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A 36-year-old woman presented for follow-up of a persistently abnormal Papanicolaou (Pap) test. She is a smoker and has had multiple new sexual partners in the past decade. Although she has had several "abnormal Pap tests" in the past, she states she has never needed treatment. She was found to have a dense acetowhite (AW) lesion on colposcopy that was biopsied (Figure 92-1). The pathology returned high grade consistent with cervical intraepithelial neoplasia grade 3 (CIN 3), and the patient was treated with loop electrosurgery. She had negative margins on the loop electrosurgical excision procedure specimen and remained recurrence-free at 3 years.


Dense acetowhite (white after application of vinegar) lesions with "rolled" edges in a patient with high-grade disease. Her colposcopically directed biopsies showed cervical intraepithelial neoplasia grade 3. (Reproduced with permission from E.J. Mayeaux, Jr., MD.)


High-grade squamous intraepithelial lesions in adult women are considered true cancer precursors because if left untreated, they have a significant chance of developing into invasive cancer.


Cervical intraepithelial neoplasia (CIN 3 and CIN 2) are high-grade lesions.


  • Overall rates of Pap test abnormalities are usually estimated from local or regional studies. For example, in an observational cohort study of routine cervical tests in the northwestern United States, in women of all ages (n = 150,052), high-grade squamous intraepithelial lesion was diagnosed at a rate of 0.8 per 1000 compared to negative routine tests that were diagnosed at a rate of 278.5 per 1000.1

  • In HPV vaccine age groups, there were significant reductions in the CIN incidence per 100,000 women screened for all grades of CIN. In female individuals 15 to 19 years old, the incidence dropped from 3468.3 to 1590.6 for CIN 1 per 100,000, from 896.4 to 414.9 for CIN 2, and from 240.2 to 0 for CIN 3 per 100,000.2


  • In high-grade squamous intraepithelial lesions, the abnormalities are immature parabasilar cell types. They have an increased nuclear-to-cytoplasmic ratio, enlarged hyperchromatic nucleoli, few nucleoli, and a reticular or granular appearance.

  • On histology, abnormal maturation and nuclear atypia defines CIN. Koilocytosis (perinuclear cytoplasmic vacuolization) is indicative of human papillomavirus (HPV) infection and may be found with high-grade CIN. High-grade CIN is diagnosed when immature basaloid cells with nuclear atypia occupy more than the lower one third of the epithelium. With increasing lesion severity there is also increased nuclear crowding, pleomorphism, normal and abnormal mitosis, and loss of polarity.3

  • Traditionally, high-grade CIN had been thought to arise as a small focus within a larger area of low-grade CIN that expands and eventually replaces much of the low-grade lesion.

  • It is now thought that high-grade ...

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