Allowing women to collect their own cervicovaginal lavage specimens for human papillomavirus (HPV) testing increased coverage and cervical abnormality detection rates in a community-based cervical cancer screening program, Dutch researchers said.
Among some 28,000 women who didn't show up for standard clinic-based screening, 26.6% of those offered a home specimen-collection kit followed through and were tested, compared with 16.4% of those receiving a series of letters asking them to go to a clinic for screening (P<0.001), reported Chris J.L.M. Meijer, MD, of VU University Medical Center in Amsterdam.
Even though the availability of home sample collection failed to persuade nearly three-quarters of reluctant women to undergo screening, the researchers declared the effort a success.
"It is feasible and effective to offer women who do not attend regular cervical screening programmes the choice of self-sampling by sending a device for collecting cervicovaginal specimens for high-risk HPV testing," they wrote online in BMJ.
They calculated that the self-sampling increased the percentage of women undergoing screening by five points, to 70% of eligible women in the areas involved.
In the Netherlands, all women 30 to 60 years old are requested to undergo cervical cancer screening once every five years. Dutch health authorities have been seeking ways to reach those who don't respond.
One possibility they wanted to evaluate in the current study, called PROHTECT, was that some women would be more amenable to screening if they could collect their own specimens for laboratory analysis, rather than have it done at a clinic.
A previous study found that home-collected samples could not be used for conventional cytology evaluation but were suitable for HPV molecular diagnostic tests, according to Meijer and colleagues.
In the current study, 28,073 women who were no-shows after receiving the standard screening invitations in 2005 were randomized in a 99:1 ratio to be offered either the home collection kit or another chance at clinic-based screening. The women were contacted from December 2006 to April 2007, with responses through December 2007 counted in the study.
The collection kit was a lavage device (Delphi Screener) that rinsed the upper vagina and cervix and retained the resulting fluid. Participants were instructed to mail it to a laboratory for testing with a hybrid capture II molecular diagnostic device that identified 13 different high-risk HPV subtypes.
Those with positive results on this test were told to contact their regular physicians for follow-up evaluation, which was to include both a repeat HPV screen and cytology testing.
Their disposition after that depended on the results of those tests. Those with negative repeat HPV screens and negative or absent cytology results could wait five years for their next screening. A positive result on the repeat HPV screen but negative or absent cytology findings led to a recommendation for follow-up screening in one year.
Those with abnormal cytology findings, irrespective of the results of the repeat HPV screen, were referred for colposcopy and biopsy as needed.
Women who said they had previously had a hysterectomy when they returned their specimens or reported for a clinic screening were excluded from the analysis.
Among 7,384 women who had not undergone hysterectomy and collected their own samples, 76 were eventually confirmed to have cervical intraepithelial neoplasias of grade III or higher, and another 23 had grade II lesions, Meijer and colleagues found.
The self-sampling group included 57% who had participated in the previous round of clinic-based screens, while 43% had not been screened then either. Compared with the first subgroup, these serial no-shows were at double the risk for clinically significant lesions (relative risk for grade II+ lesions 2.04, 95% CI 1.27 to 3.28; RR for grade III+ lesions 2.28, 95% CI 1.31 to 3.96), according to the researchers.
At each step of the screening process, some women and/or their physicians failed to follow the recommended procedures:
- Of the 757 women in the self-sampling group informed of positive HPV test results, 9.6% did not go to their physicians for confirmatory testing
- 36.1% of those reporting for follow-up testing did not have both cytology evaluation and repeat HPV testing
- Of the 182 women with abnormal cytology findings, 17.6% did not obtain colposcopy as advised
- Of participants with equivocal initial findings who were advised to undergo screening a year later, 42.8% did not do so
- 61.5% of those with abnormal HPV or cytology results at the one-year evaluation ignored recommendations for colposcopy
About 41% of the positive HPV test results with the self-collected specimens were not confirmed in the physician-collected samples. Meijer and colleagues suggested that the test's cutoff value for a positive result might have been set too low.
On the other hand, raising it enough to reduce the number of discrepant results substantially also reduced the sensitivity, such that six lesions of grade II or higher would have been missed, the researchers indicated.
Meijer and colleagues acknowledged that the compliance rates and accuracy of HPV testing with the self-collected specimens were less than optimal. But, pointing to the nearly 100 clinically significant lesions detected in the self-sampling group, they argued that this option should be offered more widely.
"Implementation is likely to pay off immediately in terms of protecting a subset of nonattendees known to be at increased risk of cervical cancer," they wrote.
The study was partly funded by Delphi Bioscience, which also provided the self-sampling kits, and by the screening organization Noord-Holland and Flevoland, and IKA (Comprehensive Cancer Center Amsterdam). Hybrid capture II kits and universal collection medium were provided by Qiagen.
Study authors reported relationships, primarily research funding, from Delphi Bioscience and Qiagen.
- Reviewed by Dori F. Zaleznik, MD Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner