Purpose: Human papillomavirus is suggested as a well-known risk factor for cervical cancers and nowadays, primary HPV typing is recommended as an alternative test to cervical cytology. Methods: This cross-sectional study evaluated the liquid-based cervical smears of 700 women with no history of HPV vaccination and cervical dysplastic disease from 2017 to 2020 in Isfahan, Iran. Here, we try to compare the prevalence of HPV genotypes using COBAS (@roch) with the results of pap smear cytology in evaluating the most appropriate test for cervical cancer screening, especially in low-resource societies. Results: The prevalence of HPV infection was 23.3%, including 8.7% with HPV 16/18 and 14.6% with other HR (high-risk) HPVs. Considering positive HPV genotypes, the frequency of HR HPV decreases in older age groups; 42.1% compared to 6.8%. In cytology reports, 8 out of 16 individuals with high-risk lesions were negative for any type of HPV; on the other hand, there were 129 HR HPV-positive patients out of 570 negative or low-risk pap smear results.Conclusion: It assumed that there is no superiority for HPV genotyping over cytology or vice versa in detecting high-risk patients for cervical cancer; As only 26.8% of women with HPV show abnormal cytology; and from those with normal cytology, 17.9% were positive for HR HPV. Screening with one method had a rare but high risk of delay in the timely detection of cervical cancer. Above that, the high prevalence of HPV infection in unvaccinated women also reveals the need for studies on the cost-effectiveness of universal vaccination.