Effect of several negative rounds of human papillomavirus and cytology co-testing on safety against cervical cancer

Philip E. Castle, Walter K. Kinney, Xiaonan Xue, Li C. Cheung, Julia C. Gage, Fang Hui Zhao, Barbara Fetterman, Nancy E. Poitras, Thomas S. Lorey, Nicolas Wentzensen, Hormuzd A. Katki, Mark Schiffman

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Background: 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. Objective: To measure cervical cancer risk in routine practice after successive negative screening co-tests at 3-year intervals. Design: Observational cohort study. Setting: Integrated health care system (Kaiser Permanente Northern California, Oakland, California). Patients: 990 013 women who had 1 or more co-tests from 2003 to 2014. Measurements: 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. Results: 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. Limitation: Interval-censored observational data. Conclusion: After 1 or more negative cervical co-tests (or HPV tests), longer screening intervals (every 5 years or more) might be feasible and safe.

Original languageEnglish (US)
Pages (from-to)20-29
Number of pages10
JournalAnnals of internal medicine
Issue number1
StatePublished - Jan 2 2018

ASJC Scopus subject areas

  • Internal Medicine


Dive into the research topics of 'Effect of several negative rounds of human papillomavirus and cytology co-testing on safety against cervical cancer'. Together they form a unique fingerprint.

Cite this