Negative human papillomavirus test predicts low precancer
After a negative human papillomavirus test, long-term risk of treatable cervical precancer stayed very low, and adding cytology offered little extra benefit.
*Linked cohort study from trial to registry; Level 2b (OCEBM).

Citation

Gottschlich A, Smith LW, Hong Q, et al. Human papillomavirus, cytology, and cotest cervical cancer screening and the risk of precancer. JAMA Network Open. 2026;9(3):e261304. doi:10.1001/jamanetworkopen.2026.1304

Background

Many programs are shifting from microscope-based cell examination (cytology) to human papillomavirus testing for cervical cancer screening. Whether combining both tests meaningfully improves long-term safety remains uncertain.

Patients

8078 routinely screened women in British Columbia who completed exit screening with both tests; median age 49 years. Excluded: trial control-group participants who did not complete exit cotesting. Screening (not symptomatic) population.

Intervention

Primary human papillomavirus screening strategy (modeled as a negative human papillomavirus result regardless of cytology).

Control

Cotesting strategy (both tests negative) and cytology strategy (normal cytology regardless of human papillomavirus result).

Outcome

Cumulative risk of cervical precancer at the treatment threshold (grade 2 or worse).

Follow-up Period

Up to 10 years after exit screening (median 6.6 years).

Results

Exit screening result group 9-year risk of treatable precancer Extra diagnostic procedures needed to find 1 case (vs both tests negative)
Human papillomavirus negative (any cytology) 0.41% —
Both tests negative 0.37% Reference
Normal cytology (any human papillomavirus result) 1.28% —
Human papillomavirus negative + abnormal cytology 4.83% 25
Human papillomavirus positive + normal cytology 22.21% 8
Human papillomavirus positive + abnormal cytology 43.47% 3
In women aged 60–69 years who were human papillomavirus negative at exit screening, no treatable precancers were found during follow-up.

Limitations

Observational follow-up of a selected trial subgroup, not a newly randomized comparison. Older participants could stop routine screening near age 69, limiting later outcome capture. Findings do not apply to symptomatic patients.

Funding

National Institutes of Health; Canadian Institutes for Health Research; Michael Smith Foundation.

Clinical Application

For routine screening, a negative human papillomavirus test supports longer intervals; adding cytology appears to add little benefit while increasing follow-up procedures and cost.