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

Key PointsQuestionAmong women with HIV and high-grade cervical lesions, what is the effect of cryotherapy vs loop electrosurgical excision procedure (LEEP) on cervical disease recurrence? FindingsIn this randomized clinical trial that included 400 women in Kenya with HIV and high-grade cervical lesions, treatment with cryotherapy, compared with LEEP, led to a significantly higher rate of cervical intraepithelial neoplasia grade 2 or 3 recurrence (30% vs 19%) over 24 months. MeaningThese findings support the effectiveness of LEEP for treatment of cervical precancer in women with HIV, although cost-effectiveness analysis is necessary to understand whether the additional benefit of LEEP represents an efficient use of additional resources. ImportanceThe World Health Organization recommends cryotherapy or loop electrosurgical excision procedure (LEEP) for histologically confirmed cervical intraepithelial neoplasia (CIN) grade 2 or higher regardless of HIV status. Cryotherapy is more feasible in resource-limited settings but may be less effective for women living with HIV. ObjectiveTo evaluate whether cryotherapy or LEEP is a more effective treatment for high-grade cervical lesions among women with HIV. Design, Setting, and ParticipantsSingle-center randomized trial conducted among women with HIV and CIN grade 2 or 3. From June 2011 to September 2016, women with HIV in Kenya underwent cervical screening with Papanicolaou testing and confirmatory biopsy. The final date on which a study procedure was administered was September 7, 2016. InterventionsWomen with HIV infection and CIN grade 2 or 3 were randomized 1:1 to receive cryotherapy (n=200) or LEEP (n=200) and were followed up every 6 months for 24 months with a Papanicolaou test and confirmatory biopsy. Main Outcome and MeasuresThe primary outcome was disease recurrence, defined as CIN grade 2 or higher on cervical biopsy, during the 24-month follow-up period. ResultsAmong 400 women who were randomized (median age, 37.4 [interquartile range, 31.9-43.8] years), 339 (85%) completed the trial. Over 2 years, 60 women (30%) randomized to cryotherapy had recurrent CIN grade 2 or higher vs 37 (19%) in the LEEP group (relative risk, 1.71 [95% CI, 1.12-2.65]; risk difference, 7.9% [95% CI, 1.9%-14.0%]; P=.01). Adverse events occurred in 40 women (45 events, including change in pathology and death due to other causes) in the cryotherapy group and in 30 women (38 events, including change in pathology and unrelated gynecological complications) in the LEEP group. Conclusions and RelevanceIn this single-center study of women with HIV infection and CIN grade 2 or 3, treatment with LEEP compared with cryotherapy resulted in a significantly lower rate of cervical neoplasia recurrence over 24 months. Cost-effectiveness analysis is necessary to determine whether the additional benefit of LEEP represents an efficient use of the additional resources that would be required. Trial RegistrationClinicalTrials.gov Identifier: NCT01298596 This randomized clinical trial compares the effect of cryotherapy vs loop electrosurgical excision procedure (LEEP) on disease recurrence (cervical intraepithelial neoplasia [CIN] grade 2 or higher or invasive cervical cancer) in women with HIV and CIN grade 2 or 3.