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HPV Testing More Effective Than Pap Test at Detecting Cervical Intraepithelial Neoplasia

JUL 10, 2018 | DANIELLE MROZ, MA
The results of a new study, published in JAMA, indicate that after 48 months, fewer cases of cervical intraepithelial neoplasia (CIN) grade 2 or 3 or worse (CIN2+, CIN3+) were found in women who were screened for cervical cancer with primary cervical human papillomavirus (HPV) testing versus women who were screened with cytology alone. These results suggest that HPV testing is able to detect CIN earlier and more accurately than cytology.

Although cervical cancer is one of the most preventable cancers in the United States through early detection and treatment of abnormal cervical cell growth prior to cancer development, about 12,000 women are diagnosed with cervical cancer in the United States each year. Two traditional screening tests—the Pap (cytology-based) and HPV tests—are used to detect cervical cell changes as well as HPV. Research has shown that about “99.7% of all cervical cancers are associated with a persistent cervical infection with an oncogenic HPV genotype preceding the invasive tumor.”

To this end, a team of investigators, led by Gina Suzanne Ogilvie, MD, DrPH, of the University of British Columbia Faculty of Medicine, in Vancouver, Canada, conducted a randomized clinical trial (HPV FOCAL) which included more than 19,000 women who were recruited between January 2008 and May 2012. Those women who fit the study criteria of being between the ages of 25 and 65 (mean age, 45 years), with no recent clinical history of CIN2+, or no history of invasive cervical cancer or hysterectomy, no recent PAP (within the past year) and who were not taking immunosuppressive therapy were included in the study.

Participants were randomized into either an intervention group (n = 9552) which received HPV testing, or a control group (n = 9457) which received liquid-based cytology (LBC) testing. Those patients in the HPV group who had negative results after the first round of testing returned for follow-up after 48 months, while patients tested with LBC who had 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.

The results of the study indicated that at 48 months, patients in the intervention group had significantly fewer incidence rates for CIN3+ (2.3/1000; 95% CI; 1.5-3.5) versus patients in the control group (5.5/1000; 95% CI; 4.2-7.2), with a risk ratio of 0.42 (95% CI; 0.25-0.69).

Patients in the intervention group reported similarly significant reduced rates of CIN2+ incidence (5.0/1000; 95% CI; 3.8-6.7) versus patients in the control group (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).

According to the investigators, participants 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). 

Based on these results, the investigators concluded that primary HPV testing is able to detect cervical neoplasia earlier and more accurately than cytology.

Previous research has shown that primary HPV testing alone, or in combination with cytology is associated with increased detection of precancerous lesions in the first round of screening; however, until this study there was a dearth of research on the results 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,” according to the study authors. “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.”

L. Stewart Massad, MD, of the department of Obstetrics and Gynecology at the Washington University School of Medicine in St. Louis, Missouri, wrote in an accompanying editorial on the study that “substantial patient education” stands in the way of HPV testing becoming the primary screening method over cytology and Pap testing. He went on to explain that women need to be educated about the importance of these tests for sexually transmitted diseases and how left untreated, HPV can progress toward cancer. Although the prevalence of HPV continues to decrease since the introduction of a vaccine, testing is still paramount to patient health and Dr. Massad believes that the introduction of new screening tools needs to be combined with efforts to educate and screen women in order to truly make progress in the fight against cervical cancer.  

A version of this article was originally published by MD Mag® as “HPV Testing Improves on Cervical Neoplasia Detection Versus Cytology Testing.”
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