Elsevier

The Lancet

Volume 378, Issue 9806, 26 November–2 December 2011, Pages 1868-1873
The Lancet

Articles
Self-collection of vaginal specimens for human papillomavirus testing in cervical cancer prevention (MARCH): a community-based randomised controlled trial

https://doi.org/10.1016/S0140-6736(11)61522-5Get rights and content

Summary

Background

Vaginal self-sampling for human papillomavirus (HPV) DNA testing could increase rates of screening participation. In clinic-based settings, vaginal HPV testing is at least as sensitive as cytology for detecting cervical intraepithelial neoplasia (CIN) grade 2 or worse; however, effectiveness in home settings is unknown. We aimed to establish the relative sensitivity and positive predictive value for HPV screening of vaginal samples self-collected at home as compared with clinic-based cervical cytology.

Methods

We did a community-based, randomised equivalence trial in Mexican women of low socioeconomic status aged 25–65 years. Participants came from 540 medically underserved, predominantly rural communities in Morelos, Guerrero, and the state of Mexico. Our primary endpoint was CIN 2 or worse, detected by colposcopy. We used a computer-generated randomisation sequence to randomly allocate patients to HPV screening or cervical cytology. Eight community nurses who were masked to patient allocation received daily lists of the women's names and addresses, and did the assigned home visits. We referred women with positive results in either test to colposcopy. We did per-protocol and intention-to-screen analyses. This trial was registered with the Instituto Nacional de Salud Pública, Mexico, INSP number 590.

Findings

12 330 women were randomly allocated to HPV screening and 12 731 to cervical cytology; 9202 women in the HPV screening group adhered to the protocol, as did 11 054 in the cervical cytology group. HPV prevalence was 9·8% (95% CI 9·1–10·4) and abnormal cytology rate was 0·38% (0·23–0·45). HPV testing identified 117·4 women with CIN 2 or worse per 10 000 (95·2–139·5) compared with 34·4 women with CIN 2 or worse per 10 000 (23·4–45·3) identified by cytology; the relative sensitivity of HPV testing was 3·4 times greater (2·4–4·9). Similarly, HPV testing detected 4·2 times (1·9–9·2) more invasive cancers than did cytology (30·4 per 10 000 [19·1–41·7] vs 7·2 per 10 000 [2·2–12·3]). The positive predictive value of HPV testing for CIN 2 or worse was 12·2% (9·9–14·5) compared with 90·5% (61·7–100) for cytology.

Interpretation

Despite the much lower positive predictive value for HPV testing of self-collected vaginal specimens compared with cytology, such testing might be preferred for detecting CIN 2 or worse in low-resource settings where restricted infrastructure reduces the effectiveness of cytology screening programmes. Because women at these sites will be screened only a few times in their lives, the high sensitivity of a HPV screen is of paramount importance.

Funding

Instituto Nacional de Salud Pública, the Health Ministry of Mexico, QiAGEN Corp

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.

Section snippets

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

References (31)

  • Projections of mortality and burden of disease

  • MH Mayrand et al.

    Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer

    N Engl J Med

    (2007)
  • P Naucler et al.

    Human papillomavirus and Papanicolaou tests to screen for cervical cancer

    N Engl J Med

    (2007)
  • R Sankaranarayanan et al.

    HPV screening for cervical cancer in rural India

    N Engl J Med

    (2009)
  • A Anttila et al.

    Rate of cervical cancer, severe intraepithelial neoplasia, and adenocarcinoma in situ in primary HPV DNA screening with cytology triage: randomised study within an organised screening programme

    BMJ

    (2010)
  • Cited by (187)

    • Interprofessional Care in Obstetrics and Gynecology

      2022, Obstetrics and Gynecology Clinics of North America
    View all citing articles on Scopus

    These authors contributed equally

    View full text