Screening Test Accuracy of a Gynocular™, HR-HPV Testing, and VIA for Detection of Cervical Intraepithelial Neoplasia, Grade Two and Above, in Women Living With HIV in Lusaka, Zambia

Screening Test Accuracy of Gynocular™, HR-HPV Testing, VIA for Detection of Cervical Neoplastic Lesions, in Women Living With HIV

Sponsors

Lead sponsor: University of Bern

Collaborator: Centre for Infectious Disease Research in Zambia
Cervical Cancer Prevention Program in Zambia
International Agency for Research on Cancer

Source University of Bern
Brief Summary

Cervical cancer in HIV-positive women is largely preventable through regular screening. The World Health Organization (WHO) recommends cervical screening for HIV-positive women every three years. Currently the least costly method for screening and the most viable option for many countries is visual inspection after application of acetic acid (VIA). Alternative testing methods are HPV testing and assessment with a portable magnification device. The investigators plan to assess and compare the screening test accuracy of these screening tests in women living with HIV. All women will receive histopathology reference standard.

Detailed Description

The simplest and least costly method for cervical cancer screening is visual inspection after application of acetic acid (VIA). However, the ability of this screening method to correctly identify precancerous lesions (sensitivity) and women free from these lesions (specificity) is limited. The investigators aim to identify alternative screening methods which maximize sensitivity and specificity, particularly in HIV-infected women in receiving care in Southern Africa. The investigators will evaluate the screening test accuracy of a new portable magnification device , the Gynocular™ with Swede score assessment, in women who are HIV-positive and eligible for cervical cancer screening. The investigators will assess the accuracy of the device when used as a stand alone test, as well as when used subsequent to positive VIA or HPV tests. The investigators will make comparisons with current screening practices (VIA alone), as well as, recommended screening practices (HPV testing). The investigators will enrol 450 HIV-positive women receiving care for HIV/AIDS at the Centre for Infectious Disease Research in Zambia, in Lusaka, Zambia. Consenting women will be screened with VIA, HPV testing and visual assessment with Gynocular™. All women undergo biopsy (reference standard) and receive treatment as indicated and in accordance with national guidelines.

Overall Status Recruiting
Start Date May 8, 2019
Completion Date December 1, 2022
Primary Completion Date January 1, 2021
Study Type Observational
Primary Outcome
Measure Time Frame
Test accuracy (sensitivity, specificity) of the Gynocular™ when used as stand-alone tests to detect CIN2+ 6 months
Test accuracy (sensitivity, specificity) of HR-HPV when used as stand-alone tests to detect CIN2+ 6 months
Test accuracy (sensitivity, specificity) of VIA when used as stand-alone tests to detect CIN2+ 6 months
Secondary Outcome
Measure Time Frame
Diagnostic test accuracy of the Gynocular™to detect CIN2+/HSIL: other estimates, stand alone 6 months
Diagnostic test accuracy of HR-HPV testing to detect CIN2+/HSIL: other estimates, stand alone 6 months
Diagnostic test accuracy of VIA to detect CIN2+/HSIL: other estimates, stand alone 6 months
Diagnostic test accuracy of HR-HPV testing followed by Gynocular™ to detect CIN2+/HSIL: test combination 6 months
Diagnostic test accuracy of HR-HPV testing followed by Gynocular™ to detect CIN2+/HSIL: test combination - subgroup analyses 6 months
Diagnostic test accuracy of the Gynocular™ followed by HR-HPV testing to detect CIN2+/HSIL: test combination 6 months
Diagnostic test accuracy of the Gynocular™ followed by HR-HPV testing to detect CIN2+/HSIL: test combination subgroup analyses 6 months
Diagnostic test accuracy VIA followed by Gynocular™ to detect CIN2+/HSIL: test combination 6 months
Diagnostic test accuracy VIA followed by Gynocular™ to detect CIN2+/HSIL: test combination - subgroup analyses 6 months
Diagnostic test accuracy of the Gynocular™ followed by VIA to detect CIN2+/HSIL: test combination 6 months
Diagnostic test accuracy of the Gynocular™ followed by VIA to detect CIN2+/HSIL: test combination - subgroup analyses 6 months
Diagnostic test accuracy of the HR-HPV followed by VIA to detect CIN2+/HSIL: test combination 6 months
Diagnostic test accuracy of the HR-HPV followed by VIA to detect CIN2+/HSIL: test combination - subgroup analyses 6 months
Diagnostic test accuracy of the VIA followed by HR-HPV to detect CIN2+/HSIL: test combination 6 months
Diagnostic test accuracy of the VIA followed by HR-HPV to detect CIN2+/HSIL: test combination subgroup analyses 6 months
Subgroup analyses for the diagnostic test accuracy of Gynocular™: stand alone test 6 months
Subgroup analyses for the diagnostic test accuracy of VIA: stand alone test 6 months
Subgroup analyses for the diagnostic test accuracy of HR-HPV testing: stand alone test 6 months
Subgroup analyses for the diagnostic test accuracy of VIA, HR-HPV testing and Gynocular™: Combined tests 6 months
Investigation of Swede Score in WLHIV 6 months
Investigation of co-infections of premalignant and malignant disease (STIs/HR-HPV) 6 months
Investigation of Trichomonas vaginalis prevalence and persistence in association with menstrual hygiene practices 6 months
Investigations to inform telemedicine capacity: Comparison of image quality 6 months
Investigations to inform telemedicine capacity: use of static images 6 months
Investigations to inform telemedicine capacity: ROC curve for Swede score 6 months
Investigations to inform telemedicine capacity: Live versus static assessors 6 months
Artificial Intelligence (AI) for improving the detection of precancerous cervical lesions: testing AI algorithm 6 months
Artificial Intelligence for improving the detection of precancerous cervical lesions: improve AI algorithm 6 months
Diagnostic test accuracy of AI tool to detect CIN2+/HSIL: other estimates, stand alone 6 months
Diagnostic test accuracy of HR-HPV testing followed by AI tool to detect CIN2+/HSIL: test combination 6 months
Enrollment 450
Condition
Intervention

