The Mexican Cervical Cancer Screening (MECCS) study took place in the State of Michoacán. Primary screening was by self-sampling for high-risk human papillomavirus (HR-HPV). The objectives were to increase the specificity of primary HPV screening by requiring 2 positive HPV tests 1 year apart in women whose secondary screen was negative according to an acetic acid-aided visual inspection (VIA). In addition, we postulated that the sensitivity of VIA would be sufficient to identify large preinvasive lesions and cancers unsuitable for cryotherapy if applied in a see-and-treat algorithm.A total of 8621 women (aged 30-50 years) were screened, and 14.3% were positive for HR-HPV. In phase 1, 11.9% of the HPV-positive women were VIA-positive and were referred for colposcopy with directed and random biopsies. If VIA-negative, women repeated the self-sample 1 year later to detect persistent HR-HPV (25.2% were positive). If persistently HR-HPV-positive in phase 2, patients again had VIA, then all women (both VIA-positive and -negative) received directed and random biopsies. If cryotherapy had been used to treat HPV- and VIA-positive women in phase 1 or persistent HR-HPV-positive (phase 2), the potential risk of undertreatment would have been 4.1%, and 66.4% of the treated patients would have had normal or cervical intraepithelial neoplasia I on biopsy. The VIA triage would refer 0.73% of the patients to colposcopy owing to the lesion size, location, or the presence of a cancer. On the basis of this pilot study, we are encouraged to explore and evaluate a rapid, more sensitive, and more specific self-test.