Trial Information

Multicentric Study of Cervical Cancer Screening and Triage With Human Papillomavirus (HPV) Testing

The study will be conducted in several Latin American countries. Currently, the study has
started in one site in Colombia and soon another site in Mexico will start. In each
participating center, at least 5,000 women ages 30-64 years who are attending clinics for
cervical screening will be invited to participate in the study. Women who agree to
participate and sign the corresponding Institutional Review Board (IRB) approved consent
forms will undergo a pelvic examination, and cervical cells for primary screening and triage
will be collected. Recruitment specimens will be used for primary screening with an
established HPV DNA test (Food and Drug Administration FDA approved). All women who are
HPV-positive by the recruitment test, and a 2% sample of the HPV-negative women, will be
referred for a standardized colposcopy examination for diagnosis. At the colposcopy visit,
but before colposcopy is performed, a risk factor interview will be administered and
participants will undergo visual inspection of the cervix with acetic acid (VIA) and
collection of additional cervical cells and a blood specimen. The results of VIA will not be
disclosed to the colposcopist. During colposcopy, the colposcopists will obtain (2-4)
biopsies from any abnormally-appearing areas to ascertain neoplastic outcomes (CIN 3+) and
to direct treatment as required. All women who attend colposcopy will have a second round of
HPV testing approximately 18 months after recruitment and those who are HPV-positive will be
referred to colposcopy for final diagnosis. Data management and study supervision will be
the responsibility of the International Agency for Research on Cancer (IARC) and the local
Principal Investigators, most of whom are experienced HPV researchers.

The combined number of histologically-confirmed diagnoses of CIN 3+ (estimated n=500) will
be the outcome of primary interest for evaluation of the performance of the various triage
modalities. Our initial analyses will focus on comparisons of triage strategies that employ
a single method: VIA, conventional/liquid-based cytology, HPV DNA genotyping, HPV RNA
detection, detection of E6 proteins of high risk HPV types, or markers of HPV-induced
cell-cycle alterations (e.g., p16, ki67, etc). To the extent possible, molecular testing for
HPV triage will be carried out on the recruitment specimens to simulate a 'reflex testing'
approach wherein screening and triage are done on the same specimen without additional
visits. Subsequent analyses will consider various alternative strategies that employ more
than one triage methodology; e.g., HPV DNA genotyping followed by cytology. The
effectiveness and costs of each alternative strategy will be assessed under various
scenarios of feasibility, cost, and effectiveness.