Dataset Information

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.

ABSTRACT:

Importance

The 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.

Objective

To evaluate whether cryotherapy or LEEP is a more effective treatment for high-grade cervical lesions among women with HIV.

Design, setting, and participants

Single-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.

Interventions

Women 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 measures

The primary outcome was disease recurrence, defined as CIN grade 2 or higher on cervical biopsy, during the 24-month follow-up period.

Results

Among 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 relevance

In 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 registration

ClinicalTrials.gov Identifier: NCT01298596.

SUBMITTER: Greene SA

PROVIDER: S-EPMC6806442 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAs LEEP (loop electrosurgical excision procedure) is being increasingly used for the diagnosis and treatment of uterine cervical intraepithelial neoplasia, surgical smoke during LEEP has become an inevitable health issue. Therefore, in this study, exposure to the chemical substances in surgical smoke produced during LEEP was assessed.MethodsSmoke samples from patients with high-grade cervical intraepithelial neoplasia undergoing LEEP were collected by smoke-absorbing devices situated 1 m away from the operating table and near the nose of the operator during LEEP. Each plume sample was collected after 5 patients underwent LEEP, requiring 5 min for smoke collection for each patient. The chemicals of exposure to surgical smoke were assessed, and the hazard classes of these chemical components were evaluated by the International Agency for Research on Cancer.ResultsQualitative analysis of the smoke produced during LEEP revealed a variety of potentially toxic chemicals under standard detection, such as benzene, toluene, xylene, ethylbenzene, styrene, butyl acetate, acrylonitrile, 1,2-dichloroethane, phenol, chlorine, cyanide, hydrogen cyanide and carbon monoxide. Additionally, the average concentration of carbon dioxide was 0.098 ± 0.015% during surgery and was higher than that before surgery (0.072 ± 0.007%, P < 0.001), and the concentration of formaldehyde was significantly higher during surgery (0.023 ± 0.009 mg/m3, P < 0.05) than before surgery (0.012 ± 0.001 mg/m3, P < 0.05).ConclusionsMost of the detected chemical concentrations in smoke generated during LEEP were below the exposure limits when local exhaust ventilation procedures were efficiently used. However, the concentrations of carbon dioxide and formaldehyde found in smoke were significantly higher after surgery. Wearing a high-filtration mask and using evacuation devices routinely and consistently when performing LEEP are recommended to protect perioperative personnel.

Project description:ImportancePersistence of cervical high-risk human papillomavirus (hrHPV) after treatment for cervical intraepithelial neoplasia grade 2 or higher (CIN2+) has not been compared between cryotherapy and loop electrosurgical excision procedure (LEEP) among HIV-positive women.ObjectiveTo evaluate whether cryotherapy or LEEP is more effective at clearing hrHPV and whether persistent hrHPV is associated with CIN2+ recurrence among HIV-positive women.Design, setting, and participantsThis is a secondary analysis of a randomized clinical trial conducted among women with HIV, hrHPV, and CIN2+ in Nairobi, Kenya. From June 2011 to September 2016, 354 HIV-positive women with CIN2+ disease had hrHPV cervical samples collected before and after treatment with cryotherapy or LEEP. Data were analyzed from September 2018 to January 2021.InterventionsWomen were randomized 1:1 to receive cryotherapy or LEEP and were followed up every 6 months for 24 months with hrHPV cervical swab and Papanicolaou test with confirmatory biopsy.Main outcomes and measuresThe main outcomes of this analysis were hrHPV positivity defined as having 1 of 12 hrHPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and disease recurrence defined as CIN grade 2 or higher as determined with cervical biopsy.ResultsA total of 354 HIV-positive women with CIN2+ were included in the study; mean (SD) age was 37 (8) years in the cryotherapy arm and 38 (9) years in the LEEP arm. Baseline hrHPV prevalence was 90% (160 of 177) in the cryotherapy arm and 94% (166 of 177) in the LEEP arm (P = .24), and the most common hrHPV types detected were 16 (87 of 326 [27%]), 58 (87 of 326 [27%]), 35 (86 of 326 [26%]), 52 (66 of 326 [20%]), and 18 (56 of 325 [17%]). Over 24 months, clearance of hrHPV was significantly higher among those who underwent LEEP compared with cryotherapy (hazard ratio, 1.40; 95% CI, 1.03-1.90; P = .03). In multivariable analysis, hrHPV type-specific persistence at 12-month follow-up was significantly associated with CIN2+ recurrence from 12 months to 24 months (adjusted hazard ratio, 4.70; 95% CI, 2.47-8.95; P < .001). Performance of hrHPV testing at 12 months for recurrent CIN2+ was 93% sensitivity, 46% specificity, 38% positive predictive value, and 95% negative predictive value.Conclusions and relevanceIn this secondary analysis of a randomized clinical trial, HIV-positive women who received LEEP were more likely to clear hrHPV infection compared with those undergoing cryotherapy, reinforcing the efficacy of LEEP in this population. Persistent hrHPV was significantly associated with recurrent CIN2+, suggesting that LEEP's benefits may be related in part to its ability to clear hrHPV infection. Screening for hrHPV infection after treatment among HIV-positive women may be used to rule out recurrent CIN disease given its high sensitivity and negative predictive value.Trial registrationClinicalTrials.gov Identifier: NCT01298596.

