How can the incidence of negative specimens resulting from large loop excision of the cervical transformation zone (LLETZ) be reduced? An analysis ofnegative LLETZ specimens and development of a predictive model

Objective To analyse biopsies of large loop excision of the transformation zone of the cervix; to identify factors associated with negative histology; and to develop predictive models in order to reduce the number of negative loop excisions. Design Retrospective analysis of patient notes and audit database. Setting Colposcopy clinic of a large district general hospital in North Sta ffordshire. Population Four hundred and fifty-two women who underwent a lar ge loop excision of the transformation zone (LLETZ) procedure for suspected cervical intraepithelial neoplasia. Methods Women who underwent a LLETZ procedure were placed in two different groups, one positive for cervical intra epithelial neoplasia and the other negative for cervical intra epithelial neoplasia. Information was obtained on a number of clinical and colposcopic variables. Analysis was undertaken to determine if there were any differences between the two groups. These fa ctors were then identified and three predictive models generated. Receiver- operator characteristic curves were used to assess and test these models. Main outcomes measures To identify factors associated with negative histolo gy on a LLETZ specimen. To predict how to reduce the number of negative LLE TZ specimens. Results Four hundred and fifty-two women underwent a LLETZ procedure, 88 we re negative (19%) and 364 were positive (81%). In women who were treated at their first visit, 56/316 (18%) had negative histology. There were signifi cant associations between negative histology in the LLETZ and negative or l ow grade cytological atypia, negative colposcopic findings and years of age > 50 in both bivariate analysis and stepwise logistic regression. In the p redictive models, the sensitivity ranged between 72% and 80%, the specifici ty 59%-72%, and the area under the receiver-operator characteristic was 0.7 5-0.77. If we had used the predictor models and managed women with negative or low grade cervical atypia and negative colposcopy findings conservative ly, we would have reduced the negative biopsy rate from 19% to 14%, but fiv e cases of high grade disease and 25 cases of low grade disease would have been missed. If we had also included women aged > 50 years in this model, t he negative biopsy rate would have dropped from 19% to 15%, with only one c ase of high grade disease and 11 cases of low grade disease missed. All the se women would require continued cytological and colposcopic surveillance. Importantly, no cases of invasion would have been missed. Conclusion Using a predictive model can reduce the number of negative LLETZ specimens, but at the expense of continued cytological and colposcopic sur veillance and cannot be recommended in normal practice. This raises the que stion whether current standards for negative histology in LLETZ specimens a re set unrealistically high.