Gervaz P, Hirschel B, Morel P
Department of Surgery, University Hospital Geneva, Geneva, Switzerland.
Br J Surg. 2006 May;93(5):531-8. doi: 10.1002/bjs.5376.
Squamous cell carcinoma of the anal canal provides a model for studying the contribution of human papillomavirus (HPV) and human immunodeficiency virus (HIV) infection to the development of neoplasia. This paper reviews the existing literature relating to the molecular biology of anal squamous cell carcinoma and proposes a theory of pathogenesis.
A Medline literature search was performed to identify English articles on the pathogenesis of squamous cell carcinoma of the anus; further articles were obtained from the references quoted in the literature initially reviewed.
HPV infection and subsequent HPV DNA integration are necessary, but not sufficient, to cause cancer progression. Loss of heterozygosity at 11q23 is the most consistent genomic change observed. Loss of heterozygosity at 17p, 18q and 5q is frequently observed in tumours of HIV-negative patients, but not in those of HIV-positive patients. Current data suggest that mutations in p53, DCC and APC tumour suppressor genes contribute to the stepwise progression of anal squamous cell carcinoma in immunocompetent individuals.
In comparison with immunocompetent individuals, HIV-positive patients have persistent HPV infection in the anal canal. In this population, microsatellite instability, rather than chromosomal instability, appears to be a preferred pathway for rapid progression towards invasive carcinoma.
肛管鳞状细胞癌为研究人乳头瘤病毒（HPV）和人类免疫缺陷病毒（HIV）感染对肿瘤形成的作用提供了一个模型。本文综述了有关肛管鳞状细胞癌分子生物学的现有文献，并提出了一种发病机制理论。
进行了一项医学文献检索，以确定关于肛门鳞状细胞癌发病机制的英文文章；通过最初查阅文献中引用的参考文献获得了更多文章。
HPV感染及随后的HPV DNA整合是癌症进展的必要条件，但并非充分条件。观察到的最一致的基因组变化是11q23杂合性缺失。17p、18q和5q杂合性缺失在HIV阴性患者的肿瘤中经常观察到，但在HIV阳性患者中未观察到。目前的数据表明，p53、DCC和APC肿瘤抑制基因的突变有助于免疫功能正常个体中肛管鳞状细胞癌的逐步进展。
与免疫功能正常的个体相比，HIV阳性患者肛管中存在持续性HPV感染。在这一人群中，微卫星不稳定性而非染色体不稳定性似乎是向浸润性癌快速进展的首选途径。
