The Effectiveness of High Resolution Microendoscopy for People Living With HIV

Study Overview
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Brief Summary
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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 HRA (High resolution anoscopy)-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.

Detailed Description
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The investigators' central hypothesis is that using mHRME plus 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 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 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) AIN (Anal intraepithelial neoplasia) 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. Positive and negative predictive values will be estimated using the binomial proportion and its 95% confidence interval (CI). In addition, the Cohens kappa statistic, and receiver operator characteristic curves will be generated if patient characteristics such as low CD4 count, cART (combined antiretroviral treatment) 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 high resolution anoscopy (HRA)-guided biopsy Secondary Objectives Determination whether HRME changes the decision to perform biopsy

Official Title
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The Effectiveness of High Resolution Microendoscopy (HRME) in High Grade Intraepithelial Lesions (HSIL) Diagnosis for People Living With HIV

Conditions
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Anal High Grade Squamous Intraepithelial Lesion

Intervention / Treatment
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* Diagnostic Test: mHRME (Mobile High resolution microendoscope)
* Drug: Proflavine Hemisulfate
* Diagnostic Test: High resolution anoscopy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Interventional Model Description: This is a single-arm study where all subjects will receive both standard of care HRA (High resolution anoscopy) and experimental mHRME imaging.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mHRME<br>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. | Diagnostic Test: mHRME (Mobile High resolution microendoscope)<br>* SOC (standard of care) HRA with Lugol's iodine will be performed. Unstained (abnormal) area will be evaluated with mHRME for optical biopsy diagnosis: contrast agent will be applied to anal epithelium (5-10 ml of proflavine hemisulfate (0.01%)). The mHRME will then be inserted and imaging of abnormal tissues will be performed. This will add 2 to 6 minutes per procedure. This is a single-arm study where all subjects will receive both standard of care HRA (High resolution anoscopy) and experimental mHRME imaging.<br>Drug: Proflavine Hemisulfate<br>* Contrast agent will be applied to anal epithelium (5-10 ml of proflavine hemisulfate (0.01%)) to use with the mHRME<br>Diagnostic Test: High resolution anoscopy<br>* SOC (standard of care) HRA with Lugol's iodine will be performed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Performance characteristics: Sensitivity (SN), Specificity (SP), positive predictive value (PPV) and negative predictive values (NPV) | The primary outcome of this study is to measure the operating characteristics including SN, SP, PPV and NPV comparing the physician- and algorithm- guided HRME-based image compared to the Lugol's- guided physician diagnosis of HSIL during HRA | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Procedure efficiency | Diagnostic yield: The number of neoplastic biopsies/total number of biopsies obtained in patients who received biopsies. | Day 1 | 
| Procedure time | Change in total procedure time for HRA plus mHRME vs HRA guided biopsy | Day 1 |