Objective: Most women referred for colposcopy are not diagnosed with cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) but, nonetheless, are typically asked to return much sooner than their next routine screening interval in 3 to 5 years. An important question is how many subsequent negative Pap results, or negative Pap and human papillomavirus (HPV) cotest results, are needed before returning to an extended retesting interval.
Methods: We estimated 5-year risks of CIN 2+ for 3 follow-up management strategies after colposcopy (Pap-alone, HPV-alone, and cotesting) for 20,319 women aged 25 years and older screened from 2003 to 2010 at Kaiser Permanente Northern California who were referred for colposcopy but for whom CIN 2+ was not initially diagnosed (i.e., “women with CIN 1/negative colposcopy”).
Results: Screening results immediately antecedent to CIN 1/negative colposcopy influenced subsequent 5-year CIN 2+ risk: women with an antecedent HPV-positive/atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) Pap had a lower risk (10%) than those with antecedent atypical squamous cells cannot rule out HSIL (ASC-H; 16%, p < .0001) or high-grade squamous intraepithelial lesion or worse (HSIL+; 24%, p < .0001). For women with an antecedent HPV-positive/ASC-US or LSIL, a single negative cotest approximately 1 year after colposcopy predicted lower subsequent 5-year risk of CIN 2+ (1.1%) than 2 sequential negative HPV tests (1.8%, p = .3) or 2 sequential negative Pap results (4.0%, p < .0001). For those with an antecedent ASC-H or HSIL+ Pap, 1 negative cotest 1 year after colposcopy predicted lower subsequent 5-year risk of CIN 2+ (2.2%) than 1 negative HPV test (4.4%, p = .4) or 1 negative Pap (7.0%, p = .06); insufficient data existed to calculate the risk after sequential negative cotests for women with high-grade antecedent cytology.
Conclusions: Women with a CIN 1/negative colposcopy followed by negative postcolposcopy tests did not achieve sufficiently low CIN 2+ risk to return to 5-year routine screening. For women with antecedent HPV-positive/ASC-US or LSIL, a single negative postcolposcopy cotest reduced their risk to a level consistent with a 3-year return. For women with antecedent ASC-H or HSIL+, no single negative test result sufficed to reduce their risk to a level consistent with a 3-year return.
For women with CIN 1/negative colposcopy and antecedent HPV-positive/ASC-US or LSIL, a single negative postcolposcopy cotest reduced the risk to a level consistent with a 3-year return.
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: email@example.com; Walter K. Kinney, MD, Kaiser Permanente Northern California, Sacramento Medical Center, 1650 Response Rd, Sacramento, CA 95815. E-mail: firstname.lastname@example.org
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 at no cost. 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.