HPV testing compared with cytology may result in less cervical intraepithelial neoplasia

Clinicians will have to choose between primary human papillomavirus testing and co-testing based on modeling and cost-effectiveness studies, an editorial noted.


Human papillomavirus (HPV) testing compared with liquid-based cytology testing resulted in a significantly lower likelihood of cervical intraepithelial neoplasia (CIN) of grade 3 or worse at 48 months, a study found.

To evaluate the two tests, researchers conducted a randomized clinical trial in an organized cervical cancer screening program in Canada. From January 2008 to May 2012, participants were recruited through 224 collaborating clinicians; follow-up continued through December 2016. Eligible women were ages 25 to 65 years; had no history of CIN2+ in the past five years, no history of invasive cervical cancer, or no history of hysterectomy; had not received a Pap smear within the past 12 months; and were not receiving immunosuppressive therapy.

There were 19,009 women randomized to the intervention (n=9,552) and control (n=9,457) groups. Women in the intervention group received HPV testing and returned at 48 months if their results were negative. Women in the control group received liquid-based cytology testing and returned at 24 months for retesting if their results were negative, then returned again at 48 months if results at 24 months were negative. At 48 months, both the intervention and control groups received HPV and liquid-based cytology co-testing.

The study's primary outcome was the cumulative incidence of CIN3+ 48 months after randomization, with cumulative incidence of CIN2+ as a secondary outcome. Results were published by JAMA on July 3.

At 48 months, significantly fewer cases of CIN3+ and CIN2+ were detected in the intervention group compared to controls. The incidence rate for CIN3+ was 2.3/1,000 (95% CI, 1.5 to 3.5) in the intervention group and 5.5/1,000 (95% CI, 4.2 to 7.2) in the control group. The risk ratio for CIN3+ was 0.42 (95% CI, 0.25 to 0.69). The incidence rate at 48 months for CIN2+ was 5.0/1,000 (95% CI, 3.8 to 6.7) in the intervention group and 10.6/1,000 (95% CI, 8.7 to 12.9) in the control group, and the risk ratio for CIN2+ was 0.47 (95% CI, 0.34 to 0.67). Women who were negative for HPV at baseline had a significantly lower cumulative incidence of CIN3+ at 48 months compared to cytology-negative women (CIN3+ incidence rate, 1.4/1,000 [95% CI, 0.8 to 2.4]; CIN3+ risk ratio, 0.25 [95% CI, 0.13 to 0.48]).

An editorial stated that the declining prevalence of HPV disease following HPV vaccination will make the marginally better sensitivity of co-testing irrelevant.

“Until that occurs, clinicians will have to choose between primary HPV testing and co-testing based on modeling and cost-effectiveness studies, against the backdrop of intensive marketing by test manufacturers,” the editorialist wrote. “Amid this substantial shift, new screening tools must be combined with redoubled efforts to engage inadequately screened women in order to make further progress against cervical cancer.”