Human Papillomavirus Infection, Cervical Intraepithelial Neoplasia (CIN), Low-Grade Squamous Intraepithelial Lesions
Conditions
Keywords
High-risk HPV, HPV Clearance, Human Papillomavirus, İmmunomodulator, Vaginal Ovule, Cervical Dysplasia, ASC-US, LSIL, CIN1, Randomized Controlled Trial
Brief summary
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.
Detailed description
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).
Interventions
DRUGOral Immunomodulator
Oral immunomodulator administered twice daily for 3 months.
DRUGVaginal Ovule
Vaginal ovule administered for 14 consecutive days each month for 3 months.
Standard supportive care according to routine clinical practice during the 3-month study period.
Sponsors
Dr. Lutfi Kirdar Kartal Training and Research Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Outcome assessors evaluating HPV test and cervical cytology results are blinded to treatment allocation.
Intervention model description
Participants are randomized in a 1:1 ratio to either dual-modality immunotherapy or standard supportive care and followed in parallel for three months.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Female patients aged 18-65 years. * Confirmed persistent high-risk human papillomavirus (HR-HPV) infection. * Histologically confirmed CIN 1 or cytological diagnosis of ASC-US or LSIL. * Eligible for conservative follow-up without immediate excisional treatment. * Ability to provide written informed consent and comply with study procedures.
Exclusion criteria
* HSIL, CIN2, CIN3, adenocarcinoma in situ, or invasive cervical cancer. * Pregnancy or breastfeeding. * Immunodeficiency or current immunosuppressive therapy. * Previous treatment for cervical dysplasia within the last 6 months. * Planned colposcopy, cervical biopsy, or LEEP during the 3-month study period. * Known hypersensitivity to any study intervention. * Participation in another interventional clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HPV clearance rate | 3 months | The proportion of participants with a negative high-risk HPV test at the end of the 3-month treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cytological regression | 3 months | Proportion of participants demonstrating regression of cervical cytology after treatment. |
Countries
Turkey (Türkiye)
Outcome results
None listed