Cervical Cancer, HIV Infections, HPV Infection
Conditions
Keywords
Visual inspection with acetic acid (VIA)
Brief summary
The purpose of this study is to assess completion and performance of the following novel invasive cervical cancer (ICC) screen-and-treat algorithm among 625 HIV-positive women in Lilongwe, Malawi: 1) rapid testing of self-collected vaginal brush for primary high risk (hr)-human papillomavirus (HPV), 2) same-day visual inspection with acetic acid (VIA) for women who are hr-HPV positive, and 3) thermocoagulation for VIA positive/ablation-eligible (by cervical colposcopy) women.
Detailed description
This is a single arm, prospective study of 1,250 women (625 HIV-positive and 625 HIV-negative) enrolled from outpatient clinics that provide sexual and reproductive health (SRH) services and/or HIV care services in Lilongwe, Malawi. The primary objectives of this study are to assess completion of a novel ICC screen-and-treat strategy among HIV-positive women in Lilongwe, Malawi, using self-collected vaginal brush for hr-HPV testing, followed by same-day NIA and thermocoagulation for HPV-positive/NIA-positive/ablation-eligible (by colposcopy) women, and to determine the 24-week efficacy of thermocoagulation among HIV-positive women with CIN2/3. The secondary objective will be to evaluate the performance of the ICC screen-and-treat strategy by estimating overtreatment for women who are HPV-positive/NIA-positive/ablation-eligible, and undertreatment among HPV-positive/NIA-negative women.
Interventions
PROCEDUREVIA and thermocoagulation
Participants will self-collect a vaginal brush for hr-HPV testing. HPV-positive women and every 10th consecutive HPV-negative woman will complete same-day VIA with colposcopically-directed cervical biopsy and ECC (if lesion seen), and thermocoagulation if ablation-eligible by colposcopy. If no lesion is seen on colposcopy, the woman will have a cervical pap smear and ECC collected, and no thermocoagulation will be performed. Finally, women who are suspicious for cancer at VIA will undergo colposcopically-directed cervical biopsies.
Sponsors
National Cancer Institute (NCI)
United States Agency for International Development (USAID)
UNC Lineberger Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
25 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Females ≥ 25 years of age at study entry and ≤ 50 years of age (per current Malawi National Cervical Cancer Control Program guidelines for screening). 2. Ability and willingness of participant to provide written informed consent.
Exclusion criteria
1. Current or prior history of cervical, vaginal, or vulvar cancer or dysplasia 2. Current symptomatic sexually transmitted infection requiring treatment (women will be allowed to be in the study upon successful treatment) 3. Prior HPV vaccination. 4. Participants with known allergy to acetic acid. 5. Participants with a history of total hysterectomy. 6. Participants who are pregnant or plan on becoming pregnant during the study period. 7. Participants who are less than 12 weeks postpartum. 8. Participants with other illnesses that would limit compliance with study requirements or in the opinion of the investigator or designee, have a problem that would make participation in the study unsafe or complicate interpretation of study findings.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Same-day Visual Inspection With Acetic Acid (VIA) Rate | Baseline | The proportion of women who were HPV-positive and underwent same-day VIA following self-collected vaginal sampling was assessed, including both HIV-positive and HIV-negative participants. As per the study protocol, data were not stratified by HIV status for this outcome due to lack of scientific rationale for a difference in same-day VIA completion by HIV status. |
| Same-day Thermocoagulation Rate Among Women Who Were HPV-positive and Ablation-eligible by Colposcopy Triage | Baseline | Among women who tested HPV-positive through primary screening, those eligible for thermocoagulation by colposcopy triage received thermocoagulation treatment on the same day as self-collection. As specified in the study protocol, data were not stratified by HIV status for this outcome due to lack of scientific rationale for a difference in same-day colposcopy completion by HIV status. |
| High Risk (hr)-Human Papillomavirus (HPV) Positive Rate | Baseline | The proportion of women who tested High risk (hr)-human papillomavirus (HPV) positive on a self-collected vaginal brush among enrolled participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HPV Screen-triage-treat Algorithm for Cervical Cancer Screening | Up to 24 weeks | To evaluate the performance of the proposed ICC screen-and-treat strategy for cervical carcinoma screening among women who are HIV- positive, the rates of overtreatment and undertreatment rates were estimated. Overtreatment for women who are HPV-positive VIA- positive/ablation-eligible and would have received thermocoagulation but had no cervical precancer (i.e., high-grade cervical intraepithelial neoplasia), and undertreatment among HPV-positive with high-grade cervical intraepithelial neoplasia but were VIA-positive and eligible for thermocoagulation, and those who were VIA-negative. |
Countries
Malawi
Participant flow
Recruitment details
Participants were recruited from health facilities with outpatient clinics that provide sexual and reproductive health services and/or HIV care services in Lilongwe, Malawi between 6/24/2020- 2/28/2022. The first participant was enrolled on 6/24/2020, and the last participant was enrolled on 2/28/2022.
Pre-assignment details
Participants were assigned HIV-positive or HIV-negative groups based on HIV testing result.
