant statistically (X^2 test or Fisher's exact probabitity test, P>0.05). 2, The positive rates of expression of P16 protein in ALP group (57.1%, 12/21) and LC group (38.5%, 10/26) were significantly lower than that in vocal noduli group (93.3%, 14/15), in JLP group (88%, 22/25), end in normal tissues adjacent to carcinoma group (100%, 6/6) (X^2 test or Fisher's exact probability test, P>0.05). There were no significant differences of positive rates of expression of P16 protein between in ALP group and in LC grup and between in JLP group and in vocal nodule group (X^2 test, P>0.05) 3, In LPs the difference of positive rates of expression of P16 protein between in HPV positive cases and in HPV negative cases was significant statistically (X^2 test, P<0.05); In LCs, there was no difference in the rate of expression of P16 protein between the two teams (Fisher's exact probability test, P>0.05). Conclusion: The pathogenesis of JLP is closely associated with HPV infection and unassociated with the inactivation of P16 gene. Conversely, the pathogeneses of ALP and LC are associated with the inactivation of P16 gene and unassociated with the HPV infection. The infection of HPV and the inactivation of P16 gene may play a role in pathogenesis of tumor, respectively.