Cervix Cancer, Cervix Lesion
Conditions
Keywords
Thermocoagulation, Treatment, Cervical precancer
Brief summary
This was a prospective study to evaluate the short-term safety and acceptability of the Liger Medical thermal coagulation device for treatment of cervical precancerous lesions. Study results will inform the Honduras Ministry of Health regarding potential use of the Liger device for precancer treatment in Honduras and results may be of interest to other Latin American settings as well. The research was conducted in the Tegucigalpa Region in Honduras in 4 health facilities in urban and peri-urban settings. Participants were women ages 30-49 who met the study eligibility criteria. Human papilloma virus (HPV) and visual inspection with acetic acid (VIA)-positive women who were eligible for ablative treatment were offered thermal coagulation with the Liger instrument to treat their lesions and asked about acceptability of the treatment. At this visit, biopsies were also be taken. Women were followed-up at 1 month to evaluate short-term safety outcomes with a physical exam and receive their biopsy results. Depending on their biopsy results, they will be asked to return for repeat screening, referred for further treatment or asked to come back for a 12-month study visit. At the 12-month visit after treatment, women were followed up to evaluate cure rates. A second investigational device, Pocket Colposcope, was used to take cervix photos at the enrollment and 12-month study visit with participant consent. The photos were used to explore factors influencing treatment failure. De-identified photos and women's diagnosis information were also shared with the device developers, Duke University, for the purposes of improving their device. Women had the option to opt out of having cervix photos taken and still participate in the treatment portion of the study.
Interventions
DEVICELiger Medical Thermocoagulator
Thermocoagulation treatment by Liger Medical device (US FDA 510K clearance received)
Sponsors
Ashonplafa
Ministry of Health, Honduras
PATH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Thermal coagulator ablation treatment
Eligibility
Sex/Gender
FEMALE
Age
30 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
Women * Aged 30 to 49 years. * HPV and VIA positive. * Eligible for ablative treatment using World Health Organization Guidelines \[29\]. * The lesion covers \<75% of the cervix, the lesion does not enter the endocervical canal, the entire lesion can be visualized and covered by the Liger Medical Thermocoagulator probe, and there is no suspicion for invasive cancer.
Exclusion criteria
* Are pregnant or less than 3 months post-partum * Are not HPV and VIA positive * Do not have a cervical lesion that qualifies for ablative treatment * Have a bleeding disorder or taking anti-coagulant medication. * Do not give informed consent; or unable to provide the consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Short-term Safety Concerns for Ablative Treatment | 1 month after treatment | Reported a short-term adverse event. Note: Participants could report more than one discomfort or problem experienced. |
| Acceptability of Treatment by Women | Immediately after treatment | Level of pain women experienced during the thermal coagulation procedure will be calculated by the number and percent of women indicating minimal to worst possible levels of pain using the Wong-Baker FACES® pain rating scale. Women's acceptability will also be assessed by asking if they would recommend the Liger Thermocoagulator treatment to a friend or relative who needed similar treatment as well as reasons for her response. Wong-Baker FACES® pain rating scale: MINIMUM value: 0 (no hurt = best outcome) Value: 2 (hurts little bit) Value: 4 (hurts little more) Value: 6 (hurts even more) Value: 8 (hurts lot more) MAXIMUM value: 10 (hurts whole lot = worst outcome) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With no Evidence of CIN2-3 Lesions 12 Months After Thermal Coagulation | One time, 12 months after treatment | Percentage of participants with no evidence of cervical intraepithelial neoplasia grade 2 or grade 3 (CIN2-3) at 12 months, based on histological evaluation following the standard criteria from WHO Classification of Tumours, 5th Edition, Volume 4: Female Genital Tumours. |
| Treatment Failure | Once, 12 months after treatment | Qualitative analysis of cervical photos by an expert colposcopist to explore factors associated with treatment failure, compared characteristics of the cervix and precancerous lesions among women with CIN2-3 at Visit 1 (enrollment) in women whose treatment resulted in lesion disappearance (\<CIN2), and women with persistent lesions (CIN2-3) at 12 months. Adequacy of the image included focus, blur, and capture; a well focused image without obstructions (blood, cysts) that captured the whole ectocervix and cervical os was considered adequate. For squamous columnar junction and transformation zone (TZ) visibility, TZ1 signifies a fully visible TZ, TZ2 signifies the TZ or visible lesions extend into the cervical canal and the TZ covers more than 75% of the ectocervix, and TZ3 signifies that the TZ is not at all visible, in accordance with WHO recommendations. Baseline histology reports histological evaluation of lesions as cervical intraepithelial neoplasia grade 2 (CIN2) or 3 (CIN3). |
Countries
United States
Participant flow
Pre-assignment details
One woman was positive for visual inspection with acetic acid, but after enrollment was found to not have documentation of her human papillomavirus test or test result. Therefore, 320 were enrolled but only 319 participated in the study.
