Effect of screening with primary cervical HPV testing vs cytology testing on high-grade cervical intraepithelial neoplasia at 48 months: the HPV FOCAL randomized clinical trial (vol 320, pg 43, 2018)

IMPORTANCE There is limited information about the relative effectiveness of cervical cancer screening with primary human papillomavirus (HPV) testing alone compared with cytology in North American populations. OBJECTIVE 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). DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial conducted in an organized Cervical Cancer Screening Programin Canada. Participantswere recruited through 224 collaborating clinicians from January 2008toMay 2012, with follow-up through December 2016. Women aged 25 to 65 years with no history of CIN2+ in the past 5 years, no history of invasive cervical cancer, or no history of hysterectomy;whohave not received a Papanicolaou test within the past 12 months; andwhowere not receiving immunosuppressive therapywere eligible. INTERVENTIONS A total of 19 009 women were randomized to the intervention (n = 9552) and control (n = 9457) groups.Women in the intervention group received HPV testing; those whose results were negative returned at 48 months.Women in the control group received liquid-based cytology (LBC) testing; those whose results were negative returned at 24 months for LBC.Women in the control group who were negative at 24 months returned at 48 months. At 48-month exit, both groups received HPV and LBC co-testing. MAINOUTCOMESANDMEASURES Theprimaryoutcomewasthecumulativeincidence ofCIN3+48 months following randomization. The cumulative incidence of CIN2+was a secondary outcome. RESULTS Among 19 009 women who were randomized (mean age, 45 years [10th-90th percentile, 30-59]), 16 374 (8296 [86.9%] in the intervention group and 8078 [85.4%] in the control group) completed the study. At 48 months, significantly fewer CIN3+ and CIN2+ were detected in the intervention vs control group. All Participants Baseline Negative Screen Incidence Rate/1000 (95% CI) at 48 mo Risk Ratio (95% CI) Incidence Rate/1000 (95% CI) at 48 mo Risk Ratio Intervention Group Control Group (95% CI) CIN3+ 2.3 (1.5-3.5) 5.5 (4.2-7.2) 0.42 (0.25-0.69) 1.4 (0.8-2.4) 0.25 (0.13-0.48) CIN2+ 5.0 (3.8-6.7) 10.6 (8.7-12.9) 0.47 (0.34-0.67) CONCLUSIONS AND RELEVANCE Among women undergoing cervical cancer screening, the use of primary HPV testing compared with cytology testing resulted in a significantly lower likelihood of CIN3+ at 48 months. Further research is needed to understand long-term clinical outcomes as well as cost-effectiveness. © 2018 American Medical Association. All rights reserved.