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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.

Top Journal Rankings - May 2026

10 abstracts scored across 7 criteria. Click any article to expand criterion scores.
1. 7.5
Do Vitreous Floaters Predict Retinal Detachment? Retrospective Cohort Study in Primary Care.
Overall: A primary-care retrospective cohort provides actionable absolute and relative risks linking new-onset floaters to retinal detachment, with good real-world applicability but only moderate certainty due to observational EHR limitations and incomplete data on downstream harms of changing referral behavior.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 9.0
Conducted in 7 family practices with typical primary-care presentations (new-onset floaters/flashes) and directly informs front-line referral/triage decisions.
Validity, Bias Control & Precision 6.0
Retrospective EHR-based cohort with potential misclassification and unmeasured confounding; sample size is reasonable (n=1,181) but several estimates have wide confidence intervals.
Patient-Oriented Outcomes 8.0
Outcome is retinal detachment, a clearly patient-important event with major morbidity relevance, not merely a surrogate marker.
Magnitude of Net Benefit 6.0
Provides clinically meaningful risk estimates (e.g., RD absolute risk 6.1% with floaters alone; higher with acute/many floaters), but net benefit is indirect (risk stratification) and potential downstream harms/burden of increased referral are not reported.
Implementability & Practicality 9.0
Assessment of symptom onset and floater burden is feasible in routine primary care without special equipment; can be incorporated into history-taking immediately.
Practice-Changing Potential 7.0
Suggests floaters (especially acute/many) may warrant at least as much urgency as flashes, which could alter counseling and referral thresholds, though observational design limits definitiveness.
2. 6.1
Social Risk-Informed Decision Support and Blood Pressure Control in a Primary Care Cluster Randomized Controlled Trial.
Overall: A pragmatic cluster RCT in primary care suggests EHR-based social risk decision support may improve blood pressure control, but the abstract omits key quantitative results, precision, and patient-important outcomes, limiting confidence in the size and real-world impact of benefit.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 9.0
Conducted in a large primary care network with workflows aimed at hypertension/diabetes management and social risk screening—highly aligned with common generalist decisions.
Validity, Bias Control & Precision 6.5
Pragmatic cluster randomized design supports causal inference, but the abstract provides no patient/sample sizes, baseline balance, effect estimates, confidence intervals, or attrition, limiting confidence and precision.
Patient-Oriented Outcomes 4.0
Primary outcomes are blood pressure control and HbA1c control, which are intermediate/surrogate markers rather than direct patient outcomes (e.g., cardiovascular events, mortality, quality of life).
Magnitude of Net Benefit 5.0
Reports a statistically greater improvement in BP control in intervention clinics, but provides no absolute effect size, HbA1c results, harms, or workload/burden data to judge the net clinical impact.
Implementability & Practicality 7.5
EHR-integrated decision support and screening alerts are plausible to deploy in routine primary care, but feasibility may depend on local EHR build resources and the abstract does not describe staffing/time requirements.
Practice-Changing Potential 4.5
Suggests embedding social risk-informed decision support may improve BP control, but the lack of quantitative effect sizes and patient-oriented endpoints makes it harder to justify immediate broad practice change from the abstract alone.
3. 5.8
Consultations with locum doctors in UK general practice: longitudinal analysis of electronic health records.
Overall: Highly relevant, large UK primary-care EHR analysis that informs workforce planning, but it is observational, lacks patient health outcomes, and does not quantify benefits/harms of locum care—so its main value is descriptive and policy-informing rather than directly guiding clinical care.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 9.0
Directly studies UK general practice consultations over 12 years and addresses workforce staffing (locum vs permanent GPs), a core primary-care operational issue.
Validity, Bias Control & Precision 5.0
Large retrospective EHR cohort with multilevel modeling, but observational design limits causal inference and the abstract provides limited detail on confounding control, missing data, and model performance/uncertainty.
