Papilozumib Vaginal Gel for Exocervical Mucosal Restoration in Women With Human Papillomavirus (HPV)

Exocervical mucosal restoration score at Day 30

Exocervical mucosal restoration will be assessed by colposcopy in participants assigned to Papilozumib® vaginal gel alone. The investigator will score the exocervical mucosa using a 5-point scale: 1, severe ectopia with bleeding; 2, severe or extensive ectopia involving more than 50% from the external cervical opening; 3, moderate ectopia involving 25% to 50%; 4, mild ectopia involving less than 25%; and 5, no ectopia. Higher scores indicate greater exocervical mucosal restoration.

Participants with concordant cytology and colposcopy at Day 30

In participants assigned to Papilozumib® vaginal gel alone, the investigator will record whether the cervical cytology result is concordant with the colposcopic finding using a "Yes" or "No" response. The outcome will be reported as the percentage of participants with concordant findings.

Exocervical mucosal restoration score at follow-up visits

Exocervical mucosal restoration will be assessed by colposcopy using the 5-point scale: 1, severe ectopia with bleeding; 2, severe or extensive ectopia involving more than 50%; 3, moderate ectopia involving 25% to 50%; 4, mild ectopia involving less than 25%; and 5, no ectopia. Higher scores indicate greater mucosal restoration. The Day 30 assessment applies to the vaginal gel plus oral supplement arm and the usual clinical practice arm. Month 3 and Month 6 assessments apply to all study arms.

Percentage of participants with concordant cytology and colposcopy findings

The investigator will record whether the cervical cytology result is concordant with the colposcopic finding using a Yes or No response. The outcome will be reported as the percentage of participants with concordant findings. The Day 30 assessment applies to Arms B and C, and the Month 3 and Month 6 assessments apply to all arms.

Percentage of participants with normalization of abnormal cervical cytology

Among participants with abnormal cervical cytology at baseline, normalization is defined as a change from atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), or atypical glandular cells (AGC) to normal cervical cytology, with a concordant colposcopic finding. The reported outcome will be the percentage of participants meeting this combined definition of cytological normalization; colposcopic concordance will not be reported as a separate measurement within this outcome.

Percentage of participants with complete Human Papillomavirus Virus clearance

Complete human papillomavirus clearance will be assessed using genotyped polymerase chain reaction (PCR) testing. Complete clearance is defined as a negative HPV test or disappearance of all HPV genotypes detected at baseline. The reported value will be the percentage of participants meeting the definition of complete HPV clearance.

Vaginal microbiota community state type

Vaginal microbiota will be assessed by shotgun metagenomic sequencing and classified according to Community State Type (CST). Categories are: CST I, dominated by Lactobacillus crispatus; CST II, dominated by Lactobacillus gasseri; CST III, dominated by Lactobacillus iners; CST IV, characterized by low Lactobacillus abundance and the presence of anaerobic and facultative anaerobic microorganisms; and CST V, dominated by Lactobacillus jensenii. The distribution of participants across CST categories will be reported at each assessment.

Intestinal microbiota Shannon diversity index

Intestinal microbiota will be assessed in stool samples using shotgun metagenomic sequencing. Microbial diversity will be summarized using the Shannon diversity index. The Shannon diversity index will be reported at each assessment, with higher values indicating greater microbial diversity.