Participants by arm
| Arm | Count |
|---|---|
| Thermocoagulation Treatment Received thermal coagulation treatment for cervical precancer. | 319 |
| Total | 319 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Care outside study, ineligible to cont. | 3 |
| Overall Study | Moved away from study area | 4 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Thermocoagulation Treatment | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 319 Participants | — |
| Age, Continuous | 37.3 years STANDARD_DEVIATION 5.2 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Honduras | 319 participants | — |
| Sex: Female, Male Female | 319 Participants | — |
| Sex: Female, Male Male | 0 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 319 |
| other Total, other adverse events | 308 / 319 |
| serious Total, serious adverse events | 0 / 319 |
Outcome results
Primary
Acceptability of Treatment by Women
Level of pain women experienced during the thermal coagulation procedure will be calculated by the number and percent of women indicating minimal to worst possible levels of pain using the Wong-Baker FACES® pain rating scale. Women's acceptability will also be assessed by asking if they would recommend the Liger Thermocoagulator treatment to a friend or relative who needed similar treatment as well as reasons for her response. Wong-Baker FACES® pain rating scale: MINIMUM value: 0 (no hurt = best outcome) Value: 2 (hurts little bit) Value: 4 (hurts little more) Value: 6 (hurts even more) Value: 8 (hurts lot more) MAXIMUM value: 10 (hurts whole lot = worst outcome)
Time frame: Immediately after treatment
Population: Not applicable; all participants were included.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Thermocoagulation Treatment | Acceptability of Treatment by Women | FACES® level of pain: 0 - no hurt | 62 Participants |
| Thermocoagulation Treatment | Acceptability of Treatment by Women | FACES® level of pain: 2 - hurts little bit | 168 Participants |
| Thermocoagulation Treatment | Acceptability of Treatment by Women | FACES® level of pain: 4 - hurts little more | 43 Participants |
| Thermocoagulation Treatment | Acceptability of Treatment by Women | FACES® level of pain: 6 - hurts even more | 30 Participants |
| Thermocoagulation Treatment | Acceptability of Treatment by Women | FACES® level of pain: 8 - hurts whole lot | 15 Participants |
| Thermocoagulation Treatment | Acceptability of Treatment by Women | FACES® level of pain: 10 - hurts worst | 1 Participants |
| Thermocoagulation Treatment | Acceptability of Treatment by Women | Would recommend treatment to friend/relative | 319 Participants |
| Thermocoagulation Treatment | Acceptability of Treatment by Women | Would not recommend treatment to friend/relative | 0 Participants |
Primary
Short-term Safety Concerns for Ablative Treatment
Reported a short-term adverse event. Note: Participants could report more than one discomfort or problem experienced.
Time frame: 1 month after treatment
Population: All participants were included. Note: Participants could report more than one discomfort or problem experienced.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Thermocoagulation Treatment | Short-term Safety Concerns for Ablative Treatment | Colorless watery discharge | 288 participants |
| Thermocoagulation Treatment | Short-term Safety Concerns for Ablative Treatment | Brown/black discharge | 106 participants |
| Thermocoagulation Treatment | Short-term Safety Concerns for Ablative Treatment | Foul-smelling, pus-colored discharge | 100 participants |
| Thermocoagulation Treatment | Short-term Safety Concerns for Ablative Treatment | Bleeding | 31 participants |
| Thermocoagulation Treatment | Short-term Safety Concerns for Ablative Treatment | Pain while urinating | 2 participants |
| Thermocoagulation Treatment | Short-term Safety Concerns for Ablative Treatment | Severe lower abdominal pain | 11 participants |
| Thermocoagulation Treatment | Short-term Safety Concerns for Ablative Treatment | Fever | 0 participants |
Secondary
Percentage of Participants With no Evidence of CIN2-3 Lesions 12 Months After Thermal Coagulation
Percentage of participants with no evidence of cervical intraepithelial neoplasia grade 2 or grade 3 (CIN2-3) at 12 months, based on histological evaluation following the standard criteria from WHO Classification of Tumours, 5th Edition, Volume 4: Female Genital Tumours.
