Cervical cancer is a major cause of cancer-related mortality, necessitating effective screening and diagnostic methods. This study aimed to assess the performance of cervicovaginal smear (CVS) and human papillomavirus (HPV)-DNA co-test. The pathology results of 225 female patients who underwent HPV-DNA testing with CVS between 2014 and 2022 and were subsequently diagnosed by colposcopic cervical biopsy or second CVS were retrospectively analyzed. CVS samples showed atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and cervical cancer. Concordance between the first and second diagnoses demonstrated moderate agreement for LSIL. ASCUS cases exhibited a significant correlation with HPV-DNA positivity and higher-grade cervical lesions. In biopsy, sensitivity and specificity for CIN1/LSIL were 87.5% and 53.3, respectively, while for CIN2-3/HSIL, they were 83.87% and 58.49%. HPV testing showed significant correlation with histopathologic results. In women over 40 years, more intraepithelial lesions were diagnosed compared to younger women (p < 0.005). The conventional smear technique proved reliable in detecting high-grade lesions. Despite the limitations of our study, our results emphasize the value of HPV-DNA testing to avoid unnecessary interventions and to establish appropriate follow-up strategies.