Evidence Trace, complete trial record
In plain terms
In plain terms: HPV testing for cervical cancer screening has some human trial evidence supporting it, but the evidence is not yet strong enough for EBL to call it established. It is worth knowing about and worth discussing with your clinician.
HPV testing for cervical cancer screening
B
Supported: a good trial, backed by more
The endpoint this grade is based on: Hard clinical endpoint (mortality, major event)
The evidence as the record states it
Ronco et al. (Lancet, 2014; PMID 24192252): follow-up of four European randomized trials (Swedescreen, POBASCAM, ARTISTIC, NTCC), 176,464 women aged 20 to 64, HPV-based against cytology-based screening; invasive cervical cancer rate ratio 0.60 (0.40 to 0.89) over a median 6.5 years, with no heterogeneity between trials, and 0.45 (0.25 to 0.81) after the first 2.5 years; the trials' own primary endpoint was precancer. Sankaranarayanan et al. (N Engl J Med, 2009; PMID 19339719): 131,746 women aged 30 to 59 in 52 village clusters in India, one round of HPV testing, cytology or visual inspection against standard care; advanced cervical cancer hazard ratio 0.47 and cervical cancer deaths 34 against 64 (0.52, 0.33 to 0.83) with HPV testing; no significant reduction with cytology or visual inspection; mild adverse events in 0.1% of screened women. The trial reports: POBASCAM (Rijkaart et al., Lancet Oncol, 2012; PMID 22177579), NTCC (Ronco et al., Lancet Oncol, 2010; PMID 20089449) and Swedescreen (Naucler et al., N Engl J Med, 2007; PMID 17942872), each with precancer as its primary endpoint.
PMID 24192252 PMID 19339719 PMID 22177579 PMID 20089449 PMID 17942872
Evidence by specific use
Invasive cervical cancer, HPV-based against cytology-based screening, women aged 20 to 64
Grade B
Ronco et al. (Lancet, 2014; PMID 24192252) followed four randomized trials run by separate national groups: invasive cervical cancer was 40% less frequent with HPV-based screening (rate ratio 0.60, 0.40 to 0.89), with no heterogeneity between trials, and 55% less frequent after the first 2.5 years. The trials' own reports are POBASCAM (Rijkaart et al., Lancet Oncol, 2012; PMID 22177579), NTCC (Ronco et al., Lancet Oncol, 2010; PMID 20089449) and Swedescreen (Naucler et al., N Engl J Med, 2007; PMID 17942872). Replicated on a hard outcome, but as a follow-up rather than the trials' primary endpoint: B.
PMID 24192252 PMID 22177579 PMID 20089449 PMID 17942872
Cervical cancer deaths, one round of HPV testing against standard care, women aged 30 to 59 in rural India
Grade C
Sankaranarayanan et al. (N Engl J Med, 2009; PMID 19339719): 34 cervical cancer deaths with one round of HPV testing against 64 with standard care (hazard ratio 0.52, 0.33 to 0.83); one round of cytology or visual inspection did not significantly reduce deaths. One cluster trial, not repeated: C under Rule 06.
PMID 19339719
Why Grade B and not Grade A
Grade B reflects moderate human evidence -- typically a single strong trial, multiple smaller trials, or surrogate endpoint data without hard clinical outcome replication. To reach Grade A, HPV testing for cervical cancer screening would require at least one additional independent randomized trial demonstrating a hard clinical endpoint or objectively measured functional outcome in a comparable population.
What this grade covers and what it does not
Grade B on invasive cervical cancer with HPV-based against cytology-based screening: four independent European trials, pooled to 40% fewer invasive cancers (PMID 24192252). WHY NOT A: invasive cancer was a follow-up outcome, not the trials' primary endpoint, which was precancer. Grade C on cervical cancer deaths with one round of HPV testing against standard care: one cluster trial in India (PMID 19339719), not yet repeated (Rule 06). WHAT THIS GRADE DOES NOT COVER: the Pap test against no screening, which no repeated-round randomized trial has tested and which a single round did not clearly improve in India (PMID 19339719); HPV vaccination; and women under 25.
What would move this grade
An independent randomized trial demonstrating a hard clinical endpoint -- mortality, major adverse event, or objectively confirmed functional improvement -- in an adequately powered sample, with results independently replicated, would support Grade A.
How to track whether this is working
Measured in the trials: invasive cervical cancer diagnoses in registries, advanced cancer, and deaths from cervical cancer.