Optimizing Screening for Cervical Cancer Among Women Living With HIV in the Dominican Republic

Study Overview
=================
Brief Summary
-----------------
This study compares different screening approaches to detect abnormal cell growth on the cervix that could be an early sign of cervical cancer. The lesions are caused by an infection of human papillomavirus, also called HPV. Using new methods to detect HPV may help doctors find ways to improve cervical cancer screening for women living with human immunodeficiency virus (HIV) in the Dominican Republic and in other countries.

Detailed Description
-----------------
OUTLINE: Participants participate in three annual interviews and clinical exams that last approximately 2 hours. Study participants provide blood, urine, and swab samples from the cervix, anus, and vagina and receive a pelvic exam. Any positive results are followed up in the study clinic.

Official Title
-----------------
Estudio Oportunidad: Optimizing Screening for Cervical Cancer Among Women Living With HIV in the Dominican Republic

Conditions
-----------------
Malignant Female Reproductive System Neoplasm

Intervention / Treatment
-----------------
* Procedure: Biospecimen Collection
* Other: Interview


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women ages 25 - 49 years old will be eligible to participate in the study Women and transgender men living with HIV who have an intact cervix Intent to reside in the Santo Domingo area Ability to attend routine study visits at IDCP for at least 24 months during the study. If women report that they anticipate relocating in the subsequent 24 months or anticipate difficulty attending study visits they will not be eligible Ability to understand the study timeline and procedures and the willingness to complete the informed consent process are also inclusion criteria Exclusion Criteria: Women with a prior diagnosis of cervical cancer or a history of treatment for cervical precancerous lesions (CIN2+) will be excluded Women with significant physical, mental, or social conditions that would limit participation with study procedures will not be eligible for the study Women who are pregnant or report an intent to become pregnant in the subsequent 3 months will not be eligible for the study Women who have no history of vaginal sexual exposure will not be eligible for the study

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 49 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Screening (biospecimen collection, cytology, interview)<br>Participants participate in an interview and clinical exam, lasting approximately 2 hours. Participants undergo vaginal self-sampling, cervical provider-sampling, and collection of blood and urine samples. Participants also undergo a pelvic exam. After first interview and clinical exam at enrollment, participants have two subsequent study visits over a 2 year period. | Procedure: Biospecimen Collection<br>* Collection of blood; urine; cervical, anal, vaginal samples<br>* Other names: Biological Sample Collected;Other: Interview<br>* Attend interview<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of cervical precancerous lesions (CIN2+) by cytology vs HPV restricted genotyping | Compare performance characteristics of two screening strategies. Comparison between dichotomous tests will be summarized by: (i) the true positive rate (TPR) and (ii) the false positive rate (FPR). | At baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of cervical precancerous lesions (CIN3) by cytology vs HPV restricted genotyping | Compare performance characteristics of two screening strategies. Comparison between dichotomous tests will be summarized by: (i) the true positive rate (TPR) and (ii) the false positive rate (FPR). | At baseline | 
| Cross-sectional diagnostic accuracy of triage by dual staining among hrHPV positive WLWH to detect CIN2+ | Estimate the diagnostic accuracy parameters (TPR, FPR, positive predictive value or PPV, negative predictive value or NPV) and their approximate 95% confidence intervals for the p16/Ki-67 dual staining triage strategy for WLWH who tested positive for restricted hrHPV genotyping at Month 0. Will also assess and compare the accuracy parameters (TPR/FPR) of the dual staining method as it applies to hrHPV16 positive WLWH versus those who are positive for other types of hrHPV in two-sample (unpaired) comparisons of proportions (two-sample proportion tests). | At baseline | 
| Diagnostic accuracy of dual staining triage among hrHPV positive WLWH to detect CIN2+ by specimen collected and reading approach | Calculate (i) the Cohen's kappa and (ii) the concordance correlation coefficient to calculate agreement between the two methods. Use the McNemar test to compare the overall agreement between them. | At baseline | 
| Diagnostic accuracy of hrHPV genotyping to detect CIN2+ among WLWH by vaginal vs cervical sampling | Calculate (i) the Cohen's kappa and (ii) the concordance correlation coefficient to calculate agreement between the two methods. Use the McNemar test to compare the overall agreement between them. | At baseline | 
| CIN2+ Incidence | Estimate the cumulative incidence of newly detected CIN2+ over 2 years among women negative at previous time points. | At 12 and 24 months | 
| Detection of repeat CIN2+ | Calculate the proportion positive a second time for CIN2+ at Month 12 or 24. | At 12 and 24 months |