Risk of preterm birth following surgical treatment for cervical disease: executive summary of a recent symposium

Abstract

We report on a symposium held in London, UK, on 16 February 2015 to discuss the association between surgical treatment of cervical intraepithelial neoplasia (CIN) and subsequent preterm birth, and to consider appropriate recommendations for the treatment of CIN and management of treated women during pregnancy. The meeting focused on CIN grades 2 and 3 that have been managed surgically. Clinical practice varies internationally: in some countries knife excision is common; in others, laser ablation is the treatment of choice; and in others, treatment predominantly involves outpatient large loop excision of the transformation zone (LLETZ), also called loop electrosurgical excision procedure (LEEP). The meeting was part of the dissemination strategy of the National Institute for Health Research (NIHR)-funded PaCT study (preterm delivery after treatment of the cervical transformation zone). Around 50 people attended, including gynaecologic oncologists, (nurse and medical) colposcopists, obstetricians, and epidemiologists. The authors of this executive summary include the speakers at the symposium, who are also authors of important papers in the subject area, and the symposium chairs, to provide an independent opinion on the views expressed by the audience. Further details on the expertise of the authors can be found in the contribution to authorship. Meta-analysis suggested that pregnant women previously treated by LLETZ are at approximately twice the risk of a preterm birth than pregnant women in general.1-3 A study from England,4 and a recent meta-analysis,3 found a much lower relative risk and no association after adjusting for confounding factors. More recent research suggests that the increased risk may be associated with large excisions alone (10–14 mm, and particularly >15 mm), and that the reason for the lack of association in some studies was that the majority of women treated had small excisions.5 Assuming the observed associations are causal, how should guidelines be modified to minimise the risk of causing preterm deliveries whilst still effectively preventing progression from CIN to invasive cervical cancer? In thinking about the balance between the harms and benefits of treatment it is important to know about the long-term consequences of late preterm deliveries (34–36 weeks of gestation). Even if the association between LLETZ and preterm birth is not causal, having identified a high-risk group there is a question as to how they should be managed obstetrically. The first part of the meeting focused on the results of international studies on the association between the treatment of CIN and subsequent risk of preterm delivery. The second part of the meeting aimed to put the evidence regarding the risk of preterm birth in the context of the wider aims of cervical screening (to prevent cervical cancer by appropriate treatment of precancerous lesions). The speakers explored the use of ablative treatment in colposcopy and the need for quality assurance of the programme. There was consensus (level 5) among the audience on the following points. There was a lack of consensus regarding ablative treatment. The majority view was that ablative treatment is not, at this time, an appropriate alternative to LLETZ in established cervical screening programmes in high-income countries. Concern was raised regarding the risk of invasive cancer after destructive treatments.17, 18 Others felt that ablative treatment is safe for CIN2 and for type–I transformation zone (defined as completely ectocervical and fully visible),19 and was less likely to result in over treatment (and increased risk of preterm birth) when carried out by a less experienced colposcopist. The counter argument was that without measurements of the volume of tissue destroyed, and without evidence of whether there were clear margins or occult invasive cancer, it was impossible to quality assure ablative treatment. The majority view was that ablative treatments are acceptable for CIN2, provided the whole lesion is visualised. Although a randomised controlled trial of ablative treatment versus excision for type–I lesions was proposed, it was agreed that any such trial would need to be extremely large and to have long-term follow-up. The majority view was that such a trial was not justified, taking into account that small excision appears to be safe and that the future demand for treatment of CIN3 will be dramatically reduced by human papilloma virus (HPV) vaccination. Finally, the meeting focused on the long-term impact of preterm birth and the obstetric management of high-risk pregnancies. There is growing evidence of small effects on health and behaviour in children born late preterm compared with those born at 40 weeks of gestation (level 2b). For instance, 16.6% of infants born at 33–34 weeks of gestation and 13.5% of infants born at 35–36 weeks of gestation had an emergency hospital admission for respiratory disease by the age of 1 year, compared with