Stark L A, Arends M J, McLaren K M, Benton E C, Shahidullah H, Hunter J A, Bird C C
Department of Pathology, University of Edinburgh, UK.
Br J Cancer. 1994 Feb;69(2):222-9. doi: 10.1038/bjc.1994.43.
It is well established that renal allograft recipients (RARs) have an increased incidence of viral warts and premalignant and malignant cutaneous lesions, and the risk of their development increases in proportion to duration of graft survival. It has been postulated that, in addition to the effects of prolonged immunosuppression and previous sun exposure, human papillomaviruses (HPV) may also contribute to the carcinogenic process. In this study, the prevalence of HPV DNA was examined in a range of premalignant and malignant cutaneous tumours from 50 immunosuppressed patients (47 renal allograft recipients plus three cardiac allograft recipients) and 56 immunocompetent patients using Southern hybridisation as a low-stringency screening method and type-specific polymerase chain reaction (PCR) assays for eight HPV types. The combined results for renal allograft recipients show that HPV DNA was detectable in 79% of viral warts, 42% of premalignant keratoses, 33% of intraepidermal carcinomas, 43% of invasive squamous cell carcinomas and 16% of uninvolved skin specimens (squamous cell carcinomas/renal allograft recipients significantly different at P < 0.05 from uninvolved skin specimens/renal allograft recipients). In immunocompetent patients the pattern of HPV DNA prevalence was 100% for viral warts; 25% for keratoses, 23% for intraepidermal carcinomas, 22% for squamous cell carcinomas and 8% for uninvolved skin. No single HPV type predominated in tumour specimens from either group. More tumours were found to contain HPV DNA by Southern hybridisation analysis than PCR, indicating the presence of HPV types other than HPV 1, 2, 5, 6, 8, 11, 16 and 18 in some tumours. However, 'low cancer risk' HPV types 1, 2 and 6 as well as 'high cancer risk' HPV types 5 and 16 were specifically detected by PCR in a small number of neoplasms. These data suggest that multiple HPV types may contribute to cutaneous neoplasia in RARs and that they appear to act early in the process of carcinogenesis, perhaps by functioning as tumour promoters via stimulation of cell proliferation.
肾移植受者(RARs)发生病毒疣以及皮肤癌前病变和恶性病变的几率增加,且这些病变发生的风险随着移植肾存活时间的延长而升高,这一点已得到充分证实。据推测,除了长期免疫抑制和既往日晒的影响外,人乳头瘤病毒(HPV)可能也参与了致癌过程。在本研究中,采用Southern杂交作为低严谨度筛查方法,并运用针对8种HPV类型的型特异性聚合酶链反应(PCR)检测,对50例免疫抑制患者(47例肾移植受者加3例心脏移植受者)和56例免疫功能正常患者的一系列皮肤癌前病变和恶性肿瘤中的HPV DNA流行情况进行了检测。肾移植受者的综合检测结果显示,在79%的病毒疣、42%的癌前角化病、33%的表皮内癌、43%的浸润性鳞状细胞癌以及16%的未受累皮肤标本中可检测到HPV DNA(鳞状细胞癌/肾移植受者与未受累皮肤标本/肾移植受者相比,差异有统计学意义,P<0.05)。在免疫功能正常的患者中,HPV DNA流行情况为:病毒疣中为100%;角化病中为25%,表皮内癌中为23%,鳞状细胞癌中为22%,未受累皮肤中为8%。两组患者的肿瘤标本中均没有单一HPV类型占主导。Southern杂交分析比PCR检测发现更多肿瘤含有HPV DNA,这表明在某些肿瘤中存在HPV 1、2、5、6、8、11、16和18以外的HPV类型。然而,通过PCR在少数肿瘤中特异性检测到了“低癌症风险”的HPV 1、2和6型以及“高癌症风险”的HPV 5和16型。这些数据表明,多种HPV类型可能与肾移植受者的皮肤肿瘤形成有关,并且它们似乎在致癌过程的早期就发挥作用,可能是通过刺激细胞增殖作为肿瘤促进剂。