Time frame: One time, 12 months after treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thermocoagulation Treatment | Percentage of Participants With no Evidence of CIN2-3 Lesions 12 Months After Thermal Coagulation | 91.30 % participants |
| < CIN2 at Baseline | Percentage of Participants With no Evidence of CIN2-3 Lesions 12 Months After Thermal Coagulation | 97.96 % participants |
Secondary
Treatment Failure
Qualitative analysis of cervical photos by an expert colposcopist to explore factors associated with treatment failure, compared characteristics of the cervix and precancerous lesions among women with CIN2-3 at Visit 1 (enrollment) in women whose treatment resulted in lesion disappearance (\<CIN2), and women with persistent lesions (CIN2-3) at 12 months. Adequacy of the image included focus, blur, and capture; a well focused image without obstructions (blood, cysts) that captured the whole ectocervix and cervical os was considered adequate. For squamous columnar junction and transformation zone (TZ) visibility, TZ1 signifies a fully visible TZ, TZ2 signifies the TZ or visible lesions extend into the cervical canal and the TZ covers more than 75% of the ectocervix, and TZ3 signifies that the TZ is not at all visible, in accordance with WHO recommendations. Baseline histology reports histological evaluation of lesions as cervical intraepithelial neoplasia grade 2 (CIN2) or 3 (CIN3).
Time frame: Once, 12 months after treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Thermocoagulation Treatment | Treatment Failure | Location of the lesion: Inside the TZ | 4 Participants |
| Thermocoagulation Treatment | Treatment Failure | Location of the lesion: Outside the TZ | 0 Participants |
| Thermocoagulation Treatment | Treatment Failure | Squamous columnar junction visibility: TZ1 | 1 Participants |
| Thermocoagulation Treatment | Treatment Failure | Size of worst lesion (% coverage): 0-4 | 1 Participants |
| Thermocoagulation Treatment | Treatment Failure | Squamous columnar junction visibility: TZ2 | 1 Participants |
| Thermocoagulation Treatment | Treatment Failure | Mosaic of the worst lesion: Coarse | 2 Participants |
| Thermocoagulation Treatment | Treatment Failure | Baseline photo: Adequate | 2 Participants |
| Thermocoagulation Treatment | Treatment Failure | Mosaic of the worst lesion: No mosaic | 3 Participants |
| Thermocoagulation Treatment | Treatment Failure | Squamous columnar junction visibility: TZ3 | 2 Participants |
| Thermocoagulation Treatment | Treatment Failure | Mosaic of the worst lesion: Not evaluable | 0 Participants |
| Thermocoagulation Treatment | Treatment Failure | Location of the lesion: Not evaluable | 1 Participants |
| Thermocoagulation Treatment | Treatment Failure | Squamous columnar junction visibility: Missing | 1 Participants |
| Thermocoagulation Treatment | Treatment Failure | Border of the worst lesion: Sharp | 4 Participants |
| Thermocoagulation Treatment | Treatment Failure | Border of the worst lesion: Not evaluable | 1 Participants |
| Thermocoagulation Treatment | Treatment Failure | Baseline photo: Inadequate | 3 Participants |
| Thermocoagulation Treatment | Treatment Failure | Possible diagnosis: No lesion | 1 Participants |
| Thermocoagulation Treatment | Treatment Failure | Visible abnormal areas: 0 | 1 Participants |
| Thermocoagulation Treatment | Treatment Failure | Possible diagnosis: LSIL | 0 Participants |
| Thermocoagulation Treatment | Treatment Failure | Visible abnormal areas: 1 | 1 Participants |
| Thermocoagulation Treatment | Treatment Failure | Possible diagnosis: HSIL | 3 Participants |
| Thermocoagulation Treatment | Treatment Failure | Possible diagnosis: Not evaluable | 0 Participants |
| Thermocoagulation Treatment | Treatment Failure | Mosaic of the worst lesion: Fine | 0 Participants |
| Thermocoagulation Treatment | Treatment Failure | Baseline histology: CIN2 | 3 Participants |
| Thermocoagulation Treatment | Treatment Failure | Visible abnormal areas: 2+ | 1 Participants |
