Laboratory management of CIN 2: the consensus is consensus.

Since the first associations between human papilloma-virus (HPV)-16 and cervical squamous neoplasia 25 years ago, the field of cervical cancer prevention and precursor diagnosis has continued to evolve, culminating recently with the validation of vaccines that promise to significantly reduce the incidence of this disease. The significance of HPV-16 was appreciated early by its strong association with higher grade cervical intraepithelial neoplasia (CIN) and squamous carci-noma, both of which contained this HPV in nearly 60% of cases. 1,2 Subsequent studies, in vitro and in the clinical setting, have validated the carcinogenic properties of HPV-16 and its significance as a risk factor for the development of high-grade squamous intraepithelial lesions (HSILs; CIN grade 2 or 3) detected by follow-up biopsy. 3,4 Although the strong theoretical link between HPV-16 and cervical premalignancies has been validated by the success of the recently developed vaccines, the link has been inconsistently translated from biologic reality to diagnostic standard. The reason for this is rooted in the historic evolution of precursor management and diagnosis. The first has had an important impact on the second. With the adoption of relatively nontraumatic approaches to cervical neoplasia in the late 1970s—cryotherapy and laser ablation—the principal issues that governed management were ensuring that the patient had a CIN and, if so, excluding CIN 3. CIN 1 was managed typically by cryoablation and CIN 3 by cone biopsy. A diagnosis of CIN 2 (or a small CIN 3 lesion) usually resulted in cryotherapy or laser ablation. In retrospect, what was immediately apparent from this philosophy was that the distinction between CIN 1 and CIN 2 was essentially irrelevant in terms of management. Either cryotherapy or laser could be administered in an outpatient setting to both, and the clinical indications did not require separating CIN 1 from CIN 2 when reviewing the biopsy specimen. 5 In the late 1980s, large loop electrical excision (large loop excision of the transformation zone [LLETZ] or loop electrode excision procedure [LEEP]) was introduced and rapidly embraced by the clinical field. 6 This modality brought with it a fundamental change in the management of women with early cervical neoplasia. First, because LEEP was equivalent to conization, it was not appropriate for women with low-grade squamous intraepithelial lesions (LSILs; condyloma/CIN 1), given the low risk of progression to malignancy. Thus, LSIL was relegated to cytologic follow-up, sparing countless young women the discomfort of cryotherapy or laser ablation. However, …