Pitfalls in the Diagnosis of Cervical Intraepithelial Neoplasia 1

OBJECTIVE: This review article outlines the issues involved in (1) the cytologic diagnosis of low-grade squamous intra-epithelial lesion (cervical intraepithelial neoplasia [CIN] 1), (2) histologic diagnosis of CIN 1, (3) the advantages and disadvantages of various management strategies for CIN 1 confirmed by biopsy, and (4) the evolving technology that may be useful for predicting the course of the disease. MATERIALS AND METHODS: A MEDLINE search was conducted using the search terms cervical intraepithelial neoplasia, low-grade dysplasia, mild dysplasia, low-risk squamous intraepithelial lesion, mild dyskaryosis, HPV, colposcopy, histology, and cytology. RESULTS.: Using a loop electrosurgical excision procedure or cone biopsy assessment of the cervix as the gold standard, a cytologic assessment of CIN 1 alone results in a high false-positive rate (51.5%) and a false-negative rate (24%) for CIN 3. The appropriate second test after low-grade squamous intraepithelial lesion (CIN 1) cytologic results includes repeat cervical cytologic analysis. Subsequent human papillomavirus testing provides no advantage and increases the cost of care. Immediate referral to colposcopy is costly but minimizes the percent of women lost to follow-up. Using a loop electrosurgical excision procedure or cone biopsy assessment of the cervix as the gold standard, the colposcopically directed biopsy may give a false-positive result (11.7%) or false-negative result (up to 31%) for CIN 3. One contributing issue is the moderate interobserver reliability of histologic analysis (kappa= 0.46). There are advantages and disadvantages to both the immediate and expectant management strategies. The most crucial concern for immediate treatment is overtreatment, and that for expectant management the high rate of patients lost to follow-up. Novel technologies, including MIB-1, p16(INK)4a, and genetic assessments, may be helpful in predicting those CIN 1 lesions destined to progress or to persist. CONCLUSIONS: The cytologic and histologic diagnosis of CIN 1 is fraught with problems related to the subjectivity of the diagnosis. Both management options are also fraught with concerns. Any technique that can better predict disease course would be an advantage to the care of women with this abnormality.