Cervical Intraepithelial Neoplasia
Conditions
Brief summary
The purpose of this study is to compare the rate of recurrence of cervical intraepithelial neoplasia among HIV-positive women receiving cryotherapy versus LEEP over 2 years of follow-up and to compare the shedding of HIV-1 from the cervix between HIV-positive women receiving cryotherapy versus LEEP over 3 weeks of follow-up.
Detailed description
The recent scale-up of antiretroviral treatment programs in resource-limited settings provides an unprecedented opportunity to implement a comprehensive cervical cancer screening and treatment program for women who, by virtue of having HIV, are at significant risk for cervical disease. Unfortunately, even if screening is offered free of charge to millions of women living with HIV, it is unclear which treatment modality for pre-cancerous cervical lesions will be most effective since HIV appears to affect outcomes of treatment by increasing the recurrence and severity of cervical disease. Cervical treatment may also increase shedding of HIV from the cervix which may put discordant couples at risk and possibly spread HIV more widely. This study proposes to randomize HIV-positive women with cervical intraepithelial neoplasia grade 2 and 3 (CIN 2 and 3) to cryotherapy vs. loop electrosurgical excision procedure (LEEP) and measure the recurrence of cervical disease in each group over 2-years of follow-up as well as HIV shedding from the cervix for 6 weeks after treatment. Our hypothesis is that compared to cryotherapy, LEEP is significantly more likely to prevent recurrence of cervical lesions over 2 years of follow-up and less likely to cause shedding of HIV-1 from the cervix over 3 weeks of follow-up.
Interventions
LEEP procedure uses a low-voltage electrified wire loop to cut out diseased part of cervix
PROCEDURECryotherapy
Cryotherapy procedure involves using a cryoprobe and carbon dioxide or nitrous oxide gas to freeze the diseased part of the cervix
Sponsors
University of Nairobi
International Agency for Research on Cancer
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV positive receiving care at the Coptic Hope Center * Not pregnant by clinical examination or history * Have an intact cervix * Have not received prior cervical treatment * Do not have a history of a bleeding disorder * Are above 18 years of age
Exclusion criteria
* HIV-negative * Male * Below 18 years of age * Pregnant by clinical examination or history * Post-hysterectomy * Post-cervical cancer treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence of Cervical Intraepithelial Neoplasia Among HIV-positive Women | 2 years | Rate of recurrence of cervical intraepithelial neoplasia among HIV-positive women receiving cryotherapy versus LEEP over 2 years of follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Shedding of HIV-1 From the Cervix Between HIV-positive Women | 3 weeks | Shedding of HIV-1 from the cervix between HIV-positive women receiving cryotherapy versus LEEP between baseline and weeks 1, 2, and 3 of follow-up |
Countries
Kenya
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cryotherapy Cryotherapy procedure involves using a cryoprobe and carbon dioxide or nitrous oxide gas to freeze the diseased part of the cervix
Cryotherapy: Cryotherapy procedure involves using a cryoprobe and carbon dioxide or nitrous oxide gas to freeze the diseased part of the cervix | 200 |
| Loop Electrosurgical Excision Procedure Loop Electrosurgical Excision Procedure (LEEP) uses a low-voltage electrified wire loop to cut out diseased part of cervix
Loop Electrosurgical Excision Procedure (LEEP): LEEP procedure uses a low-voltage electrified wire loop to cut out diseased part of cervix | 200 |
| Total | 400 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 5 | 3 |
| Overall Study | Lost to Follow-up | 6 | 14 |
| Overall Study | Referred for further management | 16 | 15 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Cryotherapy | Loop Electrosurgical Excision Procedure | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 194 Participants | 189 Participants | 383 Participants |
| Age, Continuous | 38.2 years | 37.4 years | 37.4 years |
| Previously screened for cervical cancer | 65 Participants | 55 Participants | 120 Participants |
| Region of Enrollment Kenya | 200 Participants | 200 Participants | 400 Participants |
| Sex: Female, Male Female | 200 Participants | 200 Participants | 400 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 | — / — | — / — |
| other Total, other adverse events | 2 / 200 | 0 / 200 |
| serious Total, serious adverse events | 5 / 200 | 2 / 200 |
Outcome results
Primary
Recurrence of Cervical Intraepithelial Neoplasia Among HIV-positive Women
Rate of recurrence of cervical intraepithelial neoplasia among HIV-positive women receiving cryotherapy versus LEEP over 2 years of follow-up
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cryotherapy | Recurrence of Cervical Intraepithelial Neoplasia Among HIV-positive Women | 60 Participants |
| Loop Electrosurgical Excision Procedure | Recurrence of Cervical Intraepithelial Neoplasia Among HIV-positive Women | 37 Participants |
Secondary
Shedding of HIV-1 From the Cervix Between HIV-positive Women
Shedding of HIV-1 from the cervix between HIV-positive women receiving cryotherapy versus LEEP between baseline and weeks 1, 2, and 3 of follow-up
Time frame: 3 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cryotherapy | Shedding of HIV-1 From the Cervix Between HIV-positive Women | Baseline and Week 1 | -0.02 change in log10 cps HIV RNA per swab |
| Cryotherapy | Shedding of HIV-1 From the Cervix Between HIV-positive Women | Baseline and Week 3 | 0.05 change in log10 cps HIV RNA per swab |
| Cryotherapy | Shedding of HIV-1 From the Cervix Between HIV-positive Women | Baseline and Week 2 | 0.07 change in log10 cps HIV RNA per swab |
| Loop Electrosurgical Excision Procedure | Shedding of HIV-1 From the Cervix Between HIV-positive Women | Baseline and Week 1 | 0.10 change in log10 cps HIV RNA per swab |
| Loop Electrosurgical Excision Procedure | Shedding of HIV-1 From the Cervix Between HIV-positive Women | Baseline and Week 2 | 0.25 change in log10 cps HIV RNA per swab |
| Loop Electrosurgical Excision Procedure | Shedding of HIV-1 From the Cervix Between HIV-positive Women | Baseline and Week 3 | 0.26 change in log10 cps HIV RNA per swab |