Randomized, Double Blind Trial of the Quadrivalent HPV Vaccine to Improve Responses to LEEP Treatment of Cervical HSIL

Study Overview
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Brief Summary
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Cervical cancer occurs commonly in HIV-infected women in South Africa. These women have poor response to treatment of cervical cancer precursors. This study will test whether giving the quadrivalent vaccine to women prior to surgical treatment of the cervical cancer precursor will improve outcomes. We hypothesize that pre-treatment HPV vaccine will result in a reduced occurrence or cervical cancer precursors in follow-up.

Detailed Description
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This is a single-center, randomized, double-blinded, placebo-controlled, phase II trial of the quadrivalent human papillomavirus vaccine (qHPV) in HIV-infected women to prevent occurrence of cervical HSIL after LEEP/LLETZ. Participants will undergo colposcopy with directed biopsies, cervical cytology, and stored HPV testing prior to vaccination. Participants will be randomized to the quadrivalent vaccine or saline placebo to be given at entry, week 4, and week 26. Women will have LEEP treatment at week 4. Participants will be seen in follow-up for cervical cytology, colposcopy with directed biopsies at weeks 26 and 52, and stored HPV specimens. Treatment assignment will be unblinded after study follow-up is completed for the last study participant. Women aged 45 or less randomized to placebo will be offered open label HPV vaccine after the study is concluded..

Official Title
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A Randomized, Placebo-controlled Trial of Pre-treatment HPV Vaccination on Outcomes to LEEP Treatment of Cervical High Grade Squamous Intraepithelial Lesions in HIV-infected Women.

Conditions
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Cervical High Grade Squamous Intraepithelial Lesion

Intervention / Treatment
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* Biological: Human Papillomavirus vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV infection Women aged ≥ 18 years. Cervical HSIL on biopsy (i.e. CIN2 and/or CIN3) For participants of reproductive potential, negative serum or urine pregnancy test All study participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or in vitro fertilization) during study participation (from the time of study entry until week 52). Exclusion Criteria: History or current biopsy diagnosis of invasive or microinvasive cervical, vaginal, vulvar, anal or oropharyngeal cancer Prior hysterectomy Cervical cryotherapy or LEEP/LEETZ within one year of entry. Cervical, vulvar, or vaginal lesions suspicious for cancer, unless biopsies show no invasive cancer Prior receipt of one or more doses of an HPV vaccine. Receipt of anticoagulants other than aspirin or nonsteroidal anti-inflammatory drugs (NSAIDS) within 14 days prior to entry. Known allergy/sensitivity or any hypersensitivity to yeast or any of the components of the study product or its formulation (see section 5.2 for a list of components). Hemophilia or other bleeding diatheses. Use of any systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids, other than inhaled corticosteroids or prednisone ≤ 10 mg (or equivalent) , investigational vaccines, interleukins, interferons, growth factors, or intravenous immunoglobulin (IVIG) within 45 days prior to study entry. Breastfeeding Less than 3 months post-partum

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Human Papillomavirus vaccine<br>Participants receive the experimental quadrivalent Human Papillomavirus vaccine at entry, week 4 and week 26. | Biological: Human Papillomavirus vaccine<br>* The participants receive the qHPV vaccine at entry, week 4 and week 26<br>* Other names: qHPV vaccine;|
| Placebo Comparator: Saline placebo<br>The participants receive saline placebo at entry, week 4 and week 26. | Biological: Human Papillomavirus vaccine<br>* The participants receive the qHPV vaccine at entry, week 4 and week 26<br>* Other names: qHPV vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cervical HSIL | For this trial, the primary endpoint is high-grade squamous intraepithelial lesions (HSIL) or atypical squamous cells suggestive of HSIL found on cervical cytology, or HSIL found on cervical biopsy specimens at either the week 26 or week 52 visit. | up to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cervical Cytology | Cervical cytology abnormalities according to the Bethesda scale. The Bethesda scale classifies cytologic abnormalities. We have dichotomized the outcomes into high grade squamous intraepithelial lesions (HSIL)/atypical squamous cells suggestive of HSIL, or no evidence of intraepithelial lesions or malignancy (NILM)/atypical squamous cells of unknown significance (ASC-US)/low grade squamous intraepithelial lesions (LSIL). We report the number of women in each category. | Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, cervical dysplasia, LEEP, cervical cancer, HPV vaccination, gardasil, HSIL, CIN, HPV