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

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

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.

Study Overview

• Status: Completed
• Conditions: Cervical Cancer; Cervix Lesion
• Intervention / Treatment: Diagnostic test: digital PCR (dPCR) assay

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 145

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Tuvara Jenene King

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Women ≥ 18 years old who are presenting to UNC Gynecology clinics with or without dysplasia and may or may not need colposcopy, biopsy, or lesion excisions.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control; Negative high risk (HR)-HPV, cytology co-test	Diagnostic test: digital PCR (dPCR) assay; 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
CIN 1; Biopsy with low grade dysplasia	Diagnostic test: digital PCR (dPCR) assay; 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
CIN 2-3; Biopsy with high grade dysplasia	Diagnostic test: digital PCR (dPCR) assay; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Investigators: Principal Investigator: Shivani Sud, MD, University of North Carolina, Chapel Hill

Publications and helpful links

Helpful Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2020
• Primary Completion (Actual): June 26, 2024
• Study Completion (Actual): July 15, 2024

Study Registration Dates

• First Submitted: February 14, 2020
• First Submitted That Met QC Criteria: February 14, 2020
• First Posted (Actual): February 18, 2020

Study Record Updates

• Last Update Posted (Estimated): November 14, 2024
• Last Update Submitted That Met QC Criteria: November 13, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Precancerous Conditions; Uterine Cervical Diseases; Uterine Cervical Dysplasia
• Other Study ID Numbers: LCCC 1928