New longitudinal data suggest that adding cytology to primary human papillomavirus (HPV) testing provides limited additional benefit in cervical cancer screening, while increasing complexity and cost.
In a cohort study published in JAMA Network Open, researchers found that women with a negative HPV test had a very low long-term risk of cervical precancer, regardless of cytology results. Over a decade of follow-up, with most estimates reported at nine years, this risk was comparable to that seen in women who were negative on both HPV and cytology testing.
CLINICAL SUMMARY
What was examined
A longitudinal cohort study linked to the HPV FOCAL randomised trial assessed the long-term risk of cervical precancer following HPV testing, cytology, or HPV–cytology co-testing in 8078 women undergoing cervical screening.
Key findings
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Women with a negative HPV test had a very low long-term risk of CIN2+ (0.41% over nine years), similar to those with negative co-testing (0.37%).
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Risk was higher in women with normal cytology regardless of HPV status (1.28%).
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HPV-negative women with abnormal cytology were rare (<1% of the cohort) and accounted for only three of the 100 precancer cases detected.
Clinical implications
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Primary HPV screening alone appears sufficient for identifying women at low risk of cervical precancer.
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Adding cytology to HPV testing provides a limited incremental benefit while increasing costs and follow-up procedures.
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These findings support the continued shift toward primary HPV-based cervical screening programs.
The findings add to growing evidence supporting primary HPV testing as the most efficient strategy for cervical cancer screening, as many countries transition away from cytology-based programs.
Cervical cancer remains largely preventable through vaccination and screening, yet more than 300,000 women worldwide die from the disease each year. As part of global efforts to eliminate cervical cancer as a public health problem, health systems are reassessing optimal screening approaches.
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Historically, cytology (Pap testing) formed the basis of screening programs. However, HPV testing is more sensitive for detecting cervical precancer. Some programs have adopted co-testing—HPV testing combined with cytology—despite uncertainty about whether the additional test meaningfully improves outcomes.
To examine this question, investigators analysed data from the HPV FOCAL randomised trial and its linked long-term follow-up cohort (FOCAL-DECADE) in British Columbia, Canada. The study included 8078 women who underwent HPV and cytology co-testing at trial exit and were followed through a provincial screening registry capturing all cervical screening and follow-up procedures.
Participants had a median age of 49 years at exit screening.
During follow-up, the risk of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) varied substantially according to HPV status.
Women who were HPV-positive with abnormal cytology had the highest cumulative risk of precancer over nine years (43.5%), followed by those who were HPV-positive but cytology-negative (22.2%). In contrast, risk remained low among HPV-negative women, including those with abnormal cytology.
Among women who were HPV-negative regardless of cytology result, the cumulative incidence of CIN2+ after nine years was 0.41%. This was very similar to the risk among women who were negative on both tests (0.37%), but lower than the risk among those with normal cytology regardless of HPV status (1.28%).
Notably, fewer than 1% of participants were HPV-negative with abnormal cytology, and this group accounted for only three of the 100 CIN2+ cases detected during follow-up.
The authors estimated that 25 additional colposcopies would be required in HPV-negative women with abnormal cytology to detect one extra precancer compared with co-test-negative screening.
The findings were consistent across age groups. Among women aged 60–69 years who tested HPV-negative, no precancer cases were detected during follow-up.
Importantly, the study also found that the risk of precancer nine years after a negative HPV test was similar to the risk observed three years after a normal cytology screen. Because cytology-based screening has traditionally been performed at three-year intervals, the authors suggest this supports longer screening intervals following a negative HPV result.
Taken together, the results suggest that cytology provides limited incremental benefit when HPV testing is already used as the primary screening method. Because co-testing requires additional laboratory resources and clinical follow-up, its use may increase costs without substantially improving detection rates, according to the authors.
The authors note that cytology may still have a role in diagnostic assessment of symptomatic patients, but in population screening programs, the added value appears limited.
As more countries adopt primary HPV screening—including Australia, which transitioned in 2017—the findings provide further support for streamlined screening strategies focused on HPV detection.
Paper: Gottschlich. et al. HPV, Cytology, and Cotest Cervical Cancer Screening and the Risk of Precancer. JAMA Network Open. 2026;9(3):e261304. doi:10.1001/jamanetworkopen.2026.1304. Access online here.
