Schiffman Mark, Solomon Diane
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Md 20852, USA.
Arch Pathol Lab Med. 2003 Aug;127(8):946-9. doi: 10.5858/2003-127-946-FTDFTA.
Controversy exists in the United States regarding the proper evaluation and management of low-grade squamous intraepithelial lesion (LSIL) and equivocal (atypical squamous cells of undetermined significance [ASCUS, now ASC-US]) cervical cytologic interpretations. To address this issue, the National Cancer Institute initiated the ASCUS-LSIL Triage Study (ALTS). ALTS is a multicenter, randomized clinical trial designed to evaluate 3 alternative methods of management, namely, immediate colposcopy, cytologic follow-up, and triage by human papillomavirus (HPV) DNA testing. This article summarizes the major findings of ALTS that have been published to date. Patients with ASCUS (n = 3488) or LSIL (n = 1572) were randomly assigned to research arms between November 1996 and December 1998, and were monitored for 2 years. The disease outcome was histologic cervical intraepithelial neoplasia (CIN) 3/cancer. The prevalence of oncogenic HPV was too high to permit effective triage of LSIL using HPV DNA testing by Hybrid Capture 2. However, for the women referred with a cytologic interpretation of ASCUS, HPV triage proved useful, with sensitivity equivalent to immediate colposcopy and a halving of colposcopic referrals. Among older women with ASCUS, HPV testing remained sensitive for detecting CIN 3 and cancer, but the referral percentage was dramatically lower compared to younger women. ALTS yielded insight into the performance of cytology and histopathology; experienced pathologists differed significantly in their interpretations of cervical abnormalities, especially histologic CIN 1 and cytologic ASCUS. Nonetheless, it was possible to distinguish a relatively uncommon type of ASCUS, equivocal for high-grade squamous intraepithelial lesion, that has a high positive predictive value for identifying women with underlying high-grade CIN. Many additional analyses are underway.
在美国，对于低度鳞状上皮内病变（LSIL）以及意义不明确（意义不明确的非典型鳞状细胞[ASCUS，现称为ASC-US]）的宫颈细胞学诊断结果的正确评估和处理存在争议。为解决这一问题，美国国立癌症研究所启动了ASCUS-LSIL分流研究（ALTS）。ALTS是一项多中心随机临床试验，旨在评估三种可供选择的处理方法，即立即进行阴道镜检查、细胞学随访以及通过人乳头瘤病毒（HPV）DNA检测进行分流。本文总结了截至目前已发表的ALTS的主要研究结果。1996年11月至1998年12月期间，将患有ASCUS（n = 3488）或LSIL（n = 1572）的患者随机分配至各研究组，并进行了2年的监测。疾病转归为组织学诊断的宫颈上皮内瘤变（CIN）3/癌。致癌性HPV的患病率过高，以至于无法通过第二代杂交捕获法利用HPV DNA检测对LSIL进行有效的分流。然而，对于细胞学诊断为ASCUS的女性患者，HPV分流被证明是有用的，其敏感性等同于立即进行阴道镜检查，且阴道镜检查转诊率减半。在年龄较大的ASCUS女性患者中，HPV检测对于检测CIN 3和癌仍具有敏感性，但与年轻女性相比，转诊率显著降低。ALTS使人们深入了解了细胞学和组织病理学的表现；经验丰富的病理学家对宫颈异常的解读，尤其是对组织学CIN 1和细胞学ASCUS的解读存在显著差异。尽管如此，还是有可能区分出一种相对不常见的ASCUS类型，即对于高级别鳞状上皮内病变意义不明确，其对于识别患有潜在高级别CIN的女性具有较高的阳性预测价值。许多其他分析正在进行中。
