The Effectiveness of High Resolution Microendoscopy for People Living With HIV

Baylor College of Medicine

Status and phase: Completed; Phase 2; Phase 1

Conditions: Anal High Grade Squamous Intraepithelial Lesion

Treatments: Diagnostic Test: High resolution anoscopy; Drug: Proflavine Hemisulfate; Diagnostic Test: mHRME (Mobile High resolution microendoscope)

Study type: Interventional

Funder types: Other

Identifiers

NCT04563754

H-44616 Anal HRME

Details and patient eligibility

About

The investigators have developed a portable, battery-operated, mobile high-resolution microendoscope (mHRME) that provides subcellular images of the anal epithelium, delineating the cellular and morphologic changes associated with neoplasia. The investigators' central hypothesis is that this 'optical' approach will increase the efficiency, clinical impact, and cost-effectiveness of the current standard of high-resolution anoscopy(HRA)-guided biopsy, thus facilitating usage by less-experienced clinicians in community-based or low-resource settings. To validate this, the investigators will conduct a study to determine the efficiency and diagnostic characteristics of the mHRME 'optical biopsy' approach versus the current standard of HRA-based tissue biopsy. Successful results will allow for improved efficacy and resource utilization for cancer screening in people living with HIV for anal cancer and other epithelial cancers including the cervix, oral cavity, bladder, and GI tract.

Full description

The investigators' central hypothesis is that using mHRME plus three-dimensional (3D) mapping as a diagnostic tool will improve the accuracy and efficiency of HSIL diagnoses. Additionally, the investigators hypothesize that the sensitivity (SN) specificity (SP), positive predictive value (PPV), and negative predictive value (NPV), as well as the receiver operating characteristic (ROC) curve for the identification of neoplasia on a per biopsy and per patient basis will be high. The investigators will first compare the HRA-directed biopsy (as the gold standard) to the results of the mHRME HSIL diagnosis. The SN of mHRME diagnosis in the detection of HSIL will be estimated with the binomial proportion of study participants who are positive for HSIL on HRA-guided biopsy at two thresholds of histology thresholds which are: 1) Anal intraepithelial neoplasia (AIN) 2+ threshold, and 2) AIN3+ threshold. SP will be estimated as the proportion of study participants who are negative for HSIL on HRA-guided biopsy at both thresholds. PPV and NPV will be estimated using the binomial proportion and 95% confidence interval (CI). In addition, Cohen's kappa statistic and ROC curves will be generated if patient characteristics such as low Clusters of differentiation 4 (CD4) count, combined antiretroviral treatment (cART) utilization, or high HIV viral load impact the determination of SN and SP. SN and SP of mHRME-based HSIL diagnosis will be estimated on a per lesion and per patient basis with 95% CI and compared by McNemar's test. A generalized linear model for logistic regression with multiple correlated outcomes will compare SN and SP of each method on a per biopsy and per patient basis.

Primary Objective:

To determine if the mHRME plus 3D mapping improves the accuracy of anal HSIL diagnosis compared to the gold standard of histologic diagnosis of HSIL by HRA-guided biopsy.

Secondary Objectives:

Determination whether HRME changes the decision to perform biopsy.

Enrollment: 163 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Consentable patients with documented HIV disease
• Either: 1) previously documented HSIL or 2) abnormal anal cytology within the past 2 years
• Ages 18 years and older
• Seen at the Baylor-affiliated Thomas Street Clinic (TSC), Mount Sinai Hospital and affiliated clinics

Exclusion criteria

• Unable to undergo routine anoscopy
• Allergy or prior reaction to the fluorescent contrast agent Proflavine or Iodine
• Unable to give informed consent
• Current or prior history of Invasive Anal Cancer
• Known permanent or irreversible bleeding disorder, or other hematologic disorder that in the opinion of the investigator would place the patient at increased risk for adverse outcome from the procedure
• Pregnancy

Trial design

Primary purpose: Screening

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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163 participants in 1 patient group

mHRME

Experimental group

Description:

5-10 ml of proflavine hemisulfate (0.01%) will be applied on the anal epithelium. The mHRME will then be inserted and imaging of abnormal tissues will be performed. This is a single-arm study where all subjects will receive both standard of care HRA (High resolution anoscopy) and experimental mHRME imaging.

Treatment:

Diagnostic Test: mHRME (Mobile High resolution microendoscope)

Drug: Proflavine Hemisulfate

Diagnostic Test: High resolution anoscopy