The objective of the trial was to evaluate histologically confirmed cumulative incident cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) detected up to and including 48 months by primary HPV testing alone (intervention) or liquid-based cytology (control).
The trial was conducted in an organized Cervical Cancer Screening Program in Canada. Participants were recruited through 224 collaborating clinicians from January 2008 to May 2012, with follow-up through December 2016.
A total of 19 009 women aged 25 to 65 years with no history of cervical abnormalities were included in the study. From the 9552 women that were randomized to the group for primary HPV-testing 8296 completed the study and from the 9457 women that were randomized to the group for LBC 8078 completed the study (JAMA. 2018;320(1):43-52. doi:10.1001/jama.2018.7464).
Most important finding was that for the HPV screening group significantly fewer CIN3+ were
Detected (2.3%) vs the LBC group (5.5%), resulting in a risk ratio of 0.42 (95% CI: 0.25-0.69).
In the editorial comment L. Stewart Massad (MD) made some important remarks that seamlessly fit in the strategy of Self-screen that was set out with the founding of the company: improve sensitivity of cervical cancer screening by using primary HPV testing including subtyping, perform triage with molecular assays that are non-subjective and suitable for high through put testing, and make assays suitable for self-sampling.
Lower prevalence of cervical precancer due to vaccination has changed the accuracy of screening tests in ways that are only now being appreciated but that will further favor adoption of primary HPV screening by lowering its false-positive rate.
More recent assays provide HPV genotyping that allows nuanced risk stratification, especially immediate referral to colposcopy for women who screen positive forHPV16 orHPV18. Triage for women who test positive for HPV was by cytology, which may not be the optimal triage test because other assays that do not depend on cytotechnologists’ vigilance are becoming available for this purpose. However, these advances should result in fewer false-positive results, further favoring HPV screening over cytology.
A more fundamental important limitation to primary HPV testing is that better screening will have only marginal effects on cervical cancer incidence as long as most cervical cancers continue to occur in women who have been inadequately screened or improperly managed after an abnormal screen. Self-collected HPV test samples may be more acceptable than clinician-performed cervical cytology testing, but the success of colposcopy follow-up for women who prefer self-screening has not been shown in large-scale demonstration projects. Enhanced funding to improve screening outreach for underserved women appears unlikely in the current political climate.