Cotton Seonaidh C, Sharp Linda, Little Julian, Duncan Ian, Alexander Lindyanne, Cruickshank Margaret E, Gray Nicola M, Jenkins David, Philips Zoë, Robertson Alistair, Seth Rashmi
Department of Public Health, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen, AB25 2ZD, UK.
Contemp Clin Trials. 2006 Oct;27(5):449-71. doi: 10.1016/j.cct.2006.04.001. Epub 2006 Apr 28.
Cervical screening reduces the risk of cervical cancer by detecting and treating cervical intraepithelial neoplasia (CIN). The management of women with low-grade cervical abnormalities is controversial. Two management policies exist: repeat smears in primary care and colposcopy examination. It is not clear which of these is the more effective and efficient. There is also uncertainty as to the most effective and efficient management of women at colposcopy when an area of abnormality is seen on the cervix - immediate treatment or biopsy and selective recall for treatment if the biopsy result suggests this is necessary. The result of a human papillomavirus (HPV) test might assist in deciding the appropriate management of women with low-grade abnormalities. TOMBOLA, a pragmatic randomised-controlled trial set within the cervical screening programmes in Scotland and England, addresses these three areas of uncertainty. Almost four and a half thousand women aged 20-59 with a low-grade cervical abnormality have been recruited and randomised to either repeat smears or colposcopy examination. Women in the colposcopy arm of the trial are further randomised to a policy of either immediate treatment or biopsy and selective recall for treatment if they have an abnormal transformation zone. Women are followed up to an exit examination at 3 years. HPV testing is undertaken at recruitment and at the exit examination. The primary endpoint is cumulative incidence of CIN2/3. A range of other clinical, psychosocial and economic outcomes is being considered. This paper describes the design of the trial, and discusses the rationale underlying aspects of the design and the challenges faced in designing and implementing the trial.
宫颈筛查通过检测和治疗宫颈上皮内瘤变（CIN）降低宫颈癌风险。对低度宫颈异常女性的管理存在争议。现有两种管理策略：基层医疗中重复涂片检查和阴道镜检查。尚不清楚哪种策略更有效且高效。对于在阴道镜检查中发现宫颈存在异常区域的女性，最有效且高效的管理方式是立即治疗还是活检，若活检结果表明有必要则选择性召回治疗，这也存在不确定性。人乳头瘤病毒（HPV）检测结果可能有助于决定对低度异常女性的恰当管理。TOMBOLA是一项在苏格兰和英格兰的宫颈筛查项目中开展的实用随机对照试验，解决了这三个不确定领域的问题。近4500名年龄在20至59岁、有低度宫颈异常的女性被招募并随机分为重复涂片检查组或阴道镜检查组。试验中接受阴道镜检查的女性进一步随机分为立即治疗策略组，或若转化区异常则进行活检并选择性召回治疗组。对女性进行随访直至3年后的退出检查。在招募时和退出检查时进行HPV检测。主要终点是CIN2/3的累积发病率。还在考虑一系列其他临床、社会心理和经济结局。本文描述了该试验的设计，并讨论了设计背后的原理以及设计和实施该试验所面临的挑战。
