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Int J Cancer. 2019 Mar 12. doi: 10.1002/ijc.32268. [Epub ahead of print]

Absolute risks of cervical precancer among women who fulfill exiting guidelines based on HPV and cytology cotesting.

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Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD, USA.
Faculty of Life Sciences & Medicine, School of Cancer & Pharmaceutical Sciences, Guys Cancer Centre, Guys Hospital, King's College London, London, SE1 9RT, United Kingdom.
Information Management Services Inc., Calverton, MD, USA.
Regional Laboratory, Kaiser Permanente Northern California, Berkeley, CA, USA.
Division of Gynaecologic Oncology, Kaiser Permanente Medical Care Program, Oakland, CA, USA.
Albert Einstein College of Medicine, Bronx, NY, USA.


US guidelines recommend that most women older than 65 years cease cervical screening after two consecutive negative cotests (concurrent HPV and cytology tests) in the previous 10 years, with one in the last 5 years. However, this recommendation was based on expert opinion and modeling rather than empirical data on cancer risk. We therefore estimated the 5-year risks of cervical precancer (cervical intraepithelial neoplasia grade 3 or adenocarcinoma in situ [CIN3]) after one, two and three negative cotests among 346,760 women aged 55-64 years undergoing routine cotesting at Kaiser Permanente Northern California (2003-2015). Women with a history of excisional treatment or CIN2+ were excluded. No woman with one or more negative cotests was diagnosed with cancer during follow-up. Five-year risks of CIN3 after one, two, and three consecutive negative cotests were 0.034% (95% CI: 0.023%-0.046%), 0.041% (95% CI: 0.007%-0.076%) and 0.016% (95% CI: 0.000%-0.052%), respectively (ptrend < 0.001). These risks did not appreciably differ by a positive cotest result prior to the one, two or three negative cotest(s). Since CIN3 risks after one or more negative cotests were significantly below a proposed 0.12% CIN3+ risk threshold for a 5-year screening interval, a longer screening interval in these women is justified. However, the choice of how many negative cotests provide sufficient safety against invasive cancer over a woman's remaining life represents a value judgment based on the harms versus benefits of continued screening. Ideally, this guideline should be informed by longer-term follow-up given that exiting is a long-term decision.


HPV; cervical cancer; cervical screening; cotesting; exiting; guidelines


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