ArticlesSelf-collection of vaginal specimens for human papillomavirus testing in cervical cancer prevention (MARCH): a community-based randomised controlled trial
Introduction
The public health burden of cervical cancer in developing countries is high.1 In 2008, about 37 000 deaths related to cervical cancer occurred in the Americas, costing about 545 000 DALYs.1, 2 Findings from randomised trials of more than 200 000 women3, 4, 5, 6, 7, 8, 9, 10 showed HPV DNA screening to be better than cervical cytology for detecting cervical intraepithelial neoplasia (CIN) grade 2 or worse, and for reducing incidence and mortality from cervical cancer. Furthermore, results of systematic reviews and meta-analyses11, 12, 13 showed that HPV testing has higher sensitivity but lower specificity than cytology. In recognition of the value of HPV DNA testing, focus has increased on assessment of HPV screening in different settings.14 The limited infrastructure of low-income countries reduces the effectiveness of cytology-based screening programmes. HPV testing of self-collected vaginal specimens could be especially useful for women with restricted access to health care15 and could increase population coverage16 because of increased acceptability and elimination of clinical examinations. Although good diagnostic performance and safety have been documented in research settings, no randomised trial has assessed the home-based performance of vaginal HPV testing.
With our Mexican Appraisal of Routine Cytology versus vaginal HPV screening (MARCH) trial—the first population-based randomised trial in a low-resource region—we aimed to assess the performance of HPV DNA testing on vaginal samples self-collected in the home versus routine cervical cytology. We postulated that HPV DNA testing of vaginal specimens would have similar or greater sensitivity and lower (but acceptable) positive predictive value than Papanicolaou (Pap) cytology in a comparison group of women.
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Patients
Our community-based randomised equivalence trial was commissioned, undertaken, and monitored between March, 2006, and April, 2007, by the Mexican Ministry of Health's evidence-based public health initiative. We began with a population-based list of 25 061 women aged from 25 to 65 years (figure). Participants came from 540 medically underserved, predominantly rural communities in Morelos, Guerrero, and the state of Mexico. Eligible women were participants in Oportunidades,17 a poverty-reduction
Results
Data are based on the per-protocol analysis unless otherwise noted. The figure shows study design and descriptive statistics. Of women randomised to the HPV group, 9202 of 9371 (98%) found at home participated, whereas 11 054 of 12 731 (87%) women randomised to cytology (including those not at home who were left a printed invitation) attended the local clinic for a Pap smear (p=0·001). The 2959 women in the HPV group who were not at home were reassigned to the cytology group (left a written
Discussion
In our study in underserved Mexican women, HPV testing was more sensitive for detecting invasive cervical cancer than was cytology, with a relative sensitivity of 4·2 (95% CI 1·9–9·2). Furthermore, HPV testing was 3·4 times more sensitive than cytology for detecting CIN 2 or worse, combined with a positive predictive value of 12·2%. Our findings support a possible change to front-line large-scale application of HPV testing in different settings in Mexico, particularly in areas with restricted
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These authors contributed equally