Schiffman Mark, Castle Philip E, Jeronimo Jose, Rodriguez Ana C, Wacholder Sholom
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
Lancet. 2007 Sep 8;370(9590):890-907. doi: 10.1016/S0140-6736(07)61416-0.
Cervical cancer is the second most common cancer in women worldwide, and knowledge regarding its cause and pathogenesis is expanding rapidly. Persistent infection with one of about 15 genotypes of carcinogenic human papillomavirus (HPV) causes almost all cases. There are four major steps in cervical cancer development: infection of metaplastic epithelium at the cervical transformation zone, viral persistence, progression of persistently infected epithelium to cervical precancer, and invasion through the basement membrane of the epithelium. Infection is extremely common in young women in their first decade of sexual activity. Persistent infections and precancer are established, typically within 5-10 years, from less than 10% of new infections. Invasive cancer arises over many years, even decades, in a minority of women with precancer, with a peak or plateau in risk at about 35-55 years of age. Each genotype of HPV acts as an independent infection, with differing carcinogenic risks linked to evolutionary species. Our understanding has led to improved prevention and clinical management strategies, including improved screening tests and vaccines. The new HPV-oriented model of cervical carcinogenesis should gradually replace older morphological models based only on cytology and histology. If applied wisely, HPV-related technology can minimise the incidence of cervical cancer, and the morbidity and mortality it causes, even in low-resource settings.
宫颈癌是全球女性中第二常见的癌症，关于其病因和发病机制的知识正在迅速扩展。几乎所有病例都是由大约15种致癌性人乳头瘤病毒（HPV）基因型之一的持续感染引起的。宫颈癌发展有四个主要阶段：宫颈转化区化生上皮的感染、病毒持续存在、持续感染的上皮发展为宫颈癌前病变以及穿过上皮基底膜的侵袭。感染在首次有性行为的年轻女性中极为常见。持续感染和癌前病变通常在5至10年内由不到10%的新感染病例发展而来。浸润性癌在少数癌前病变女性中经过多年甚至数十年才会出现，风险在35至55岁左右达到峰值或平台期。每种HPV基因型都作为一种独立的感染存在，与进化物种相关的致癌风险各不相同。我们的认识带来了改进的预防和临床管理策略，包括改进的筛查测试和疫苗。新的以HPV为导向的宫颈癌发生模型应逐渐取代仅基于细胞学和组织学的旧形态学模型。如果明智地应用，HPV相关技术可以将宫颈癌的发病率及其导致的发病率和死亡率降至最低，即使在资源匮乏的环境中也是如此。