| Thermocoagulation Treatment | Treatment Failure | Baseline histology: CIN3 | 2 Participants |
| Thermocoagulation Treatment | Treatment Failure | Possible diagnosis: Invasion | 1 Participants |
| Thermocoagulation Treatment | Treatment Failure | Visible abnormal areas: Not evaluable | 0 Participants |
| Thermocoagulation Treatment | Treatment Failure | Size of worst lesion (% coverage): 5-50 | 2 Participants |
| Thermocoagulation Treatment | Treatment Failure | Border of the worst lesion: Irregular | 0 Participants |
| Thermocoagulation Treatment | Treatment Failure | Size of worst lesion (% coverage): >50 | 2 Participants |
| Thermocoagulation Treatment | Treatment Failure | Visible abnormal areas: Missing | 2 Participants |
| < CIN2 at Baseline | Treatment Failure | Size of worst lesion (% coverage): >50 | 18 Participants |
| < CIN2 at Baseline | Treatment Failure | Location of the lesion: Inside the TZ | 43 Participants |
| < CIN2 at Baseline | Treatment Failure | Border of the worst lesion: Sharp | 36 Participants |
| < CIN2 at Baseline | Treatment Failure | Baseline photo: Adequate | 38 Participants |
| < CIN2 at Baseline | Treatment Failure | Possible diagnosis: HSIL | 25 Participants |
| < CIN2 at Baseline | Treatment Failure | Possible diagnosis: Invasion | 15 Participants |
| < CIN2 at Baseline | Treatment Failure | Baseline photo: Inadequate | 25 Participants |
| < CIN2 at Baseline | Treatment Failure | Squamous columnar junction visibility: TZ1 | 20 Participants |
| < CIN2 at Baseline | Treatment Failure | Squamous columnar junction visibility: TZ2 | 4 Participants |
| < CIN2 at Baseline | Treatment Failure | Squamous columnar junction visibility: TZ3 | 39 Participants |
| < CIN2 at Baseline | Treatment Failure | Squamous columnar junction visibility: Missing | 0 Participants |
| < CIN2 at Baseline | Treatment Failure | Visible abnormal areas: 1 | 23 Participants |
| < CIN2 at Baseline | Treatment Failure | Visible abnormal areas: 2+ | 29 Participants |
| < CIN2 at Baseline | Treatment Failure | Visible abnormal areas: Not evaluable | 2 Participants |
| < CIN2 at Baseline | Treatment Failure | Visible abnormal areas: Missing | 1 Participants |
| < CIN2 at Baseline | Treatment Failure | Location of the lesion: Outside the TZ | 10 Participants |
| < CIN2 at Baseline | Treatment Failure | Location of the lesion: Not evaluable | 10 Participants |
| < CIN2 at Baseline | Treatment Failure | Mosaic of the worst lesion: Fine | 2 Participants |
| < CIN2 at Baseline | Treatment Failure | Mosaic of the worst lesion: Coarse | 7 Participants |
| < CIN2 at Baseline | Treatment Failure | Mosaic of the worst lesion: No mosaic | 50 Participants |
| < CIN2 at Baseline | Treatment Failure | Mosaic of the worst lesion: Not evaluable | 4 Participants |
| < CIN2 at Baseline | Treatment Failure | Border of the worst lesion: Irregular | 10 Participants |
| < CIN2 at Baseline | Treatment Failure | Border of the worst lesion: Not evaluable | 17 Participants |
| < CIN2 at Baseline | Treatment Failure | Possible diagnosis: No lesion | 12 Participants |
| < CIN2 at Baseline | Treatment Failure | Possible diagnosis: LSIL | 8 Participants |
| < CIN2 at Baseline | Treatment Failure | Possible diagnosis: Not evaluable | 3 Participants |
| < CIN2 at Baseline | Treatment Failure | Baseline histology: CIN2 | 32 Participants |
| < CIN2 at Baseline | Treatment Failure | Baseline histology: CIN3 | 31 Participants |
| < CIN2 at Baseline | Treatment Failure | Size of worst lesion (% coverage): 0-4 | 7 Participants |
| < CIN2 at Baseline | Treatment Failure | Size of worst lesion (% coverage): 5-50 | 38 Participants |
| < CIN2 at Baseline | Treatment Failure | Visible abnormal areas: 0 | 8 Participants |
p-value: 0.396Fisher Exact
p-value: 0.351Fisher Exact
p-value: 0.774Fisher Exact
p-value: 1Fisher Exact
p-value: 0.36Fisher Exact
p-value: 0.881Fisher Exact
p-value: 0.829Fisher Exact
p-value: 1Fisher Exact
p-value: 1Fisher Exact
p-value: 0.493Fisher Exact