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人乳头瘤病毒分型与疾病(1)            【字体:
人乳头瘤病毒分型与疾病(1)

       迄今,由于HPV不能在组织细胞中培养,以及其在体外增殖的困难,因此,不能通过分离病毒来确定HPV的型别。HPV分型主要是依靠克隆基因的DNA杂交试验即核酸杂交及酶谱分析等方法来确定。一些分子量相似的HPV通过凝胶电泳均可进行辨认。当HPV DNA被一组特定的限制性内切酶消化时,能建立特征性的酶切图谱。若将凝胶上的DNA酶切片段转移到硝酸纤维素膜上,并与已知的同源性标记探针杂交,根据其DNA的同源性,能将HPV分为不同的型别或不同的亚型。通常在严格的杂交条件下,大约只有13HPV DNA不能相互杂交,其余的HPV DNA均有一定的同源性。当某一未知基因组与任何已知型别HPV进行杂交,其同源性小于50%时,被称为是一个独立的新型;而杂交的同源性大于50%,则称为一个亚型;如果仅出现限制性内切酶的酶切位点的数目不同,则被认为是一个突变株。据此标准,到目前为止,从不同人病灶组织中,已鉴定出HPV70多个亚型,有资料报道为100种以上HPV型,即HPVl100型等。利用DNA同源分析技术等发现某些HPV亚型具同源性,如HPV6型和HPVll型,其核酸同源性达25%,能引起几乎相同的临床损害,在临床上可归于同一亚型。据此,有人认为将来有必要以其临床特征及血清学试验对HPV进行新的分型。

 

       大量研究发现HPV是人类许多疾病的病因,可引起皮肤粘膜、呼吸道等部位一些良性和恶性病变,见表22  

 

 

2-2  HPV引起的疾病

                                                                                                                                                                                                 

                                                                                      

                                                                                                                                                                                                 

皮肤                                                                            疣状表皮发育不良

皮赘

黑素瘤

跖部表皮样囊肿

化脓性肉芽肿

扁平苔藓

银屑病

皮肤疣状癌

皮肤鳞状细胞癌

肛门及生殖器                                                            尖锐湿疣

鲍温样丘疹病

BuschkeLOwenstein肿瘤

女阴假性湿疣 

儿童阴茎硬化性苔藓

宫颈息肉

慢性宫颈炎

生殖器鲍温病

宫颈上皮内瘤

外阴上皮内瘤

阴茎上皮内瘤

肛周上皮内瘤

女阴癌

  呼吸道                                                                        宫颈癌

肛门癌

阴茎癌

睾丸癌

青少年喉头乳头瘤病

喉鳞状细胞癌

鼻窦鳞状细胞癌

扁桃体鳞状细胞癌

肺鳞状细胞癌

  眼部                                                                            眼角结膜癌

眼角结膜乳头瘤病

  口腔及消化道                                                            口腔尖锐湿疣

口腔寻常疣

口腔鳞状细胞乳头瘤

口腔鳞状细胞癌

口腔粘;膜病灶性上皮细胞增生

口腔乳头瘤

食道鳞状细胞癌

  其他                                                                            膀胱癌

前列腺癌

直肠癌

新生儿巨细胞肝炎

新生儿胆管闭锁

甲周部癌

伴有细胞介导免疫缺陷

医源性和HⅣ有关的癌

遗传性

                                                                                                                                                                                                 

 

       随着HPV亚型的不断被发现,人们也逐渐认识到某些特定的HPV亚型与某种疾病或人体某个特定部位的病变以及病变的性质有关。而且不同的疾病可以由某一种HPV亚型或多种HPV亚型引起,而某一种HPV亚型也可引起不同的疾病,见表23、表24

 

但在HPV导致的这些良性或恶性病变中,最常见的是HPV引起的皮肤和肛门生殖器部位的病变,如尖锐湿疣等。

 

 

    2-3  常见皮肤及肛门生殖器部位病变与主要HPV亚型

                                                                                                                                                                                                

                                                                       HPV亚型

                                                                                                                                                                                                

扁平疣                                                         HPV310272841

寻常疣                                                         HPVl24727294054

跖疣                                                             HPVl4

    疣状表皮发育不良                                     HPV581214151719253846

                                                                                      474950

    尖锐湿疣                                                     HPV6111618313334353945

                                                                                                5164~687073

    宫颈上皮内瘤                                             HPV61116183133、·35434451

                                                                                            56  58  61

    鲍温样丘疹病                                             HPVl6183942

        Buschke-lowenstein肿瘤                             HPV6111618

    浸袭性宫颈癌                                             HPVl6183335394244455658

                                                                                             65  66

    阴茎癌                                                         HPVl618

    女阴癌                                                         HPV6.11.16.18

 

 

 

2-4  由不同HPV亚型引起的主要临床病变

                                                                                                                                                                                                

HPV亚型                                             临床病变

                                                                                                                                                                                                

  1                                        掌跖疣

  2                                        寻常疣、丝状疣、跖疣

  3                                        扁平疣

  4                                        寻常疣、跖疣

  5                                        EVEV中的SCC

  6                                        肛门生殖器疣、喉乳头瘤

  7                                        屠夫疣

  g                                        EVEV中的SCC

  9                                        EV

  10                                      扁平疣

  11                                      肛门生殖器疣、喉乳头瘤

  12                                      EV

  13                                      灶状上皮增生

  14                                      EVEV qa~5Ct5

  15                                      EV

  16                                      肛门生殖器疣、CINVINPIN、宫颈癌、BP

  17                                      EV

  18                                      生殖器疣、CIN、宫颈癌

  19                                      EV

  20                                      EVEV中的SCC

  21-25                                 EV   

  26                                      免疫抑制皮肤损害、罕见生殖器损害

  27                                      寻常疣(罕见)

  28                                      扁平疣

  29                                      皮肤疣(罕见)

  30                                      肛门生殖器损害、喉癌

  31                                      肛门生殖器疣、CIN、宫颈癌

  32                                      灶状上皮增生、口腔乳头瘤

  33                                      GINVIN、宫颈癌

  34                                      U腔生殖器疣

  35                                      肛门生殖器疣、CIN、宫颈癌

  36-38                                 EV

  39                                      肛门生殖器疣、CIN、宫颈癌、BP

  40                                      肛门生殖器疣、CINVINPIN

  41                                      扁平疣、皮肤SCC

  42                                      肛门生殖器疣、BP

  43                                      肛门生殖器疣

  44                                      13腔生殖器疣

  45                                      肛门生殖器疣、CIN、宫颈癌

  46                                      归类于HPV20b

  47                                       EVEV中的SCC

  48                                       皮肤疣(罕见)

  49                                       EV

  50                                       EV

  51                                       肛门生殖器疣

  5253                               肛门生殖器疣、CIN、宫颈癌

  54                                       肛门生殖器疣,Buschke-L0wenstein肿瘤(罕见)

  55                                       口腔生殖器疣

  56                                       肛门生殖器疣、CIN、宫颈癌

  57                                       口腔生殖器疣、免疫抑制皮肤损害

  58                                       肛门生殖器疣、CIN、宫颈癌

  59                                       肛门生殖器疣

  60                                       跖部表皮样囊肿

  6162                               VIN

  63                                       皮肤疣(罕见)、足点凹状角化病

  64                                       口腔生殖器疣,VII'

  65                                       色素性扁平疣

  66-68                                  门生殖器疣、CIN、宫颈癌

  69                                       CIN

  70                                       肛门生殖器疣

  72                                       宫颈损害

  73                                       肛门生殖器疣

  75-77                                 免疫抑制皮肤损害