CIN 2/3, HPV Infection, Human Immunodeficiency Virus
Conditions
Brief summary
The purpose of this study is to evaluate the safety, acceptability, and efficacy of Thermocoagulation for treatment of precancerous lesions among HIV-positive women in a screen-and-treat program in Western Kenya.
Detailed description
Thermocoagulation is endorsed as an alternative to Cryotherapy for treatment of Visual Inspection with Acetic Acid (VIA) or Human Papillomavirus (HPV)-positive women by the 2018 Kenya national cancer guidelines.32 Data primary from Western countries demonstrate similar efficacy for the treatment of precancerous lesions between Cryotherapy and Thermocoagulation. Data on safety, acceptability, and efficacy, particularly linked to gold-standard pathology, among HIV-positive women in low-resource settings are scare. Given the demonstrated benefits over cryotherapy including increased portability and availability hence easier implementation, use of thermal coagulation for the treatment of precancerous lesions in low resource settings could significantly improve access to treatment compared with cryotherapy. This study seeks to fill a critical data gap by evaluating the efficacy of thermocoagulation among HIV-positive positive women using gold-standard biopsy for disease verification at baseline and follow-up, as indicated. We will also assess the safety and acceptability of this treatment modality among patients and providers Aim 1: To evaluate the efficacy of thermal coagulation for the treatment of HIV-positive, HPV-positive women by assessing rates of HPV persistence and CIN2/3 rate at 12 months after treatment Aim 2: To evaluate the safety and acceptability of thermal coagulation for treatment of abnormal cervical lesions within a screen-and-treat program among HIV-positive women in Western Kenya. Aim 3: Evaluate provider acceptability of thermal coagulation for the treatment of precancerous cervical lesion within a screen-and-treat program in Western Kenya. Outline: Counseling on HPV, cervical cancer, and the screening process was offered during routine HIV clinics in group and individual settings. Participants will then be provided self-sampling instructions, a collection kit, and a private area to perform self-collection. The self-collected HPV samples will be labeled, stored, and processed for DNA of 14 high-risk HPV types. HPV-positive participants were invited for a return visit, including a pelvic examination and visual inspection with acetic acid (VIA) to determine eligibility for ablative therapy. After ablation, a questionnaire will be administered to participants to evaluate treatment experience. All participants will be given a 4- to 6-week phone or in-person follow-up appointment, per participant preference
Interventions
DEVICEThermocoagulation
Treatment of positive screening results will be performed using the Liger Thermocoagulator device
Sponsors
National Institutes of Health (NIH)
Fogarty International Center of the National Institute of Health
University of California, San Francisco
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
25 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age 25-65 years. 2. Enrolled in HIV care at FACES-supported clinics in Kisumu County. 3. Able to understand a written informed consent document, and willing to sign it. 4. Speaks a language that the consent form and data collection instruments are written in.
Exclusion criteria
1. Has a history of cervical cancer. 2. Has received any treatment for cervical precancer after screening positive for precancer. 3. Has evidence of cervical infection. 4. Pregnant women are excluded from this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With no Evidence of Cervical Dysplasia at 12-months | 12 months | The proportion of participants with no evidence of cervical dysplasia at 12-months follow-up, defined as biopsy-confirmed CIN1 result or normal findings, 12-months following treatment. |
| Proportion of Participants With Persistent HPV at 12-month Follow-up | 12 months | The proportion of persistence of HPV at follow-up will be reported defined as treatment failure with persistent biopsy-confirmed CIN2/3. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Pain Score Category | Day of Treatment, approximately 1 day | A 4-point Visual Analog Scale (VAS) for pain assessment was used to evaluate pain immediately after treatment. The pain VAS was comprised of verbal descriptors, one for each symptom extreme. The pain VAS is self-completed by the respondent. The respondent is asked to select the point that represents their pain intensity. The no pain anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater pain intensity. The following cut points on the pain VAS have been recommended: no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and severe pain (75- 100 mm). |
| Percentage of Participants Reporting Treatment-related Adverse Events (AE) | Up to 6 weeks following treatment | The percentage of participants reporting grade 2 and higher AEs, and severe adverse events (SAEs) during the 4-week follow-up will be reported by event. |
| Frequency of Positive Participant Satisfaction Responses | Up to 6 weeks following treatment | Participant satisfaction with thermocoagulation will be evaluated by determining the proportion of participants indicating a response of 'yes' to the question Do you feel satisfied with the treatment you received? with an alternative response of 'no' at the 4-6 week follow-up visit. |
Countries
Kenya
Participant flow
Recruitment details
Between August 2019 and February 2020, women enrolled in care at Fostering Advances through Collaboration, Education & Sciences (FACES)- supported HIV clinics in western Kenya were recruited to the study.
