What Is CIN 2 and How Should It Be Treated? : The debate over whether cervical intraepithelial neoplasia grade 2 is a real, distinct entity continues.


LAS VEGAS — Experts are divided on how aggressively cervical intraepithelial neoplasia grade 2 should be treated, and on whether observation is an acceptable option, especially in low-risk populations.

Cervical intraepithelial neoplasia (CIN) has been regarded as a preinvasive condition, with progressively higher grades being associated with an increasing risk of cancer. As most CIN 1 lesions regress without treatment, it has been suggested that CIN 2 may also have limited potential to progress to a more invasive disease.

“The goal of treatment for CIN is to prevent cancer by eliminating lesions with true malignant potential,” Dr. Mark Spitzer said at a meeting of the American Society for Colposcopy and Cervical Pathology. “And we also want to avoid unnecessary treatment of lesions with little or no premalignant potential.”

The data are mixed, said Dr. Spitzer of New York University, New York. Some studies show that CIN 2 is an intermediate entity that lies between CIN 1 and CIN 3 and has some premalignant potential although not as great as that of CIN 3. Other studies show that it is much closer to CIN 1 or benign disease, so it does not have real premalignant potential.

That raises the question, “Is the diagnosis of CIN 2 a reliable or reproducible diagnosis?” Dr. Spitzer said.

He pointed out that a few studies have assessed that question, and one concluded that interobserver variation is fair to good for the diagnosis of benign conditions, CIN 3, or invasive cancer, but poor for the diagnosis of CIN 1 or CIN 2. There is also poorer correlation between colposcopic and histologic diagnosis with CIN 2, compared with CIN 1 and CIN 3.

“The problem with CIN 2 is that we don't really know what it is,” Dr. Spitzer said. Any system of grading an intraepithelial lesion, in which there is a lesional continuum, is essentially artificial. A grading system that is based on light microscopy is subject to inter- and intraobserver variations in reporting, and treating all patients with CIN 2 will clearly result in the overtreatment of many of them.

There's also a question of age, when making the decision to treat cervical lesions. CIN 2 in adolescents is different than it is in adults, he explained. Some preliminary results showed that after 1 year, the behavior of CIN 2 in adolescents was the same as that of CIN 1.

“If you're under 20 the risk of invasive cancer is zero,” said Dr. Spitzer. “If you're in the cohort under age 25, it still is really very low. So not treating CIN 2 in younger patients really makes a lot of sense.”

However, Dr. Edward John Mayeaux Jr., an associate professor of family medicine and obstetrics and gynecology at Louisiana State University, Shreveport, disagreed with the assumption that CIN 2 isn't a real entity. “This has been debated before,” he said, “And the data do show that it is different in its progression and regression potential than CIN 1. It has a biological activity that is different from both CIN 1 and CIN 3.

“In adolescents it is often transient and the risk of cancer is small, and our guidelines already say that observation for 1 year is acceptable for adolescents with CIN 2,” Dr. Mayeux said.

Dr. Mayeaux also pointed out that in the United States, CIN 2 and 3 are managed in a similar fashion, primarily because the potential for progression is higher than that of CIN 1 and reliable histologic differentiation in CIN 2 and 3 is only moderate.

Overall, CIN 3 has about a 12% progression to cancer, but CIN 2 has about a 5% progression to cancer. These estimates do vary significantly, and at this time, most authors, guidelines, and professional organizations do recommend treatment for both CIN 2 and 3 lesions.

“We do need a better way to tell who is going to progress, and I agree with that,” said Dr. Mayeaux. “The difference in our point of view is that I don't think we're there yet. And until we get there, we don't know what those changes are going to mean for patient outcome. We still need to treat it until we reach that point.”

Given the current variations in equipment and practice, and the greater potential of CIN 2 to progress, compared with CIN 1, Dr. Mayeaux recommends no changes in current treatment protocols.

In rebuttal, Dr. Spitzer pointed out that while there is no doubt that CIN 2 has some premalignant potential, overtreatment with the loop electrosurgical excision procedure can also have consequences.

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