Participants by arm
| Arm | Count |
|---|---|
| HIV Positive Women living with HIV | 625 |
| HIV Negative Women living without HIV | 625 |
| Total | 1,250 |
Baseline characteristics
| Characteristic | HIV Positive | HIV Negative | Total |
|---|---|---|---|
| Age, Continuous | 36 years | 33 years | 35 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 625 Participants | 625 Participants | 1250 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Level of education No education | 94 Participants | 39 Participants | 133 Participants |
| Level of education Primary | 344 Participants | 305 Participants | 649 Participants |
| Level of education Secondary | 172 Participants | 245 Participants | 417 Participants |
| Level of education Tertiary | 15 Participants | 36 Participants | 51 Participants |
| Marital status Married/Living with partner | 395 Participants | 475 Participants | 870 Participants |
| Marital status Never married | 9 Participants | 29 Participants | 38 Participants |
| Marital status Widowed/divorced/separated | 221 Participants | 121 Participants | 342 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 625 Participants | 625 Participants | 1250 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Malawi | 625 participants | 625 participants | 1250 participants |
| Sex: Female, Male Female | 625 Participants | 625 Participants | 1250 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 22 | 0 / 28 |
| other Total, other adverse events | 19 / 22 | 21 / 28 |
| serious Total, serious adverse events | 0 / 22 | 0 / 28 |
Outcome results
Primary
High Risk (hr)-Human Papillomavirus (HPV) Positive Rate
The proportion of women who tested High risk (hr)-human papillomavirus (HPV) positive on a self-collected vaginal brush among enrolled participants.
Time frame: Baseline
Population: Participants joined the study and provided self-collected vaginal samples using a Viba-Brush® for HPV testing.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HPV Positive | High Risk (hr)-Human Papillomavirus (HPV) Positive Rate | 295 Participants |
| HIV Negative | High Risk (hr)-Human Papillomavirus (HPV) Positive Rate | 181 Participants |
Primary
Same-day Thermocoagulation Rate Among Women Who Were HPV-positive and Ablation-eligible by Colposcopy Triage
Among women who tested HPV-positive through primary screening, those eligible for thermocoagulation by colposcopy triage received thermocoagulation treatment on the same day as self-collection. As specified in the study protocol, data were not stratified by HIV status for this outcome due to lack of scientific rationale for a difference in same-day colposcopy completion by HIV status.
Time frame: Baseline
Population: Participants who underwent HPV-based primary screening for cervical cancer and tested HPV-positive and were eligible for thermocoagulation by colposcopy triage and had thermocoagulation performed on the same day of self-collection.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HPV Positive | Same-day Thermocoagulation Rate Among Women Who Were HPV-positive and Ablation-eligible by Colposcopy Triage | HPV-positive participants eligible for thermocoagulation based on colposcopy triage | 110 Participants |
| HPV Positive | Same-day Thermocoagulation Rate Among Women Who Were HPV-positive and Ablation-eligible by Colposcopy Triage | Thermocoagulation completed among HPV-positive participants on same day of self-collection | 109 Participants |
Primary
Same-day Visual Inspection With Acetic Acid (VIA) Rate
The proportion of women who were HPV-positive and underwent same-day VIA following self-collected vaginal sampling was assessed, including both HIV-positive and HIV-negative participants. As per the study protocol, data were not stratified by HIV status for this outcome due to lack of scientific rationale for a difference in same-day VIA completion by HIV status.
Time frame: Baseline
Population: Participants who underwent HPV-based primary screening for cervical cancer and tested HPV-positive on self-collected vaginal sample and had VIA triage performed on the same day of self-collection.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HPV Positive | Same-day Visual Inspection With Acetic Acid (VIA) Rate | Visual Inspection with Acetic Acid (VIA) performed | 469 Participants |
| HPV Positive | Same-day Visual Inspection With Acetic Acid (VIA) Rate | Visual Inspection with Acetic Acid (VIA) performed on the same day | 459 Participants |
Secondary
HPV Screen-triage-treat Algorithm for Cervical Cancer Screening
To evaluate the performance of the proposed ICC screen-and-treat strategy for cervical carcinoma screening among women who are HIV- positive, the rates of overtreatment and undertreatment rates were estimated. Overtreatment for women who are HPV-positive VIA- positive/ablation-eligible and would have received thermocoagulation but had no cervical precancer (i.e., high-grade cervical intraepithelial neoplasia), and undertreatment among HPV-positive with high-grade cervical intraepithelial neoplasia but were VIA-positive and eligible for thermocoagulation, and those who were VIA-negative.
Time frame: Up to 24 weeks
Population: Participants who tested HPV-positive for cervical cancer screening in the study and completed the screen-triage-treat algorithm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HPV Positive | HPV Screen-triage-treat Algorithm for Cervical Cancer Screening | 49 Participants |
| HIV Negative | HPV Screen-triage-treat Algorithm for Cervical Cancer Screening | 10 Participants |
| HIV Positive, HPV Negative, VIA Positive | HPV Screen-triage-treat Algorithm for Cervical Cancer Screening | 0 Participants |