Pre-assignment details
All participants received cervical cancer screening using human papillomavirus (HPV) testing. Participants with positive results received a biopsy and then proceeded to same-day treatment. Thermocoagulation candidates must have a fully visualized, squamocolumnar junction, cervical lesions (if present) covering \< 75% of cervix, and no endocervical component of lesion, or suspicion for cancer. Participants who were not candidates for ablation were referred to a nearby facility.
Participants by arm
| Arm | Count |
|---|---|
| Thermocoagulation Thermal ablation of cervix for treatment of CIN2/3 among HIV-positive participants will be performed by a trained, non-physician clinician. Thermocoagulation will last approximately 20 seconds and will be performed using the Liger Thermocoagulator device | 293 |
| Total | 293 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| 12 Month Follow-up | Pathology results for 12 month treatment efficacy not available for these participants | 4 |
| Screening & Thermocoagulation (Ablation) | Not considered candidates for thermocoagulation | 86 |
Baseline characteristics
| Characteristic | Thermocoagulation |
|---|---|
| Age, Continuous | 40.4 years STANDARD_DEVIATION 8.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 293 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Prior cervical cancer screening | 206 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 293 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Kenya | 293 participants |
| Sex: Female, Male Female | 293 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 293 |
| other Total, other adverse events | 262 / 293 |
| serious Total, serious adverse events | 0 / 293 |
Outcome results
Primary
Proportion of Participants With no Evidence of Cervical Dysplasia at 12-months
The proportion of participants with no evidence of cervical dysplasia at 12-months follow-up, defined as biopsy-confirmed CIN1 result or normal findings, 12-months following treatment.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thermocoagulation | Proportion of Participants With no Evidence of Cervical Dysplasia at 12-months | 0.66 proportion of participants |
Primary
Proportion of Participants With Persistent HPV at 12-month Follow-up
The proportion of persistence of HPV at follow-up will be reported defined as treatment failure with persistent biopsy-confirmed CIN2/3.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thermocoagulation | Proportion of Participants With Persistent HPV at 12-month Follow-up | 0.34 proportion of participants |
Secondary
Frequency of Pain Score Category
A 4-point Visual Analog Scale (VAS) for pain assessment was used to evaluate pain immediately after treatment. The pain VAS was comprised of verbal descriptors, one for each symptom extreme. The pain VAS is self-completed by the respondent. The respondent is asked to select the point that represents their pain intensity. The no pain anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater pain intensity. The following cut points on the pain VAS have been recommended: no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and severe pain (75- 100 mm).
Time frame: Day of Treatment, approximately 1 day
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Thermocoagulation | Frequency of Pain Score Category | No pain | 15 Participants |
| Thermocoagulation | Frequency of Pain Score Category | Mild pain | 231 Participants |
| Thermocoagulation | Frequency of Pain Score Category | Moderate pain | 42 Participants |
| Thermocoagulation | Frequency of Pain Score Category | Severe pain | 5 Participants |
Secondary
Frequency of Positive Participant Satisfaction Responses
Participant satisfaction with thermocoagulation will be evaluated by determining the proportion of participants indicating a response of 'yes' to the question Do you feel satisfied with the treatment you received? with an alternative response of 'no' at the 4-6 week follow-up visit.
Time frame: Up to 6 weeks following treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Thermocoagulation | Frequency of Positive Participant Satisfaction Responses | 292 Participants |
Secondary
Percentage of Participants Reporting Treatment-related Adverse Events (AE)
The percentage of participants reporting grade 2 and higher AEs, and severe adverse events (SAEs) during the 4-week follow-up will be reported by event.
Time frame: Up to 6 weeks following treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Thermocoagulation | Percentage of Participants Reporting Treatment-related Adverse Events (AE) | Bleeding | 4 percentage of participants |
| Thermocoagulation | Percentage of Participants Reporting Treatment-related Adverse Events (AE) | Vaginal Discharge | 51.2 percentage of participants |
| Thermocoagulation | Percentage of Participants Reporting Treatment-related Adverse Events (AE) | Pelvic Pain | 19.6 percentage of participants |
| Thermocoagulation | Percentage of Participants Reporting Treatment-related Adverse Events (AE) | Participants with Grade 3 or 4 adverse events | 0 percentage of participants |