Application of Plasma Circulating HPV DNA Testing to Management of Cervical Intraepithelial Neoplasia

Study Overview
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Brief Summary
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The purpose of this study is to see if circulating HPV DNA (cHPVDNA) can be used as a noninvasive biomarker for cervical intraepithelial neoplasia (CIN) 2-3 in hopes of reducing procedures and costs for patients, as well as personalize their treatment plan.

Detailed Description
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cHPVDNA is detectable in plasma of patients with invasive disease and CIN 1-3, and with the development of a highly sensitive and specific droplet digital Polymerase Chain Reaction (PCR) assay, it is hoped to be identified more prevalently and thus can improve risk stratification and help produce personalized treatment decisions and may be more cost-efficient. Plasma samples and cervical swabs will be collected from patients in University of North Carolina (UNC) Gynecology clinics, and some patients will also provide a urine sample. Those receiving biopsies or colposcopies and will come back to clinic 2-4 weeks post-excision for collection of another blood specimen. Using plasma samples and pathology results, we will characterize the relationship between plasma cHPVDNA levels and 1) CIN 1 versus CIN 2-3 pathology 2) CIN 2-3 pre-excision and 2-4 weeks post-excision. We will accrue three cohorts of 25, 30, 30 patients corresponding to 1) Control 2) CIN 1 3) CIN 2-3. The control cohort will establish background signal in the assay. We will compare the proportion of detectable cHPVDNA levels between CIN 1 and CIN 2-3 cohorts using Fisher's exact test with 80% power, significance level of 10%. Paired t-test will be used to compare pre- and post-excision cHPVDNA levels.

Official Title
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Application of Plasma Circulating Human Papillomavirus (HPV) DNA Testing to Management of Cervical Intraepithelial Neoplasia

Conditions
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Cervix Lesion, Cervical Cancer

Intervention / Treatment
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* Diagnostic Test: digital PCR (dPCR) assay


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: No history of previously treated cervical cancer Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee Exclusion Criteria: Women who are pregnant or nursing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control<br>Negative high risk (HR)-HPV, cytology co-test | Diagnostic Test: digital PCR (dPCR) assay<br>* It is a highly sensitive and specific droplet digital PCR assay for absolute quantification of circulating tumor HPV DNA for the most prevalent HPV types that will determine if a woman has cHPVDNA<br>|
| CIN 1<br>Biopsy with low grade dysplasia | Diagnostic Test: digital PCR (dPCR) assay<br>* It is a highly sensitive and specific droplet digital PCR assay for absolute quantification of circulating tumor HPV DNA for the most prevalent HPV types that will determine if a woman has cHPVDNA<br>|
| CIN 2-3<br>Biopsy with high grade dysplasia | Diagnostic Test: digital PCR (dPCR) assay<br>* It is a highly sensitive and specific droplet digital PCR assay for absolute quantification of circulating tumor HPV DNA for the most prevalent HPV types that will determine if a woman has cHPVDNA<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship between plasma cHPVDNA levels and presence of CIN 2-3 histopathology | We will quantify cHPVDNA levels in blood plasma from patients with normal screening, CIN 1, and CIN 2-3 cervical disease prior to treatment. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in cHPVDNA levels following excisional therapy for CIN 2-3 cervical disease. | For patients who undergo excisional therapy, we will collect bio-specimens and quantify cHPVDNA levels in plasma during their post-procedure visit. | 2-4 weeks post-excision |