Researchers at the University of Washington and four other health institutes explore whether at-home screening tests are an efficient and effective way to detect cervical precancer.
Every year, an estimated 12,000 women in the United States are diagnosed with HPV-associated cervical cancer, according to the CDC. Half of these diagnoses are in women who are underscreened.
“Pap screening is very effective for reducing cervical cancer incidence and mortality, yet one in four U.S. women are either overdue for routine screening or have never been screened,” says Rachel Winer, PhD, Professor of Epidemiology with the UW Department of Epidemiology and Affiliate Investigator at Kaiser Permanente Washington Health Research Institute. “These underscreened women are a high-priority population to get screened.”
To determine whether mailed HPV self-sampling kits, similar to those used to detect colorectal cancer, would help improve early detection and treatment of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and increase the uptake of cervical cancer screening, Dr. Winer and her colleagues launched their study, “Effect of Mailed Human Papillomavirus Test Kits vs. Usual Care Reminders on Cervical Cancer Screening Uptake, Precancer Detection, and Treatment: A Randomized Clinical Trial.”
“Home-based HPV screening can address several barriers to clinic-based screening, including those related to logistics, such as difficulty scheduling, finding transportation or childcare, or taking time off of work, [and] fear of pelvic examinations and prior negative experiences with screening,” Dr. Winer says. “Many studies have shown that an HPV test on a sample that a woman collects for herself performs as well as an HPV test done on a physician-collected sample. And randomized trials in other countries have shown that offering home-based HPV testing increases screening participation.”
London, England-based Belinda Nedjai, PhD, Senior Research Fellow and Director of the Molecular Epidemiology Lab at Queen Mary University of London, is one of those international investigators. Together with her team of researchers, Dr. Nedjai developed a noninvasive at-home screening test that would identify cervical pre-cancer through the analysis of urine and vaginal samples. They found that the self-screening tool was popular with women who used the test as part of a study led by Dr. Nedjai, leading the researchers to believe that it was likely to encourage more women to participate in cervical cancer screening.
“To the best of our knowledge, this study is the largest to test a methylation classifier, called S5, in urine and self-collected cervical samples to detect pre-cancer lesions in women who have been referred for further investigation,” Dr. Nedjai says in a press release published by the National Cancer Research Institute in London. “We expect the self-sampling test to improve acceptance rates for cervical cancer screening, as well as reducing costs to health services and improving the performance of screening programmes.”
“Now that primary HPV screening is a guideline-approved screening strategy in the U.S., there is a real possibility for home-based HPV screening to become a widespread option for women.”
— Rachel Winer, PhD, Professor of Epidemiology with the University of Washington Department of Epidemiology and Affiliate Investigator at Kaiser Permanente Washington Health Research Institute
The Anatomy of a Study
For her clinical trial conducted from 2014 to 2016, Dr. Winer enrolled 19,851 women ages 30 to 64 who were not in compliance with guideline-recommended intervals for cervical cancer screening, meaning they had never been screened or were overdue for a screening. Specifically, the women in the trial had not been screened for more than 41 months. Guidelines recommend having a Pap test every three years or a Pap test and HPV test together every five years.
A control group was notified about screenings through annual reminders and outreach from primary care clinics. The intervention group received these communications and was also mailed an HPV self-sampling package.
The research team’s primary outcomes were detection of CIN2+ within six months of screening and treatment within six months of CIN2+ detection. A secondary outcome was screening uptake within six months of randomization.
Dr. Winer and her fellow researchers found that by mailing home-based HPV screening kits to women in the United States healthcare system who were underscreened, they could increase cervical cancer screening by 50% in comparison with sending standard reminder communications related to Pap screening. However, they did not notice a statistically significant change in the detection or treatment of cervical precancers.
“When we designed the trial, we thought that the increase in screening with mailed HPV kits would be even higher than we observed,” Dr. Winer says. “This is one reason why we think there was not a significant increase in detection of precancers in the intervention group versus the control group. Cervical precancers are not very common, so we would have needed a larger difference in screening between the two groups in order to see a statistically significant difference in the number of precancers detected.”
Another reason that the research team did not find a statistically significant increase in precancer detection between the different randomization groups is that only some of the women who had positive HPV kit results participated in the recommended follow-up testing. A number of these women may have had precancers that were not detected for this reason.
“Our trial deployed several strategies to encourage appropriate follow-up of abnormal results, yet there was still a gap in follow-up adherence,” Dr. Winer says. “Given the complex and dynamic nature of U.S. cervical cancer screening guidelines, healthcare systems may need to devote additional resources to support screening, diagnostic and treatment completion when implementing new strategies such as home-based HPV self-sampling.”