Dual-Modality Immunotherapy for HPV Clearance (DUAL-HPV)

Overview

Persistent high-risk human papillomavirus infection is an important precursor of cervical cancer and related cervical lesions. This single-center, randomized, assessor-blinded, parallel-group controlled trial evaluates whether dual-modality immunotherapy consisting of an oral immunomodulator plus a vaginal ovule improves HPV clearance compared with standard supportive care. A total of 76 participants will be randomized in a 1:1 ratio. The primary outcome is HPV clearance confirmed by repeat HPV testing and cervical cytology after the 3-month treatment period. Treatment adherence and adverse events will also be monitored.

Persistent high-risk human papillomavirus infection is a major risk factor for cervical intraepithelial neoplasia and cervical cancer. Although many infections regress spontaneously, persistent infection may require close surveillance, and non-invasive therapeutic strategies that may enhance host immune response and promote viral clearance remain clinically relevant. This is a prospective, single-center, randomized, assessor-blinded, parallel-group controlled trial conducted at the Department of Gynecologic Oncology of Kartal Dr. Lutfi Kirdar City Hospital. A total of 76 participants will be randomized in a 1:1 ratio using a computer-generated allocation sequence, with 38 participants assigned to each group. Treatment allocation will be managed by an unblinded study team member. Outcome assessors will remain blinded to group assignment. Participants in the intervention arm will receive an oral immunomodulator twice daily together with a vaginal ovule administered for 14 consecutive days each month for 3 months. Participants in the control arm will receive standard supportive care. Eligible participants must have confirmed HPV positivity with low-grade cervical abnormalities, including ASC-US, LSIL, or CIN 1, and must not require an invasive cervical procedure such as biopsy, colposcopy-directed treatment, or LEEP during the 3-month study period. The primary endpoint is HPV clearance at the end of 3 months, confirmed by repeat HPV testing and cervical cytology. Participants will be monitored monthly for treatment adherence and adverse events. The planned sample size is 76 participants, with 38 participants per group, based on a two-sided alpha level of 0.05 and 80% statistical power. The study was approved by the Kartal Dr. Lutfi Kirdar City Hospital Scientific Research Ethics Committee (Approval No. 2026/010.99/26/46).