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Risk of Developing CIN3 in Women with ASCUS or LSIL

Am Fam Physician. 2006 Nov 15;74(10):1782-1784.

Each year, approximately 2 to 3 million women in the United States have abnormal cervical cytology indicating an increased risk of cervical cancer. A significant portion of women who are found to have cervical intra-epithelial neoplasia (CIN) 3 on biopsy had an original diagnosis of human papillomavirus (HPV)–positive atypical squamous cells (ASC) or low-grade squamous intraepithelial lesions (LSIL). Women who have findings of less than CIN2 at their first colposcopy for HPV-positive ASC or LSIL still are at risk of developing more severe disease in the next few years. Follow-up guidelines for these women are repeat cytology at six and 12 months or high-risk HPV testing at 12 months. If there is an abnormality on either of these tests, repeat colposcopy should be preformed. Walker and colleagues evaluated the absolute risk of developing CIN 2 or CIN3 within two years in women found to have less than CIN2 on colposcopy.

The authors conducted a prospective evaluation of women with atypical squamous cells of undetermined significance (ASCUS) or LSIL cervical cytology on colposcopy-directed biopsies enrolled in the ASCUS-LSIL Triage Study. Analysis was restricted to women who had ASCUS or LSIL on a Papanicolaou (Pap) smear within the previous six months, were found to have less than CIN2 on biopsy, and were followed without treatment. All women had repeat Pap smears every six months and repeat colposcopy two years after the initial evaluation. HPV testing also was performed during the follow-up period. Women with high-grade squamous intraepithelial lesions (HSIL) on Pap smear were immediately referred for colposcopy. The absolute risk of developing CIN3 was calculated from the colposcopy findings.

There were 1,976 women included in the analysis. Fort-eight percent were positive for HPV. The absolute risk of developing CIN3 in two years in women with a positive HPV test result was 12 percent; for women without HPV, it was 2 percent. Normal repeat cytology results had an absolute risk of developing CIN3 of 3.1 percent; with a result of ASCUS, the risk was 7.9 percent; with LSIL, the risk was 9.2 percent; and with HSIL, the risk was significantly elevated at 42 percent. In women with a positive HPV test result, the risk was higher for each category compared with those who had a negative result. Women with negative HPV test results were at low risk of CIN3 regardless of the other test results. Women with positive HPV test results, HSIL cytology, and colposcopic impression of high grade or cancer had an increased absolute risk of 67 percent.

The authors conclude that colposcopy-directed biopsies do not detect all lesions greater than CIN2 in women with ASCUS or LSIL cytology. HPV testing alone is more sensitive than repeat cytology, but in this study, it referred 48 percent to colposcopy. The authors add that the presence of HPV, HSIL, and high-grade impression or cancer on colposcopy was the best predictor of advanced cervical lesions. This information could be used to guide treatment of select women who met this criteria at the time of the colposcopy (a “see and treat” approach), especially if compliance is a concern.

Walker JL, et al. Predicting absolute risk of CIN3 during post-colposcopic follow-up: results from the ASCUS-LSIL Triage Study (ALTS). Am J Obstet Gynecol. August 2006;195:341–8.


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