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

NCT ID: NCT03931083

Last Updated: 2020-11-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

450 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-05-08

Study Completion Date

2022-12-01

Brief Summary

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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

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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.

Conditions

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Uterine Cervical Neoplasms HIV/AIDS

Study Design

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Observational Model Type

OTHER

Study Time Perspective

PROSPECTIVE

Study Groups

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Portable magnification device (Gynocular™)

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.

Screening for CIN2+/HSIL

Intervention Type DIAGNOSTIC_TEST

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.

Testing for high risk HPV (HRHPV)

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.

Screening for CIN2+/HSIL

Intervention Type DIAGNOSTIC_TEST

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.

Visual inspection with acetic acid (VIA)

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.

Screening for CIN2+/HSIL

Intervention Type DIAGNOSTIC_TEST

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.

Histopathological examination of tissue biopsies

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.

Screening for CIN2+/HSIL

Intervention Type DIAGNOSTIC_TEST

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.

Interventions

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Screening for CIN2+/HSIL

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.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Centre for Infectious Disease Research in Zambia

OTHER

Sponsor Role collaborator

Cervical Cancer Prevention Program in Zambia

UNKNOWN

Sponsor Role collaborator

International Agency for Research on Cancer

OTHER

Sponsor Role collaborator

University of Bern

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Julia Bohlius, MD

Role: PRINCIPAL_INVESTIGATOR

[email protected]

Locations

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Centre for Infectious Disease Research in Zambia

Lusaka, , Zambia

Site Status RECRUITING

Countries

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Zambia

Central Contacts

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Katayoun Taghavi, MD

Role: CONTACT

+41 31 631 35 23

Albert Manasyan, MD

Role: CONTACT

Facility Contacts

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Albert Manasyan, MD

Role: primary

References

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Taghavi K, Moono M, Mwanahamuntu M, Roumet M, Limacher A, Kapesa H, Madliwa T, Rutjes A, Basu P, Low N, Manasyan A, Bohlius J. Accuracy of screening tests for cervical precancer in women living with HIV in low-resource settings: a paired prospective study in Lusaka, Zambia. BMJ Oncol. 2024 Feb 10;3(1):e000111. doi: 10.1136/bmjonc-2023-000111. eCollection 2024.

Reference Type DERIVED
PMID: 39886160 (View on PubMed)

Taghavi K, Moono M, Mwanahamuntu M, Roumet M, Limacher A, Kapesa H, Madliwa T, Rutjes A, Basu P, Low N, Manasyan A, Bohlius J. Accuracy of screening tests for cervical pre-cancer in women living with HIV in low-resource settings: a paired prospective study in Lusaka, Zambia. medRxiv [Preprint]. 2023 Jun 1:2023.05.31.23290779. doi: 10.1101/2023.05.31.23290779.

Reference Type DERIVED
PMID: 37398043 (View on PubMed)

Taghavi K, Moono M, Mwanahamuntu M, Basu P, Limacher A, Tembo T, Kapesa H, Hamusonde K, Asangbeh S, Sznitman R, Low N, Manasyan A, Bohlius J. Screening test accuracy to improve detection of precancerous lesions of the cervix in women living with HIV: a study protocol. BMJ Open. 2020 Dec 18;10(12):e037955. doi: 10.1136/bmjopen-2020-037955.

Reference Type DERIVED
PMID: 33371015 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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KFS-4156-02-2017

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

Esther17G9

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

U01AI069924

Identifier Type: NIH

Identifier Source: secondary_id

View Link

GYNOCULAR

Identifier Type: -

Identifier Source: org_study_id