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, women aged 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 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 (CIN3+) 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 CIN3+, including CIN2 lesions positive for p16, (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.