GRADE 2 CIN

Nearly Half of Grade 2 Cervical Intraepithelial Neoplasias Will Regress

NEW YORK (Reuters Health) Jan 05 - Approximately 40% of cervical intraepithelial neoplasia grade 2 (CIN2) will regress within 2 years, according to a study published in the January issue of Obstetrics and Gynecology.

However, the same study found that CIN2 caused by human papillomavirus type 16 (HPV-16) is much less likely to regress.

Dr. Philip E. Castle of the National Cancer Institute in Bethesda and colleagues used data from the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS) to compare the cumulative incidences of CIN2, CIN3 or more severe diagnoses in the 2-year study.

ALTS was a multicenter, randomized trial comparing three management strategies for women referred for atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL).

The study population consisted of 3,488 women with ASC-US and 1,572 women with LSIL. There were 397 cases of CIN2 and 542 cases of CIN3 or more severe disease.

The three strategies were immediate colposcopy, HPV triage, or conservative management. In the HPV triage arm, women were referred to immediate colposcopy if they were HPV-positive at enrollment, if there was no information on HPV status at enrollment, or if cytology showed high-grade squamous intraepithelial lesion (HSIL) at enrollment.

Dr. Castle and associates report no significant difference in the cumulative 2-year incidence of CIN3 or more severe disease between the study arms. The rate was 10.9% with conservative management, 10.3% with HPV triage and 10.9% with immediate colposcopy.

In contrast, there was a significant variation in the 2-year incidence of CIN2 between treatment arms. CIN2 incidence was 5.8% for women assigned to conservative management, 7.8% for women assigned to HPV triage, and 9.9% for women assigned to immediate colposcopy.

During the 2-year study period, there was an increasing number of women with CIN2 referred to colposcopy at baseline. The relative differences in incidence of CIN2, by study arm, among women who tested HPV-16 positive at baseline were less pronounced than women who tested positive for other high-risk-HPV genotypes.

"Nearly half of all CIN2, a diagnosis that is considered a precancerous diagnosis and is treated by excisional procedures, will regress without treatment, (although) CIN2 caused by HPV-16 is less likely to regress," Dr. Castle told Reuters Health.

"Thus, many women with CIN2 are being treated for benign lesions that are probably not precancerous. Because treatment has negative reproductive consequences (e.g., preterm delivery), improved management strategies for CIN2 to reduce unnecessary treatment while still identifying and treating women with precancerous lesions are needed."

"HPV-16-positive CIN2 seems less likely to regress, perhaps as the result of its greater tendency to persist and its greater oncogenic potential to progress to precancerous lesions than other HPV genotypes," Dr. Castle and colleagues write.

"When HPV genotyping from validated tests becomes routinely available, detection of HPV-16 may be a useful stratifier of risk for deciding the clinical management of CIN2 diagnoses."

"A clinical trial to determine the best management strategies for CIN2, akin to ALTS for ASC-US and LSIL Pap tests, is needed," they add.