Effect of Papilozumib Oral on Vaginal and Intestinal Microbiota in HPV-Positive Women

Human papillomavirus infection has been associated with changes in the vaginal microbiota. The intestinal microbiota may also influence immune responses through the gut-vagina axis and could therefore be relevant to the persistence or clearance of HPV infection.

This was an exploratory, open-label, single-group interventional study in women aged 30 to 65 years with a positive HPV polymerase chain reaction test and either normal cervical cytology or cytological findings classified as atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), or atypical glandular cells (AGC).

Participants received Papilozumib, an oral synbiotic dietary supplement, for 3 months. The recommended daily dose was three capsules: two capsules in the morning while fasting and one capsule before the midday meal.

Vaginal and intestinal microbiota samples were collected at baseline and at Month 3. Microbiota composition was assessed using shotgun metagenomic sequencing to characterize the relative abundance and distribution of microbial taxa. Vaginal microbiota assessment included characterization of Lactobacillus-dominated community state types. Intestinal microbiota assessment included taxonomic composition and selected microbial functional genes.

Secondary assessments included HPV status by polymerase chain reaction, vaginal health measured using the Bachmann Vaginal Health Index, adverse events and tolerability, and adherence based on product-dispensing records. Safety evaluations included physical and gynecological examinations, vital signs, anthropometric measurements, and review of concomitant medications.

Inclusion criteria

• Female, aged 30 to 65 years, inclusive.
• Able to read and understand the Participant Information Sheet and Informed Consent Form.
• Willing to participate in the study and provide written informed consent.
• Normal cervical cytology or cytological findings of atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), or atypical glandular cells (AGC), confirmed no more than 3 months before the screening visit.
• Positive human papillomavirus (HPV) polymerase chain reaction test performed at the screening visit or available from no more than 3 months before the baseline visit.
• Able, in the investigator's judgment, to comply with the study requirements and follow the study instructions and assessments.

Exclusion criteria

• Clinically relevant immune system disorder, autoimmune disease, or current treatment with immunosuppressive agents.
• Systemic or local antibiotic, antifungal, or other treatment capable of altering the microbiota within 4 weeks before study treatment initiation.
• Undiagnosed abnormal genital bleeding within 6 months before the screening visit.
• Symptomatic vulvovaginal infection.
• Previous history of gynecological cancer.
• Current participation in another clinical trial or participation in another clinical trial within 4 weeks before study inclusion.
• Planned surgery that could prevent adherence to the study treatment regimen.
• Use of vaginal contraceptives or other vaginal hormonal treatments.
• Contraindication to the synbiotic dietary supplement or known allergy to any of its components.
• Woman of childbearing potential not using effective contraception, pregnancy, suspected pregnancy, or breastfeeding.