Cervical cancer (CC) remains a significant global health burden, ranking eighth in incidence and ninth in cancer-related mortality among women worldwide. Persistent infection with high-risk human papillomavirus (HPVhr) is the primary etiological factor in CC development. The SCCUT program in Romania was designed to enhance access to primary screening and assess HPVhr prevalence among women aged 25–65 years in the South-Muntenia region. Between August 2022 and November 2023, a total of 36,813 women were enrolled in the SCCUT program after providing informed consent. Based on age, participants underwent either a Pap test and/or HPVhr testing. Clinical and demographic data—including age, hormonal status, intrauterine device (IUD) use, presence of leucorrhea, and history of cervical interventions—were collected via structured questionnaires. HPVhr testing was performed using the AmpFire^® HPV Screening system and processed in the lead partner laboratory. Of the total cohort, 12.5% (n = 4,588) tested positive for HPVhr. HPVhr positivity was significantly associated with younger age (mean 45.12 ± 9.21 years vs. 46.28 ± 8.56 years; P < 0.001) and cyclic hormonal status (P < 0.001). No statistically significant associations were found between HPVhr status and IUD use, presence of leucorrhea, or prior cervical interventions (biopsies or cauterizations). The SCCUT program confirms the critical role of HPVhr in cervical carcinogenesis and supports its use as a first-line screening tool. These findings highlight the importance of implementing widespread primary HPVhr testing, particularly in underserved populations. Increasing public awareness, improving HPV vaccination rates, and expanding access to early detection programs remain essential for effective cervical cancer prevention in Romania and globally.