Reliability of negative cone specimens of the cervix: A review

Cervical conization specimens with a negative result for high-grade lesion are not infrequent in clinical practice and there are no protocols to address this issue. The purpose of this manuscript is to analyze factors that affect the reliability on these situations and provide recommendations to guide the gynecologists on their practice.

We searched original articles on Pubmed/Medline database that analyzed negative cones using different combinations of descriptors. There were no restrictions regarding the language or the year of publication.

Nineteen articles were selected and a total of 7310 cones analyzed. The negative excision rate ranged from 10 to 35%. Among the reasons to explain absence of lesion, the most frequent were errors in colposcopy, spontaneous lesion regression, complete removal of small lesions during biopsy, errors in the pre-conization material, false-negative results, and excisional error. Pathological specimen review and application of immunohistochemical biomarkers p16 and Ki-67 seemed to improve accuracy and help in challenging differential diagnosis. Recurrence was detected in up to 30%, as seen in positive cones with compromised margins. Importantly, testing for HPV demonstrated benefits in reducing the number of negative cones.

Several factors could contribute to a negative result in a conization. Our main recommendations include: interval of 4-6 weeks between biopsy and conization, repeat the colposcopy during the excision, consider short-term reevaluation for small colposcopy lesions, perform deep sectioning levels in the paraffin block, use of immunohistochemical markers, HPV testing, and strict surveillance during follow-up as performed for positive cases with compromised margins.