Patient-Oriented Outcomes 1.5
Outcomes are service-delivery metrics (proportion of consultations by locums, geographic trends) rather than patient health outcomes, safety, satisfaction, or continuity-related outcomes.
Magnitude of Net Benefit 2.0
Reports prevalence and variation (e.g., mean 14.9% of consultations in 2019) but does not measure benefits or harms to patients or practices, so net benefit cannot be determined.
Implementability & Practicality 7.0
Findings are straightforward to interpret for planners (locum use levels and regional trends), though translating them into actionable interventions is not specified and determinants were 'largely unexplained.'
Practice-Changing Potential 10.0
Provides UK-wide, longitudinal benchmarking that suggests locum use is higher than official statistics, which could materially affect workforce planning discussions, measurement approaches, and local staffing strategies.
4. 5.5
Effect of Initiating HPV Vaccination Before Age 11 on HPV Vaccination Completion.
Overall: This retrospective primary-care–relevant study suggests earlier HPV vaccine initiation may improve completion, but limited methodological detail, lack of precision metrics, and reliance on a process outcome constrain confidence and immediate practice change.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 9.0
HPV vaccination timing and series completion is a routine, high-impact primary care task in pediatrics/adolescent care, and the population (ages 9–17) maps directly to outpatient practice.
Validity, Bias Control & Precision 4.0
Retrospective analysis with unclear sampling (subset of 613 from 2,380), limited reporting of methods and bias control, and incomplete effect reporting (odds ratio given without confidence intervals or clear adjustment), limiting causal inference and precision.
Patient-Oriented Outcomes 3.0
The outcome is vaccine series completion, which is an important process measure but not a direct patient health outcome (e.g., HPV infection, precancer, cancer, adverse events).
Magnitude of Net Benefit 4.0
The abstract suggests earlier initiation is associated with higher completion, but provides limited quantitative results and does not report harms, burden, or downstream clinical outcome improvements, making net benefit uncertain from the abstract alone.
Implementability & Practicality 8.0
Starting HPV vaccination before age 11 is operationally feasible in routine primary care using existing vaccines and visit structures, though the referenced multi-component, culturally tailored program may require additional resources not described.
Practice-Changing Potential 5.0
Supports an earlier-start strategy that could influence clinic workflows and messaging, but the observational design and limited reporting reduce confidence that this alone should change practice without stronger comparative evidence.
5. 5.3
Effect of an Advanced Community Paramedic Program to Shorten or Prevent Hospitalizations: A Pragmatic, Point-of-Care, Randomized Clinical Trial.
Overall: This pragmatic multicenter RCT is directly relevant to outpatient acute-care alternatives, but it found no reduction in acute care use and provides limited quantitative detail, yielding modest evidence for changing practice beyond potential satisfaction improvements.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 8.0
Tests a home-based acute-care alternative (community paramedics) aimed at preventing/shortening hospitalization—highly relevant to outpatient/ED-to-home pathways and family medicine populations, including rural patients.
Validity, Bias Control & Precision 7.0
Multicenter pragmatic randomized controlled trial (n=240) supports internal validity, but the abstract provides limited statistical detail (no effect estimates beyond means/SDs and no CIs/p-values shown) and the sample size limits precision for several secondary outcomes.
Patient-Oriented Outcomes 6.0
Includes patient-important measures (days alive out of hospital/ED, death, quality of life, falls with injury, medication errors, satisfaction), though the primary endpoint is utilization-focused rather than a direct health outcome and results are sparsely reported.
Magnitude of Net Benefit 3.0
No improvement in the primary outcome (days alive out of hospital/ED were similar between groups), implying little to no net clinical benefit; satisfaction improved, but harms/burdens and other clinical outcomes are not clearly quantified in the abstract.
Implementability & Practicality 5.0
A mobile community paramedic model is potentially scalable but requires staffing, coordination, and system-level infrastructure that many practices/regions may not have readily available.
