Cryotherapy vs. LEEP to Treat Cervical Intraepithelial Neoplasia (CIN) 2/3 Among HIV-positive Women (PHE-LEEP)

Impact of Cryotherapy Versus Loop Electrosurgical Excision Procedure (LEEP) on Recurrence of Cervical Intraepithelial Neoplasia and HIV-1 Cervical Shedding Among HIV-positive Women

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.

Study Overview

• Status: Completed
• Conditions: Cervical Intraepithelial Neoplasia
• Intervention / Treatment: Procedure: Cryotherapy; Procedure: Loop Electrosurgical Excision Procedure (LEEP)

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.

• Study Type: Interventional
• Enrollment (Actual): 400
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Kenya
  • Nairobi, Kenya, 21570-00505
    • Coptic Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cryotherapy; Cryotherapy procedure involves using a cryoprobe and carbon dioxide or nitrous oxide gas to freeze the diseased part of the cervix	Procedure: Cryotherapy; Cryotherapy procedure involves using a cryoprobe and carbon dioxide or nitrous oxide gas to freeze the diseased part of the cervix
Experimental: Loop Electrosurgical Excision Procedure; Loop Electrosurgical Excision Procedure (LEEP) uses a low-voltage electrified wire loop to cut out diseased part of cervix	Procedure: Loop Electrosurgical Excision Procedure (LEEP); LEEP procedure uses a low-voltage electrified wire loop to cut out diseased part of cervix; Other Names: LEEP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	3 weeks

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: University of Nairobi; International Agency for Research on Cancer
• Investigators: Principal Investigator: Michael Chung, MD, University of Washington

Publications and helpful links

General Publications

• Chung MH, De Vuyst H, Greene SA, Mugo NR, Querec TD, Nyongesa-Malava E, Cagle A, Sakr SR, Luchters S, Temmerman M, Unger ER, McGrath CJ. Human Papillomavirus Persistence and Association With Recurrent Cervical Intraepithelial Neoplasia After Cryotherapy vs Loop Electrosurgical Excision Procedure Among HIV-Positive Women: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2021 Oct 1;7(10):1514-1520. doi: 10.1001/jamaoncol.2021.2683.
• Greene SA, De Vuyst H, John-Stewart GC, Richardson BA, McGrath CJ, Marson KG, Trinh TT, Yatich N, Kiptinness C, Cagle A, Nyongesa-Malava E, Sakr SR, Mugo NR, Chung MH. Effect of Cryotherapy vs Loop Electrosurgical Excision Procedure on Cervical Disease Recurrence Among Women With HIV and High-Grade Cervical Lesions in Kenya: A Randomized Clinical Trial. JAMA. 2019 Oct 22;322(16):1570-1579. doi: 10.1001/jama.2019.14969.
• Greene SA, McGrath CJ, Lehman DA, Marson KG, Trinh TT, Yatich N, Nyongesa-Malava E, Kiptinness C, Richardson BA, John-Stewart GC, De Vuyst H, Sakr SR, Mugo NR, Chung MH. Increased Cervical Human Immunodeficiency Virus (HIV) RNA Shedding Among HIV-Infected Women Randomized to Loop Electrosurgical Excision Procedure Compared to Cryotherapy for Cervical Intraepithelial Neoplasia 2/3. Clin Infect Dis. 2018 May 17;66(11):1778-1784. doi: 10.1093/cid/cix1096.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2011
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: February 16, 2011
• First Submitted That Met QC Criteria: February 16, 2011
• First Posted (Estimate): February 17, 2011

Study Record Updates

• Last Update Posted (Actual): November 12, 2019
• Last Update Submitted That Met QC Criteria: October 19, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms; Carcinoma in Situ; Cervical Intraepithelial Neoplasia
• Other Study ID Numbers: 35995-J; KE.09.0238 (Other Identifier: Kenya Ethical Review Committee)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No