Abstract
Persistent infection with high-risk human papillomavirus (hr-HPV) leads to cervical cancer (CC), the second most common cancer among women in Ethiopia. Understanding the genotype distribution of hr-HPV is essential for effective prevention strategies. However, existing studies in Ethiopia are fragmented and lack comprehensive national evidence. This study assessed the distribution of hr-HPV genotypes, cytological abnormalities, and their associated risk factors in women aged 30-65 in Ethiopia. A facility-based cross-sectional study was conducted from May 2024 to March 2025, including 735 women. Cervical samples were collected for cytological examination and multiplex PCR analysis, and all women were screened with visual inspection with acetic acid (VIA). Data were entered into EpiData version 4.7 and analyzed using SPSS version 27. Overall hr-HPV positivity was 16.2% (95% confidence interval: 13.6-19.2). HPV-16 was the most prevalent genotype (4.8% of all women and 29.4% of hr-HPV cases), followed by HPV-18 and HPV-35. VIA positivity rate was 13.3%. Abnormal cytology was found in 5.7% of women, of whom 40.5% had hr-HPV, while hr-HPV infection was present in 14.7% of women with normal cytology. Among hr-HPV cases, 65.6% of HPV types were not targeted by the current vaccine, and 30.9% of these non-targeted genotypes were detected in women with abnormal cytology. Having multiple sexual partners (aOR: 2.42), early sexual debut (aOR: 2.12), and a history of sexually transmitted infections (aOR: 1.81) were significantly associated with hr-HPV infection. High-risk HPV infection is high in the studied population in Ethiopia, with a significant proportion of genotypes not covered by the current vaccine. Adopting a nonavalent vaccine with sexual health education and regular screening is critical for comprehensive CC prevention.IMPORTANCEThe importance of this study lies in generating a comprehensive national evidence on high-risk human papillomavirus (hr-HPV) across multiple sites among Ethiopian women, addressing a significant gap in public health data. It documents the considerable burden of hr-HPV infection, identifies the most prevalent circulating genotypes, and reveals that a large proportion of infections are caused by genotypes not targeted by the currently used quadrivalent vaccine. This finding has profound implications for vaccine policy and cervical cancer (CC) prevention strategies in Ethiopia. By establishing clear associations between hr-HPV infection, cytological abnormalities, and behavioral risk factors, including multiple sexual partners, early sexual debut, and history of sexually transmitted infections. This study highlights the need for integrated prevention approaches. The evidence strongly supports the adoption of a broader-spectrum nonavalent vaccine, complemented with sexual health education and regular cervical screening programs, to effectively reduce the burden of hr-HPV and prevent cervical cancer in Ethiopian women.