Practice-Changing Potential 3.0
Given the neutral primary outcome and limited reported benefit beyond satisfaction, the findings are unlikely to drive broad immediate changes in care pathways without better targeting or clearer outcome gains.
6. 4.7
Why aren't they used? Systematic review of barriers to implementation of clinical decision support systems for early cancer detection in primary care.
Overall: Highly relevant to primary care implementation of cancer CDSSs, but the abstract provides limited methodological detail and no patient-outcome or effect-size data, so its main contribution is practical insight rather than evidence of clinical benefit.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 9.0
Focuses directly on primary care use of cancer-related clinical decision support for screening and symptomatic assessment—topics and workflows that generalists commonly face.
Validity, Bias Control & Precision 4.0
Described as a systematic mixed-methods review using a theoretical framework, but the abstract provides little on search strategy, study quality appraisal, or strength/consistency of included evidence; results reporting appears incomplete.
Patient-Oriented Outcomes 1.0
Outcomes are implementation barriers/themes rather than patient health outcomes (e.g., morbidity, mortality, quality of life).
Magnitude of Net Benefit 2.0
No quantified clinical benefits or harms of CDSS use are reported; the abstract only addresses barriers and contextual factors, so net benefit cannot be established.
Implementability & Practicality 7.0
Directly targets real-world implementation issues (workflow integration, medicolegal concerns, stakeholder involvement), offering potentially actionable considerations for deploying CDSSs in practice.
Practice-Changing Potential 5.0
May influence how teams approach adoption (e.g., focusing on diagnostic context and workflow), but it does not provide evidence that using CDSSs improves patient outcomes or clear, quantified effects to drive immediate practice change.
7. 4.3
Early cancer diagnosis and community pharmacies: a systematic review.
Overall: This review is highly relevant to primary-care-adjacent early cancer detection in community pharmacies, but the abstract provides limited outcome data or effect estimates, leaving uncertainty about patient benefit, harms, and readiness to change practice.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 8.0
Focuses on early cancer detection pathways at the community pharmacy interface, which is closely linked to the typical first-contact, symptom-presentation role of primary care and could affect referral/signposting decisions.
Validity, Bias Control & Precision 5.0
A systematic review with dual screening is a strength, but the abstract provides little about risk-of-bias assessment, heterogeneity, or quantitative synthesis, and the results section is incomplete with no precision estimates.
Patient-Oriented Outcomes 3.0
The abstract does not clearly report patient-important endpoints (for example stage shift, time to diagnosis, morbidity, mortality, quality of life) and emphasizes the need to define relevant clinical outcomes.
Magnitude of Net Benefit 2.0
No effect sizes, harms, workload, or downstream consequences are reported, so the net benefit cannot be judged from the abstract.
Implementability & Practicality 5.0
Community pharmacies are inherently accessible and scalable, and barriers/facilitators are a stated aim, but specific operational details (training, pathways, information sharing, resources) and real-world performance are not provided.
Practice-Changing Potential 3.0
The conclusion highlights that robust large-scale trials are still needed, suggesting current evidence is insufficient to justify immediate changes in routine practice.
8. 4.2
Decision support tools for pancreatic cancer detection: external validation in Australian primary care - a retrospective cohort study.
Overall: Primary-care–relevant external validation study, but key quantitative results and precision details are missing, outcomes are largely predictive/diagnostic rather than patient-centered, and the reported lack of strong tool performance limits net benefit and immediate impact on practice.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 8.0
Directly evaluates pancreatic cancer risk-assessment/decision-support tools using Australian primary care encounter data, aligning with generalist diagnostic decision-making.
Validity, Bias Control & Precision 4.0
Retrospective cohort with linked registry data supports case ascertainment, but the abstract provides no sample size, no performance metrics (e.g., sensitivity/specificity/AUC), and limited methodological detail, making precision and bias control hard to judge.
