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Yield and Mode of Diagnosis of Cervical Intraepithelial Neoplasia 3 or Cancer Among Women With Negative Cervical Cytology and Positive High-Risk Human Papillomavirus Test Results

Pretorius, Robert G. MD1; Belinson, Jerome L. MD2; Peterson, Patricia1; Azizi, Famaraz MD3; Lo, Andrew MD3

Journal of Lower Genital Tract Disease: October 2013 - Volume 17 - Issue 4 - p 430–439
doi: 10.1097/LGT.0b013e318281f182
Original Articles

Objective In women with negative cervical cytology and positive high-risk human papillomavirus (HR-HPV) test results, we compared the risk of cervical intraepithelial neoplasia 3 (CIN 3) or cancer (CIN 3+) in women with previous abnormal cervical cytology, CIN, or HR-HPV with that in women without this history, and we determined their cumulative risk of CIN 3+.

Materials and Methods We reviewed colposcopies for negative cytology and positive HR-HPV test results from 2007 to 2009 (colposcopy was done for previous abnormal cytology, HR-HPV, or CIN or if negative cytology and positive HR-HPV test results for 20–35 months). Women with negative cytology and positive HR-HPV test results in 2007 were reviewed to determine their cumulative risk of CIN 3+.

Results Of the 513 women with colposcopy for negative cytology and positive HR-HPV test results, 367 had previous abnormal cytology, CIN, or HR-HPV greater than 35 months ago and 146 had negative cytology and positive HR-HPV test results for 20 to 35 months. Risk of CIN 3+ for women with negative cytology and positive HR-HPV test results with previous abnormal cytology, HR-HPV, or CIN who did not have previous colposcopy was 11.9% (8/67); for similar women with previous colposcopy, it was 2.7% (8/300); and for women with positive HR-HPV test result for 20 to 35 months, it was 7.5% (11/146). In 2007 to 2009, risk of CIN 3+ for women with cytology of atypical squamous cells of undetermined significance (ASC-US) with positive HR-HPV test result was 3.9% (60/1,540). Of the 1,726 women with negative cytology and positive HR-HPV test result in 2007, 381 (22.1%) were lost to follow-up. Of the 1,345 women with median follow-up of 44 months, 602 (44.8%) had 1 or 2 subsequent negative cytology and negative HR-HPV test results and 180 had subsequent positive HR-HPV test result without biopsy. Of the 563 women with biopsy, there were 711 evaluations. Invasive cancer was found in 4 and CIN 3 in 54 (cumulative CIN 3+ of 4.3%, 58/1,345). Half (29/58) of the cumulative CIN 3+ was diagnosed after subsequent abnormal cytology and positive HR-HPV test result.

Conclusions If referral to colposcopy of women with cervical cytology of ASC-US and positive HR-HPV test result (CIN 3+, 3.9%) is justified, referral to colposcopy of women with negative cytology and positive HR-HPV test results is justified if they have previous abnormal cervical cytology, CIN, or HR-HPV greater than 35 months ago but have not had previous colposcopy (CIN 3+=11.9%) or are persistently HR-HPV positive for 20 to 35 months (CIN 3+, 7.5%). The risk of CIN 3+ in women with previous abnormal cytology, CIN, or HR-HPV who have previous colposcopy (2.7%) is lower because these women have incident rather than prevalent CIN 3+.

Women with negative cytology and positive HR-HPV test results should be referred for colposcopy if they have previous abnormal cervical cytology, CIN, or HR-HPV greater than 35 months ago but have not had previous colposcopy or are persistently HR-HPV positive for 20 to 35 months.

1Department of Obstetrics and Gynecology, Southern California Permanente Medical Group–Fontana, Fontana, CA; 2Department of Gynecology, The Cleveland Clinic Foundation, Cleveland, OH; and 3Department of Pathology, Southern California Permanente Medical Group–Fontana, Fontana, CA

Reprint requests to: Robert G. Pretorius, MD, Southern California Permanente Medical Group–Fontana, Department of Obstetrics and Gynecology, 9961 Sierra Ave, Fontana, CA 92335. E-mail: Robert.G.Pretorius@kp.org

The authors have declared they have no conflicts of interest.

Copyright © 2013 by the American Society for Colposcopy and Cervical Pathology