Intervention type: Diagnostic Test

Intervention name: Screening for CIN2+/HSIL

Description: The investigators will compare three different screening methods: visual assessment with portable magnification device , visual inspection after application of acetic acid, screening for high risk variants of HPV. All patients will receive cervical biopsies and histopathological examination.

Eligibility

Sampling method: Non-Probability Sample

Criteria:

Inclusion Criteria:

1. HIV-infected women confirmed through medical records

2. Women residing within Lusaka district and plans to stay in this area for the next 6 months

3. Women between 18 and 65 years of age (age bracket as per Zambian guidelines for cervical cancer screening)

4. Able and willing to consent

5. Willing to undergo a pelvic examination and cancer screening

6. Has had sexual intercourse before

7. Agrees to have follow-up appointment in 6 months

Exclusion Criteria:

1. Women with a history of cervical cancer or previous hysterectomy (where the cervix was also removed)

2. Pregnant women or women who plan to get pregnant within the next 6 months

3. Women who have been vaccinated against HR-HPV

Gender: Female

Gender based: Yes

Gender description: Women

Minimum age: 18 Years

Maximum age: 65 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Julia Bohlius, MD Principal Investigator [email protected]
Overall Contact

Last name: Katayoun Taghavi, MD

Phone: +41 31 631 35 23

Email: [email protected]

Location
facility status contact Centre for Infectious Disease Research in Zambia Albert Manasyan, MD [email protected]
Location Countries

Zambia

Verification Date

May 2020

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Arm Group

Arm group label: Portable magnification device (Gynocular™)

Description: The Gynocular™ examination will be performed following the steps involved in colposcopy as described in the IARC colposcopy manual. These steps include: visualization of the vagina, vulva and cervix following insertion of a speculum, magnified assessment after application of normal saline, examination of cervical vessel patterns using the red-free mode (or green filter), application of 5% acetic acid for 1 minute and finally assessment following application with Lugol's iodine. The findings of the live examination will be documented using the parameters of the Swede score. Each parameter is scored between zero and two. Treatment will be based on the results found at histopathology, unless the woman is also VIA positive in which case, after biopsy she will undergo routine treatment as per local guidelines. The results will be used to determine the optimal threshold for treatment in WLHIV.

Arm group label: Testing for high risk HPV (HRHPV)

Description: To reduce the number of examinations undergone by the study participant during the same day, HRHPV testing will be carried out at the time of the first gynecological examination by the VIA nurse (see next arm). Using specific single-use cervical cytobrush provided by GeneXpert, a specimen will be collected immediately prior to VIA examination. Cervical cytobrush specimens will be placed into ThinPrep PreservCyt (Cepheid, Sunnyvale, CA) immediately after collection. The HR-HPV testing of cervical specimens will be conducted by a GeneXpert™ machine (Cepheid, Sunnyvale, CA), which will be placed at the health facility and will be operated by a trained nurse in accordance with the manufacturer's instructions. Additionally, as part of the baseline clinical characteristics of the study participant, the study participant will undergo an STI test at the same time. The sample will be collected and tested using the same GeneXpertTM platform.

Arm group label: Visual inspection with acetic acid (VIA)

Description: VIA, which is standard of care for cervical cancer screening in Zambia, will be carried out using the methodology described by IARC. This is summarized as follows: visualization of the vagina, vulva and cervix following insertion of a speculum; assessment with the naked eye after application of normal saline; and further assessment after application of 5% acetic acid for 1 minute. This will be recorded as normal or abnormal by the assessor.

Arm group label: Histopathological examination of tissue biopsies

Description: All acetowhite lesions will be biopsied. When no lesion is seen, one biopsy is taken from each quadrant at the squamocolumnar junction. Biopsies will be sent and examined in a South African based lab. All histological slides will also be verified independently by an IARC trained pathologist at the end of the study. Histological endpoints are defined by the CIN classification system: CIN 1 affects only the lower third of the epithelium (mild dysplasia), CIN 2 involves two thirds of the epithelium and CIN 3 involves the full thickness (severe dysplasia and carcinoma in situ). These findings can be dichotomized by the Lower Anogenital Squamous Terminology into low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL). All patients with CIN grade 2 that stained diffusely positive for p16 are considered as HSIL, all patients with CIN 3 are considered as HSIL. Expression of p16 will be visually assessed by immunohistochemistry.

Patient Data Undecided
Study Design Info

Observational model: Other

Time perspective: Prospective

Source: ClinicalTrials.gov