Patient-Oriented Outcomes 2.0
Assesses diagnostic accuracy/prediction performance rather than downstream patient outcomes such as stage shift, treatment eligibility, morbidity, or survival.
Magnitude of Net Benefit 2.0
Concludes tools were not strongly predictive and provides no quantitative effect sizes or analysis of potential harms (false positives, investigations) versus benefits.
Implementability & Practicality 5.0
If accurate, such tools could be embedded in primary care systems, but the abstract does not describe workflow integration, required inputs beyond reason-for-encounter data, or resource implications; and performance appears inadequate.
Practice-Changing Potential 4.0
Useful as a cautionary external validation indicating existing tools may not transport well, but the lack of strong predictive performance and absence of actionable thresholds limits immediate practice change.
9. 4.2
A Retrospective Analysis of Soft Tissue Point-of-Care Ultrasound (POCUS) in Primary Care.
Overall: A primary-care–relevant descriptive study showing common non-abscess soft-tissue ultrasound findings and notable radiology wait times, but it lacks comparative design and patient-outcome data to support clear clinical benefit from POCUS.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 8.0
Addresses a very common primary-care presentation (soft tissue lumps/infection concerns) and a real-world decision point about imaging delays and referrals.
Validity, Bias Control & Precision 4.0
Retrospective, single-practice descriptive review with no comparator, limited generalizability, and potential selection/documentation bias; precision is limited despite reporting n=168 and basic descriptives.
Patient-Oriented Outcomes 1.0
Reports imaging findings, timing, and follow-up recommendations rather than patient-important outcomes (symptoms, function, complications, quality of life).
Magnitude of Net Benefit 2.0
Potential benefits of POCUS (faster diagnosis, fewer referrals) are suggested but not measured; no harms, false positives/negatives, downstream testing burden, or clinical impact estimates are provided.
Implementability & Practicality 6.0
POCUS can be integrated into outpatient primary care, but requires equipment, training, and quality assurance; the abstract does not detail workflow, costs, or training requirements.
Practice-Changing Potential 4.0
Provides useful needs-assessment data for curriculum expansion, but does not test a POCUS intervention or demonstrate improved clinical outcomes, so immediate practice change is limited.
10. 3.8
Evaluation of the Need for Comprehensive Care for Patients with Cystic Fibrosis.
Overall: A single-center retrospective EMR review suggests many adults with CF lack a documented PCP and may have lower vaccination rates, but it provides limited causal evidence and mostly process outcomes, so it is more hypothesis- and quality-improvement–generating than practice-changing.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 6.0
Directly addresses whether adults with cystic fibrosis have an identified primary care provider and receipt of preventive services, which intersects with primary-care responsibilities, but the population and setting are specialty-clinic based and not broadly generalizable to typical primary-care panels.
Validity, Bias Control & Precision 4.0
Retrospective, single-center EMR-based study with limited control of confounding and potential misclassification (PCP identified in EMR vs actually engaged); modest sample size and minimal reporting of precision beyond a few p-values.
Patient-Oriented Outcomes 3.0
Outcomes are largely care-process measures (PCP designation, vaccinations, screening completion) and a snapshot of uncontrolled blood pressure, without reporting downstream clinical events, quality of life changes, morbidity, or mortality.
Magnitude of Net Benefit 2.0
No tested intervention and no quantified absolute improvements attributable to any care model; findings are associative (lower vaccine rates without a PCP) and do not establish net benefit versus harms or burden.
Implementability & Practicality 5.0
The implied action (better integrating PCPs into CF care teams) is plausible but operational details, resources, and workflow requirements are not evaluated, making real-world implementation barriers unclear.
Practice-Changing Potential 3.0
Highlights a care gap and may prompt quality-improvement efforts, but the evidence is observational and does not demonstrate that changing care structures improves patient outcomes.
Score Guide: 9-10 Exceptional 7-8 Strong 5-6 Moderate 3-4 Weak 1-2 Poor
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