Randomized controlled trial of human papillomavirus testing versus Pap cytology for primary screening of cervical cancer precursors
Bibliographic record
Abstract
Introduction. Despite its successful history in cervical cancer screening, the false negative rate of Papanicolaou (Pap) cytology is an important concern. Testing for DNA of oncogenic human papillomaviruses (HPV) could circumvent this limitation. The present thesis reports the results of the first screening round of the Canadian Cervical Cancer Screening Trial (CCCaST). Objectives. To compare the performance (sensitivity, specificity, positive and negative predictive values) of HPV testing vs. Pap cytology in the detection of cervical cancers and their high-grade precursors and explore the impact of sampling order, test thresholds and combinations, and patient characteristics and laboratory on test performance. Methods. CCCaST is a randomized controlled trial (RCT) that compares HPV testing with Hybrid Capture 2 and conventional Pap cytology as screening interventions to identify high-grade cervical intraepithelial neoplasia among women aged 30-69 years in Montreal, Quebec, and St. John's, Newfoundland. Women with an abnormal Pap (≥atypical squamous cells) or a positive HPV (≥1 pg/ml of high-risk HPV DNA) underwent colposcopy and biopsy, as did a random sample of women with negative tests. Performance estimates were corrected for verification bias. Logistic regression modelling was used to investigate the importance of spectrum effect due to selected patient and laboratory characteristics. Results. 10,154 women were randomized. The sensitivity of HPV testing was substantially higher (94.6%, 95% confidence interval [CI]: 84.2-100) than that of Pap cytology (55.4%, 95%CI: 33.6-77.2), albeit with a slightly lower specificity (Pap: 96.8%, 95%CI: 96.3-97.3; HPV: (94.1%, 95%CI: 93.4-94.8). Performance was unaffected by which test was performed first. Use of both tests in parallel was 100% sensitive and 92.5% specific. Triage algorithms for Pap or HPV resulted in fewer referrals but were less sensitive. Spectrum effect analysis revealed that women over 40 reporting no new sexual partner in the last year would benefit from the higher sensitivity of HPV testing, while benefiting from comparable specificity to that of Pap cytology. Conclusion. The first RCT of HPV versus Pap testing for primary screening in North America demonstrates the greater sensitivity of HPV compared to cytology. Our study supports a paradigm change in cervical cancer screening.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.009 | 0.018 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.004 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.004 | 0.004 |
| Insufficient payload (model declined to judge) | 0.014 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".