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

HIV/AIDS Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03931083
• Other study ID #: GYNOCULAR
• Secondary ID: KFS-4156-02-2017
• Status: Recruiting
• Start date: May 8, 2019
• Est. completion date: December 1, 2022

Study information

• Verified date: October 2020
• Source: University of Bern
• Contact: Katayoun Taghavi, MD
• Phone: +41 31 631 35 23
• Email: katayoun.taghavi[@]ispm.unibe.ch
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: December 1, 2022
• Est. primary completion date: January 1, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• HIV/AIDS
• Uterine Cervical Neoplasms

Intervention

Diagnostic Test:
• 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.

Locations

Country	Name	City	State
Zambia	Centre for Infectious Disease Research in Zambia	Lusaka

Sponsors (4)

Lead Sponsor	Collaborator
University of Bern	Centre for Infectious Disease Research in Zambia, Cervical Cancer Prevention Program in Zambia, International Agency for Research on Cancer

Country where clinical trial is conducted

Zambia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety outcomes: For each adverse event found the investigators will calculate crude frequencies	Adverse events will be recorded. The investigators will ask participants to inform the study nurse or assistant if they develop any of these, in person or by phone. Given the health system in this context is not centralized, it is most efficient to ask participants to report these to the clinical team and investigators. Information describing these events will include: time of onset, duration, resolution, action to be taken, assessment of intensity, relationship with study treatment. The clinical team will also complete assessments of seriousness, causality and expectedness. Participants are asked to inform the clinical team immediately if any AE occur in the 9 months following their initial enrolment. At each visit, the Study nurse/assistant will also inquire about any adverse events that have occurred, for verification. For each adverse event found the investigators will calculate crude frequencies.	9 months
Primary	Test accuracy (sensitivity, specificity) of the Gynocular™ when used as stand-alone tests to detect CIN2+	To estimate the sensitivity and specificity of the Gynocular when used as a standalone tests to detect CIN2+ among WLHIV.	6 months
Primary	Test accuracy (sensitivity, specificity) of HR-HPV when used as stand-alone tests to detect CIN2+	To estimate the sensitivity and specificity of HR-HPV when used as a standalone tests to detect CIN2+ among WLHIV.	6 months
Primary	Test accuracy (sensitivity, specificity) of VIA when used as stand-alone tests to detect CIN2+	To estimate the sensitivity and specificity of VIA when used as a standalone tests to detect CIN2+ among WLHIV.	6 months
Secondary	Diagnostic test accuracy of the Gynocular™to detect CIN2+/HSIL: other estimates, stand alone	To determine other estimates of test accuracy of the Gynocular™ (including positive and negative predictive values, positive and negative likelihood ratios, false positive rate, false negative rate, number needed to screen and area under the ROC curve (AUC).	6 months
Secondary	Diagnostic test accuracy of HR-HPV testing to detect CIN2+/HSIL: other estimates, stand alone	To determine other estimates of HR-HPV testing test accuracy (including positive and negative predictive values, positive and negative likelihood ratios, false positive rate, false negative rate, number needed to screen and area under the ROC curve (AUC).	6 months
Secondary	Diagnostic test accuracy of VIA to detect CIN2+/HSIL: other estimates, stand alone	To determine other estimates of VIA test accuracy (including positive and negative predictive values, positive and negative likelihood ratios, false positive rate, false negative rate, number needed to screen and area under the ROC curve (AUC).	6 months
Secondary	Diagnostic test accuracy of HR-HPV testing followed by Gynocular™ to detect CIN2+/HSIL: test combination	To determine estimates of test accuracy for combinations of screening tests, i.e. HR-HPV followed by Gynocular™	6 months
Secondary	Diagnostic test accuracy of HR-HPV testing followed by Gynocular™ to detect CIN2+/HSIL: test combination - subgroup analyses	To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses	6 months
Secondary	Diagnostic test accuracy of the Gynocular™ followed by HR-HPV testing to detect CIN2+/HSIL: test combination	To determine estimates of test accuracy for combinations of screening tests, i.e. Gynocular™ followed by HR-HPV	6 months
Secondary	Diagnostic test accuracy of the Gynocular™ followed by HR-HPV testing to detect CIN2+/HSIL: test combination subgroup analyses	To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses	6 months
