PROJECT SUMMARY/ABSTRACT In 2018, the World Health Organization (WHO) called for action towards achieving the global elimination of cervical cancer. A strategy for achieving this goal was ratified by member states in August 2020. The WHO plan calls for an aggressive approach of vaccination, screening, and treatment of the human papillomavirus (HPV), the single cause of cervical cancer. In low- and middle-income countries (LMIC), which bear 90% of the incidence and mortality of cervical cancer globally, it is estimated that these goals will not be reached until 2120 – a century from now. One way to markedly shorten this timeline is through HPV self-sampling and immediate treatment for those who screen positive. In order to scale-up HPV there must be a low-cost, effective test that is easy to use in the field. An optimal field test would allow women to collect their own samples without compromising efficacy. The only WHO prequalified test specifically developed for low resource settings is careHPV, which has relatively good sensitivity when a sample is taken by a clinician, but which performs poorly when self-sampled. There is an urgent need for evaluation of a low-cost self- sampling test that is effective and can be easily implemented in LMIC. AmpFire® (Atila Biosystems, CA), a new low-cost HPV test, has demonstrated high sensitivity in self-collected samples and may perform better than provider-collected careHPV. Furthermore, the current protocol for careHPV requires a 2-day visit because the machines are in a central location and require 3-4 hours for processing. AmpFire® can be run from local locations using a battery-operated PCR machine. Since these tests process in approximately 1 hour, a single- visit approach is feasible, which is more efficient for the health system and more convenient for patients. The purpose of this study is to compare the efficacy of AmpFire® versus careHPV for the detection of high grade precancer (cervical intraepithelial neoplasia, grade 2 or higher, or CIN2+) and to compare the efficacy and feasibility of each test through the following aims: Aim 1: To compare self-collected AmpFire® to standard provider-collected careHPV for the detection of high grade cervical precancer. Aim 2: Demonstrate that a single-visit approach using self-collected AmpFire® will result in lower loss to follow-up than the current conventional two-visit approach using provider-collected careHPV. Aim 3: Perform a cost- effectiveness analysis to compare efficacy, loss to follow-up and generalizability of self-sampled AmpFire® HPV versus provider-collected careHPV.