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Five-Year Risk of CIN 3+ to Guide the Management of Women Aged 21 to 24 Years

Katki, Hormuzd A. PhD1; Schiffman, Mark MD, MPH1; Castle, Philip E. PhD, MPH2; Fetterman, Barbara SCT (ASCP)3; Poitras, Nancy E. PMP3; Lorey, Thomas MD3; Cheung, Li C. MS4; Raine-Bennett, Tina MD, MPH5; Gage, Julia C. PhD, MPH1; Kinney, Walter K. MD6

Journal of Lower Genital Tract Disease: April 2013 - Volume 17 - Issue - p S64–S68
doi: 10.1097/LGT.0b013e3182854399
Original Article

Objective Current US national guidelines recommend beginning screening at age 21 using Pap tests only, with cotesting starting at age 30. To inform the management of Pap test abnormalities among women aged 21 to 24 years, who have extremely low cancer risks, we compared risks of CIN 3+ among women aged 21 to 24 versus 25 to 29 years or 30 to 64 years.

Methods We estimated 5-year risks of CIN 3+ given different Pap test results, with human papillomavirus (HPV) triage of atypical squamous cells of undetermined significance (ASC-US), among 133,947 women aged 21 to 24 years, compared with 135,382 women aged 25 to 29 years and 965,360 women aged 30 to 64 years, between 2003 and 2010 at Kaiser Permanente Northern California.

Results There were 3 cancers diagnosed during follow-up in women aged 21 to 24 years. After high-grade Pap results (0.6% of Pap results), the 5-year CIN 3+ risks among women aged 21 to 24 years were comparable to those aged 25 to 29 and 30 to 64 years (atypical glandular cells, 6.9% vs 14% vs 8.5%, p = .8; atypical squamous cells cannot rule out high-grade squamous intraepithelial lesion, 16% vs 24% vs 18%, p = .8; high-grade squamous intraepithelial lesion, 28% vs 28% vs 47%, p = .4). After low-grade squamous intraepithelial lesion, the 5-year CIN 3+ risk was lower among women aged 21 to 24 years (3.0%) than that among women aged 25 to 29 years (5.0%, p = .01) or aged 30 to 64 years (5.2%, p = .0002). Although the 5-year CIN 3+ risk after HPV-negative/ASC-US was similar across all 3 groups (0.57% vs 0.59% vs 0.43%, p = 1), risk after HPV-positive/ASC-US was lower among women aged 21 to 24 years (4.4%) than that among women aged 25 to 29 years (7.1%, p < .0001) or 30 to 64 years (6.8%, p < .0001).

Conclusions Women aged 21 to 24 years had almost zero cancer risk, and positive Pap test results predicted low CIN 3+ risk except for the 0.6% of women with high-grade Pap results. The generally low risk supports conservative management of women aged 21 to 24 years.

The finding of extremely low risk for cancer and low risk for CIN 3 among women aged 21 to 24 years supports conservative management of abnormal screening results in this age group.

1Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD; 2Albert Einstein College of Medicine, Bronx, NY; 3Regional Laboratory, Kaiser Permanente Northern California, Berkeley, CA; 4Information Management Services, Inc, Calverton, MD; 5Women’s Health Research Institute, Division of Research, Kaiser Permanente Northern California, Oakland, CA; and 6Division of Gynecologic Oncology, Kaiser Permanente Medical Care Program, Oakland, CA

Reprint requests to: Hormuzd A. Katki, PhD, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd Room 8014, EPS MSC 7244, Bethesda, MD 20882. E-mail:; Walter K. Kinney, MD, Kaiser Permanente Northern California, Sacramento Medical Center, 1650 Response Rd, Sacramento, CA 95815. E-mail:

Drs Schiffman and Gage report working with Qiagen, Inc, on an independent evaluation of noncommercial uses of CareHPV (a low-cost human papillomavirus [HPV] test for low-resource regions) for which they have received research reagents and technical aid from Qiagen for free. They have received HPV testing for research at no cost from Roche. Dr Castle has received compensation for serving as a member of a Data and Safety Monitoring Board for HPV vaccines for Merck and also received HPV tests and testing for research at a reduced or no cost from Qiagen, Roche, MTM, and Norchip. Dr Castle is a paid consultant for BD, GE Healthcare, and Cepheid and has received a speaker honorarium from Roche. The other authors have declared they have no conflicts of interest.

The Intramural Research Program of the US National Institutes of Health/National Cancer Institute and Kaiser Permanente Northern California reviewed the final article for publication. The Kaiser Permanente Northern California Institutional Review Board (IRB) approved use of the data, and the National Institutes of Health Office of Human Subjects Research deemed this study exempt from IRB review.

©2013The American Society for Colposcopy and Cervical Pathology