IntroductionHaving good knowledge and a favorable attitude toward human papillomavirus (HPV) and HPV vaccinations is the cornerstone for increasing the use of HPV vaccinations and preventing cervical cancer. The objective of this study was to evaluate the level of knowledge, attitudes, and practices regarding HPV and HPV vaccinations, as well as to identify associated factors among female undergraduate health science students at both the University of Gondar (UoG) and Bahir Dar University (BDU), Amhara, Ethiopia.MethodsInstitutional-based multicenter descriptive cross-sectional study was conducted from June 1, 2023, to July 30, 2023. A multistage sampling technique was used to select 633 female undergraduate health science students, and data were collected using a structured, self-administered questionnaire. The data were coded, entered in Epi-data, and exported to SPSS for analysis. Variables with a P-value < 0.25 in the bivariate analysis were inserted in a multivariate logistic regression model, and those with a P-value of < 0.05 in the multivariate binary logistic regression were considered statistically significant factors for knowledge, attitude, and practice regarding HPV and vaccine against it.ResultsThe study included 600 participants with a mean age of 20.8 ± 0.75 years. Using Bloom’s cutoff points for the KAP study, among the participants, 436 (72.7%) had good knowledge about HPV, whereas 315 (52.5%) had good knowledge about HPV vaccinations. More than half of the participants, 359 (59.8%) heard about HPV vaccinations in Ethiopia. More than half of the participants, 342 (57%) had favorable attitudes toward HPV vaccinations. Only 261 (43.5%) participants believed the HPV vaccine was safe and effective. All participants had never been tested for HPV, and 471 (78.5%) refused to have their samples for regular HPV testing. The factors like ages between 21 and 23 years (AOR, 2.12, 95% CI: 1.22–3.09) and favorable attitudes toward HPV vaccinations (AOR: 1.88; 95%, CI: 1.15–3.41) were associated with the participant’s knowledge about HPV vaccinations. Having good knowledge about the virus (AOR: 1.92; 95%, CI: 1.11–5.88) and its vaccine (AOR:1.60; 95%CI: 1.07–2.47) were factors associated with the attitude of the participants about HPV vaccinations. Additionally, HPV vaccination practice was significantly associated with the attitude of the participants toward HPV vaccinations (AOR: 1.85; 95%CI: 1.15–3.45), knowledge about HPV (AOR: 1.18; 95%CI: 0.55–5.50), and HPV vaccinations (AOR: 1.85; 95%CI: 1.08–2.44).ConclusionThis study revealed that half of the students had good knowledge and a favorable attitude toward HPV vaccinations, but there was poor HPV vaccination practice. There is still a need for continued health education, training, and counseling services for students to strengthen HPV vaccination practices, improve students’ attitudes and knowledge about the benefits of vaccination, and improve counseling abilities against HPV-induced cancer.