At 48 months, intervention patients significantly fewer incidence rates for CIN3+ versus control patients, with a risk ratio of 0.42.
Gina Suzanne Ogilvie, MD, DrPH
A new study has found that screening women with the primary cervical human papillomavirus (HPV) testing method is more likely to result in a lower likelihood of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) at 4 years.
A randomized clinical trial (HPV FOCAL) featuring 19,000-plus women at a cervical cancer screening program in Canada found that primary HPV testing is more than two-fold likely to reduce the rate of CIN3+ than cytology.
Led by Gina Suzanne Ogilvie, MD, DrPH, of the University of British Columbia Faculty of Medicine, in Vancouver, a team of 224 collaborating clinicians recruited female participants from January 2008 to May 2012 for exams, with follow-ups running through December 2016. Qualified women were aged 25-65 years old (mean age, 45 years), with no recent clinical history of CIN2+, or no history of invasive cervical cancer or hysterectomy.
Patients also had not received a Papnicolaou (Pap) test within the past year, and were not receiving immunosuppressive therapy at the time of recruitment.
Researchers randomized patients to either intervention (n= 9552) or control (n= 9457) groups, with intervention patients receiving HPV testing and control patients receiving liquid-based cytology (LBC) testing. HPV testing patients who had negative results returned for check-up in 48 months, while LBC testing patients with negative results returned at 24, then 48 months.
At the end of the 48-month checkup period, both groups received HPV and LBC co-testing.
At 48 months, intervention patients significantly fewer incidence rates for CIN3+ (2.3/1000; 95% CI; 1.5-3.5) versus control patients (5.5/1000; 95% CI; 4.2-7.2), with a risk ratio of 0.42 (95% CI; 0.25-0.69). Intervention patients reported similarly significant reduced rates of CIN2+ incidence (5.0/1000; 95% CI; 3.8-6.7) versus control patients (10.6/1000; 95% CI; 8.7-12.9) at 48 months. The CIN2+ risk ratio was 0.47 (95% CI; 0.34-0.67).
Women who were HPV-negative at baseline had a significantly lower cumulative CIN3+ incidence at 48 months than women who were cytology-negative, with a risk ratio of 0.25 (95% CI; 0.13-0.48).
The results, which indicate that primary HPV testing is a more early and accurate detector of cervical neoplasia than cytology, bucks trends surrounding such testing. Researchers noted that cytology-based cervical cancer screening is one of the most widely-used cancer control interventions in settings of high patient income.
Though previous findings have shown that primary lone HPV testing or in combination with cytology is associated increased detection of precancerous lesions in the first round of screening, various agencies have called for analysis of HPV testing beyond the initial phase.
“Previous studies found the benefit of HPV and cytology co-testing was based primarily on the contribution of HPV, which this trial now prospectively validates,” researchers wrote. “Further analyses modeling the cost-effectiveness of HPV primary screening using parameters from this study will be carried out to assess the potential economic effect of moving to HPV-based screening.”
In an essay accompanying the study, L. Stewart Massad, MD, of the Department of Obstetrics and Gynecology at the Washington University School of Medicine in St. Louis, wrote that “substantial patient education” stands in the way of HPV testing becoming the primary screening method over cytology and Pap testing.
“Women will need to understand the importance of testing for these sexually transmitted viruses, including that HPV infections are almost ubiquitous, may regress, and can be followed without therapy unless progressing toward cancer,” Massad wrote.
As HPV disease prevalence fades in the presence of a marketed vaccination, Massad noted the comparatively analyzing screening tests will soon become irrelevant. Until then, primary HPV testing and co-testing decisions should be based on such modeling and cost-effectiveness studies.
“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,” Massad wrote.
The study, "Effect of Screening With Primary Cervical HPV Testing vs Cytology Testing on High-grade Cervical Intraepithelial Neoplasia at 48 Months," was published online in JAMA last week.