Philip E. Castle, PhD, MPH; Walter K. Kinney, MD *; Xiaonan Xue, PhD; Li C. Cheung, PhD; Julia C. Gage, PhD, MPH; Fang-Hui Zhao, MD; Barbara Fetterman, BS; Nancy E. Poitras, BS; Thomas S. Lorey, MD; Nicolas Wentzensen, MD, PhD, MS; Hormuzd A. Katki, PhD; Mark Schiffman, MD, MPH
Grant Support: Dr. Castle was supported in part by an Intergovernmental Personnel Act assignment from the National Institutes of Health/National Cancer Institute.
Disclosures: Dr. Castle reports receiving cervical screening tests and diagnostics from Roche, BD Biosciences, Cepheid, and Arbor Vita at reduced or no cost for research. Drs. Gage, Wentzensen, and Schiffman are employed by the National Cancer Institute, which has received cervical cancer screening assays in kind or at reduced cost from BD Biosciences, Cepheid, Hologic, and Roche. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-1609.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol and statistical code: Available from Dr. Castle (e-mail, email@example.com). Data set: Not available.
Requests for Single Reprints: Philip E. Castle, PhD, MPH, 1300 Morris Park Avenue, Belfer Building, Room 1308C, Bronx, NY 10461; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Castle: 1300 Morris Park Avenue, Belfer Building, Room 1308C, Bronx, NY 10461.
Dr. Kinney: 2589 Garden Highway, Sacramento, CA 95833.
Dr. Xue: 1300 Morris Park Avenue, Room 1303C, Bronx, NY 10461.
Dr. Cheung: Room 7E612, 9609 Medical Center Drive, Rockville, MD 20850.
Dr. Gage: Room 6E546, 9609 Medical Center Drive, Rockville, MD 20850.
Dr. Zhao: Cancer Institute/Hospital, Chinese Academy of Medical Sciences, 17 South Panjiayuan Lane, PO Box 2258, Beijing 100021, China.
Ms. Fetterman: TPMG Regional Laboratory, Cytology Department, 1725 Eastshore Highway, Berkeley, CA 94710.
Ms. Poitras: Kaiser Permanente, 501 Lennon Lane, Walnut Creek, CA 94597.
Dr. Lorey: Kaiser Permanente Regional Laboratories, 1725 Eastshore Highway, Berkeley, CA 94710.
Dr. Wentzensen: Room 6E448, 9609 Medical Center Drive, Rockville, MD 20850.
Dr. Katki: Room 7E606, 9609 Medical Center Drive, Rockville, MD 20850.
Dr. Schiffman: Room 6E544, 9609 Medical Center Drive, Rockville, MD 20850.
Author Contributions: Conception and design: P.E. Castle, L.C. Cheung, J.C. Gage, T.S. Lorey, M. Schiffman.
Analysis and interpretation of the data: P.E. Castle, X. Xue, L.C. Cheung, J.C. Gage, F.-H. Zhao, N.E. Poitras, N. Wentzensen, H.A. Katki, M. Schiffman.
Drafting of the article: P.E. Castle, W.K. Kinney, L.C. Cheung, J.C. Gage, F.-H. Zhao, H.A. Katki, M. Schiffman.
Critical revision for important intellectual content: P.E. Castle, L.C. Cheung, J.C. Gage, N. Wentzensen, H.A. Katki, M. Schiffman.
Final approval of the article: P.E. Castle, W.K. Kinney, X. Xue, L.C. Cheung, J.C. Gage, F.-H. Zhao, B. Fetterman, N.E. Poitras, T.S. Lorey, N. Wentzensen, H.A. Katki, M. Schiffman.
Statistical expertise: P.E. Castle, X. Xue, L.C. Cheung, H.A. Katki.
Obtaining of funding: M. Schiffman.
Administrative, technical, or logistic support: T.S. Lorey, M. Schiffman.
Collection and assembly of data: P.E. Castle, W.K. Kinney, B. Fetterman, N.E. Poitras, M. Schiffman.
Current U.S. cervical cancer screening and management guidelines do not consider previous screening history, because data on multiple-round human papillomavirus (HPV) and cytology “co-testing” have been unavailable.
To measure cervical cancer risk in routine practice after successive negative screening co-tests at 3-year intervals.
Observational cohort study.
Integrated health care system (Kaiser Permanente Northern California, Oakland, California).
990 013 women who had 1 or more co-tests from 2003 to 2014.
3- and 5-year cumulative detection of (risk for) cervical intraepithelial neoplasia grade 3, adenocarcinoma in situ, and cervical cancer (≥CIN3) in women with different numbers of negative co-tests, overall and within subgroups defined by previous co-test results or baseline age.
Five-year ≥CIN3 risks decreased after each successive negative co-test screening round (0.098%, 0.052%, and 0.035%). Five-year ≥CIN3 risks for an HPV-negative co-test, regardless of the cytology result, nearly matched the performance (reassurance) of a negative co-test for each successive round of screening (0.114%, 0.061%, and 0.041%). By comparison, ≥CIN3 risks for the cytology-negative co-test, regardless of the HPV result, also decreased with each successive round, but 3-year risks were as high as 5-year risks after an HPV-negative co-test (0.199%, 0.065%, and 0.043%). No interval cervical cancer cases were diagnosed after the second negative co-test. Independently, ≥CIN3 risks decreased with age. Length of previous screening interval did not influence future ≥CIN3 risks.
Interval-censored observational data.
After 1 or more negative cervical co-tests (or HPV tests), longer screening intervals (every 5 years or more) might be feasible and safe.
National Cancer Institute Intramural Research Program.
Castle PE, Kinney WK, Xue X, Cheung LC, Gage JC, Zhao F, et al. Effect of Several Negative Rounds of Human Papillomavirus and Cytology Co-testing on Safety Against Cervical Cancer: An Observational Cohort Study. Ann Intern Med. ;168:20–29. doi: 10.7326/M17-1609
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Published: Ann Intern Med. 2018;168(1):20-29.
Published at www.annals.org on 28 November 2017
Hematology/Oncology, High Value Care.
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