The aim of this study was to investigate the prevalence of peritoneal human papillomavirus (HPV) infection in different clinical cervical cancer (CC) settings, and its association with potential clinical and/or histological factors. This is a single-center, prospective, observational study. Consecutive patients with newly diagnosed or recurrent/persistent CC, between March 2019 and April 2020, were included. A group of patients undergoing surgery for benign gynecological conditions was included as control group. All patients underwent HPV-DNA test in the cervix and in the peritoneal cavity simultaneously at time of surgery. Two-hundred seventy-two patients had cervical and peritoneal HPV test analyzed. Cervical and peritoneal HPV positivity (PHP) was found in 235 (88.0%) and 78 (28.7%) patients, respectively; the prevalence of PHP was 17.7% in early stage, 28.8% in locally advanced cervical cancer (LACC) and 46.6% in the metastatic/persistent/recurrent setting (P =.001). No control patient was found to have peritoneal HPV infection. Higher frequency of PHP was documented in patients with larger tumor size (P =.003), presence of cervical HPV 16/18 genotypes (P <.001), higher number of cervical high-risk (HR)-HPV per patient (P =.018) and peritoneal carcinomatosis (P <.001). Multivariate analysis demonstrated that lack of preoperative cervical conization in early stages (P =.030), while higher International Federation of Gynecology and Obstetrics (FIGO) stage (P =.021) and presence of cervical HPV 16/18 (P =.001) in LACC, was associated with PHP. This is a proof-of-concept study. A number of potential clinical implications, including prognosis, could be obtained by further studies.