This study aimed to determine the feasibility of vaginal/cervical nurse-assisted self-sampling (NASS) and the agreement between human papilloma virus (HPV) tests on self-samples versus clinician-taken (CT) specimens.Women participated voluntarily for cervical cancer screening at St. Aklesia Memorial Hospital. Eighty-three women provided a total of 166 coupled self-taken and CT specimens collected. Specimens were stored at room temperature for a maximum of 10 months and analyzed using validated the RIATOL qPCR HPV genotyping test, a quantitative polymerase chain reaction (qPCR) high-throughput HPV E6, E7 assay. The average age of the participating women was 32 years. Seventy-three women (87.9%) felt that NASS was easy to use. An overall HPV, high-risk (HR) HPV, and low-risk HPV prevalence was 22.7% (15/66), 18.2% (12/66), and 6.1% (4/66), respectively. The overall HR HPV prevalence was 17.2% (NASS) and 15.5% (CT). The most prevalent HPV type was HPV51; HPV 16 was only detected in 1 woman (CT+NASS) and HPV18 only in 1 woman (CT). The overall measurement agreement between self-taken and CT samples was moderate with a kappa value of 0.576 (P < .001). Lifetime partnered with >2 men were associated with HR HPV positivity (P < .001). There was a strong statistical association between HR HPV positivity and visual inspection with acetic acid- positive (P < .001). The NASS for HPV testing could be seen as an alternative option and might be acceptable to Ethiopian women. The overall HR HPV prevalence was comparable with Sub-Saharan countries in the general population.