Secondary	Diagnostic test accuracy VIA followed by Gynocular™ to detect CIN2+/HSIL: test combination	To determine estimates of test accuracy for combinations of screening tests, i.e. VIA followed by Gynocular™	6 months
Secondary	Diagnostic test accuracy VIA followed by Gynocular™ to detect CIN2+/HSIL: test combination - subgroup analyses	To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses	6 months
Secondary	Diagnostic test accuracy of the Gynocular™ followed by VIA to detect CIN2+/HSIL: test combination	To determine estimates of test accuracy for combinations of screening tests, i.e. Gynocular™ followed by VIA	6 months
Secondary	Diagnostic test accuracy of the Gynocular™ followed by VIA to detect CIN2+/HSIL: test combination - subgroup analyses	To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses	6 months
Secondary	Diagnostic test accuracy of the HR-HPV followed by VIA to detect CIN2+/HSIL: test combination	To determine estimates of test accuracy for combinations of screening tests: HR-HPV followed by VIA.	6 months
Secondary	Diagnostic test accuracy of the HR-HPV followed by VIA to detect CIN2+/HSIL: test combination - subgroup analyses	To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses	6 months
Secondary	Diagnostic test accuracy of the VIA followed by HR-HPV to detect CIN2+/HSIL: test combination	To determine estimates of test accuracy for combinations of screening tests: VIA followed by HR-HPV.	6 months
Secondary	Diagnostic test accuracy of the VIA followed by HR-HPV to detect CIN2+/HSIL: test combination subgroup analyses	To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses	6 months
Secondary	Subgroup analyses for the diagnostic test accuracy of Gynocular™: stand alone test	To investigate the effects of a age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses.	6 months
Secondary	Subgroup analyses for the diagnostic test accuracy of VIA: stand alone test	To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses.	6 months
Secondary	Subgroup analyses for the diagnostic test accuracy of HR-HPV testing: stand alone test	To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses	6 months
Secondary	Subgroup analyses for the diagnostic test accuracy of VIA, HR-HPV testing and Gynocular™: Combined tests	To investigate the effects of age, menopause, parity, ART status, HIV RNA, education, contraception, CD4 cell count, previous treatment for precancerous disease and sexually transmitted infections (STIs) on test accuracy of test combination in subgroup analyses	6 months
Secondary	Investigation of Swede Score in WLHIV	Area under the receiver operating characteristic (ROC) curve for Swede score determined by Gynocular™ in WLHIV	6 months
Secondary	Investigation of co-infections of premalignant and malignant disease (STIs/HR-HPV)	Descriptive analysis of the STI and HR-HPV type distribution associated with each stage of CIN, and when there is persistent disease in WLHIV.	6 months
Secondary	Investigation of Trichomonas vaginalis prevalence and persistence in association with menstrual hygiene practices	Descriptive analysis of the prevalence and persistence of Trichomonas vaginalis in association with vaginal and menstrual hygiene practices.	6 months
Secondary	Investigations to inform telemedicine capacity: Comparison of image quality	Description of image quality from static assessors, in terms of the assessors' ability to adequately evaluate the images.	6 months
Secondary	Investigations to inform telemedicine capacity: use of static images	Proportion of correctly diagnosed CIN2+ through static images obtained by the Gynocular™.	6 months
Secondary	Investigations to inform telemedicine capacity: ROC curve for Swede score	Area under the ROC for static image Swede score obtained by Gynocular™ in WLHIV.	6 months
Secondary	Investigations to inform telemedicine capacity: Live versus static assessors	Cohen's kappa coefficient to assess agreement between live and static assessors.	6 months
Secondary	Artificial Intelligence (AI) for improving the detection of precancerous cervical lesions: testing AI algorithm	Test accuracies of AI deep learning tool retrospectively using coded images obtained in the study through the Gynocular™ and smartphone.	6 months
Secondary	Artificial Intelligence for improving the detection of precancerous cervical lesions: improve AI algorithm	Inform and improve AI deep learning tools to detect HSIL by using images or GIFs obtained in the study through the Gynocular™ and smartphone.	6 months
Secondary	Diagnostic test accuracy of AI tool to detect CIN2+/HSIL: other estimates, stand alone	To estimate the sensitivity and specificity of HR-HPV when used as a standalone tests to detect CIN2+/HSIL among WLHIV.	6 months
Secondary	Diagnostic test accuracy of HR-HPV testing followed by AI tool to detect CIN2+/HSIL: test combination	To determine estimates of test accuracy for combinations of screening tests, i.e. HR-HPV followed by AI tool	6 months