Authors’ Reply


The authors would like to thank Siegler and Mackuli[1] for their comments on our meta-analysis[2] and for the contribution of their data. The data they present reinforces the finding shown in the prospective studies included in the meta-analysis[2] that the colposcopically directed punch biopsy does have a non-ignorable false-negative rate.[3-6] This false-negative rate was underestimated in the majority of retrospective studies because, typically, only women with a punch-biopsy-proven abnormality would go on to have an excisional biopsy. Moreover, Siegler and Mackuli demonstrate the occurrence of undercalling cervical intraepithelial neoplasia (CIN) lesions in punch biopsies that appear to be more severe in subsequent excisions performed because of suggestive symptoms or discordance between cytology and the histological interpretation of the punch biopsy. This observation is in agreement with findings of the meta-analysis showing a lower pooled sensitivity of CIN2+ punch biopsy for an outcome of CIN2+ (80.1%, 95% CI 73.2–85.6%) compared with the sensitivity of CIN1+ punch biopsy for an outcome of CIN2+ (91.3%, 95% CI 85.3–94.9%).[2]

We echo the appeal for the collection of more data on the performance of colposcopy and the colposcopically directed punch biopsy so as to accurately determine the level of missed disease and to investigate whether this has a clinical implication. Coordination and linking between population-based cytology, colposcopy, pathology and cancer registries would be extremely helpful in avoiding certain biases inherent to clinical patient series.[7]

Conflict of interests

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  2. Conflict of interests
  3. References

MA received funding from the European Commission (FP7, PREHDICT project), IARC, Lyon, France and the Belgian Foundation Against Cancer (Brussels).


  1. Top of page
  2. Conflict of interests
  3. References
  • 1
    Siegler E, Mackuli L. Accuracy of colposcopy-directed punch biopsies. BJOG 2013;120:9023.
  • 2
    Underwood M, Arbyn M, Parry-Smith W, De Bellis-Ayres S, Todd R, Redman CW, et al. Accuracy of colposcopy-directed punch biopsies: a systematic review and meta-analysis. BJOG 2012;119:1293301.
  • 3
    Byrom J, Douce G, Jones PW, Tucker H, Millinship J, Dhar K, et al. Should punch biopsies be used when high-grade disease is suspected at initial colposcopic assessment? A prospective study. Int J Gynecol Cancer 2006;16:2536.
  • 4
    Howe DT, Vincenti AC. Is large loop excision of the transformation zone (LLETZ) more accurate than colposcopically directed punch biopsy in the diagnosis of cervical intraepithelial neoplasia? Br J Obstet Gynaecol 1991;98:58891.
  • 5
    Moss EL, Hadden P, Douce G, Jones PW, Arbyn M, Redman CW. Is the colposcopically directed punch biopsy a reliable diagnostic test in women with minor cytological lesions? J Low Genit Tract Dis 2012;16:4216.
  • 6
    Zuchna C, Hager M, Tringler B, Georgoulopoulos A, Ciresa-Koenig A, Volgger B, et al. Diagnostic accuracy of guided cervical biopsies: a prospective multicenter study comparing the histopathology of simultaneous biopsy and cone specimen. Am J Obstet Gynecol 2010;203:321 e16.
  • 7
    Arbyn M, Anttila A, Jordan J, Ronco G, Schenck U, Segnan N, et al. European guidelines for quality assurance in cervical cancer screening. Second edition – summary document. Ann Oncol 2010;21:44858.