Brenna Sylvia Michelina Fernandes, Syrjänen Kari Juhani
State Health Department, Maternity Hospital Leonor Mendes de Barros, São Paulo, Brazil.
Sao Paulo Med J. 2003 May 5;121(3):128-32. doi: 10.1590/s1516-31802003000300009. Epub 2003 Aug 8.
The rapid progress in molecular biology has allowed the identification of the genes involved in different functions of normal cells and has also improved our understanding of the mechanisms of human carcinogenesis. The human papillomavirus (HPV) is a small double-stranded DNA tumor virus and its genes can manipulate cell cycle control to promote viral persistence and replication. The E6 and E7 proteins of high-risk HPV bind to cell cycle regulatory proteins and interfere with both G1/S and G2/M cell cycle checkpoints much more effectively than the low-risk HPV. The difference between the ability of low and high-risk HPV types to induce immortalization and transformation may well lie in their abilities to interact with the various cell cycle components, resulting in the loss of multiple cell cycle checkpoints, which are important in host genome fidelity, thus potentially resulting in accumulation of genetic abnormalities. Cervical cancer is one of the leading malignancies in women worldwide, with substantial morbidity and mortality. According to current concepts, HPV is recognized as the single most important causal agent in the pathogenesis of this cancer. HPV infection clearly precedes the development of malignancy, while being regularly associated with cervical cancer precursor lesions (all grades of squamous intraepithelial lesions). HPV-infected low-grade squamous intraepithelial lesion (SIL) has three possible outcomes: a) it may regress; b) it can persist; or c) it can make a clinical progression to in situ or invasive carcinoma. It has been well established by prospective cohort studies that the spontaneous regression rate increases in parallel with follow-up duration. In contrast, the clinical progression of lesions usually takes place quite rapidly, i.e. during the first two years from diagnosis. The mechanisms responsible for this divergent clinical behavior of HPV-associated squamous intraepithelial lesions are largely unknown, but currently under intense study in different laboratories worldwide.
分子生物学的迅速发展使得人们能够鉴定出参与正常细胞不同功能的基因，也增进了我们对人类致癌机制的理解。人乳头瘤病毒（HPV）是一种小型双链DNA肿瘤病毒，其基因可操纵细胞周期调控以促进病毒的持续存在和复制。高危型HPV的E6和E7蛋白与细胞周期调节蛋白结合，比低危型HPV更有效地干扰G1/S和G2/M细胞周期检查点。低危型和高危型HPV诱导永生化和转化能力的差异很可能在于它们与各种细胞周期成分相互作用的能力，导致多个细胞周期检查点丧失，而这些检查点对宿主基因组保真度很重要，从而可能导致遗传异常的积累。宫颈癌是全球女性主要的恶性肿瘤之一，发病率和死亡率都很高。根据目前的概念，HPV被认为是这种癌症发病机制中唯一最重要的致病因素。HPV感染显然先于恶性肿瘤的发生，且经常与宫颈癌前病变（所有级别的鳞状上皮内病变）相关。HPV感染的低级别鳞状上皮内病变（SIL）有三种可能的结果：a）它可能消退；b）它可能持续存在；或c）它可能临床进展为原位癌或浸润癌。前瞻性队列研究已经明确证实，自发消退率随随访时间的延长而增加。相比之下，病变的临床进展通常相当迅速，即在诊断后的头两年内。HPV相关鳞状上皮内病变这种不同临床行为的机制在很大程度上尚不清楚，但目前全球不同实验室正在对此进行深入研究。