Project description:It has been reported that chitosan has a hemostatic effect and an antibiotic activity. This study aimed to evaluate the efficacy and feasibility of using a chitosan tampon (Hemoblock-Tampon) in preventing hemorrhage and enhancing wound healing after the loop electrosurgical excision procedure (LEEP).This single-blind, prospective, randomized study included 62 consecutive patients who underwent LEEP for cervical intraepithelial neoplasia. A chitosan tampon (31 patients; treatment group), or a general tampon (31 patients; control group) was applied to the uterine cervix immediately after LEEP. One patient in the treatment group declined to participate in this study. Thus, 30 patients in the treatment group and 31 patients in the control group completed this study. For objective analysis of hemorrhage in the postoperative 2 weeks, the amounts of bleeding were checked daily with a pictorial blood assessment chart. We evaluated vaginal discharge, abdominal pain, and impairment in daily living during the postoperative 2 weeks using 5 visual analogue scale questionnaires.The bleeding count was significantly lower in the treatment group than in the control group (21.37 ± 16.86 vs. 40.52 ± 16.55, p = 0.0014). The sum of the scores of the 5 questionnaires was significantly lower in the treatment group than in the control group (6.53 ± 2.84 vs. 8.59 ± 2.88, p = 0.0079). The incidence of vaginal discharge was significantly lower in the treatment group than in the control group (20.0% vs. 48.4%, p = 0.0207). According to logistic regression, only the use of chitosan tampon reduced the risk of moderate to severe vaginal bleeding 2 weeks after surgery (Odd ratio, 0.213; 95% confidence interval, 0.06-0.76; p = 0.0172). Complete healing of the uterine cervix occurred in 86.7% of patients in the treatment group and in 61.3% of patients in the control group at 4 weeks after surgery (p = 0.0255).The use of chitosan tampons can reduce hemorrhage, vaginal discharge, abdominal pain, and impairment of daily living after LEEP. Moreover, chitosan tampon may help enhance wound healing.

Project description:BackgroundThe complications inherent to conization include vaginal bleeding, cervical stenosis, amenorrhea, dysmenorrhea, and deep dyspareunia. Cervical stenosis is the most important complication due to the clinical repercussions. Studies show rates of cervical stenosis ranging from 1.3 to 19% after the Loop Electrosurgical Excision Procedure (LEEP).ObjectiveOur primary outcome was to compare the role of a new endocervical device to prevent cervical stenosis after LEEP in patients with high-grade squamous intraepithelial lesions (HSILs).MethodsA randomized clinical trial was performed including phases II and III for evaluation of a new device for cervical stenosis prevention. In Phase II, we included 25 patients who underwent LEEP and placement of the device to assess its toxicity and efficacy. In phase III, we compared two groups (with and without the use of an anti-stenosis device) to evaluate its efficacy and safety.ResultsFrom August 2015 to June 2018, 265 participants were randomized (Phase II: 25, Phase III: 120 with DUDA and 120 without DUDA). The toxicity during phase II was observed in only one patient (4%) with pain grade > 7. There were 7 cases of toxicity during Phase III, 2 in the DUDA group (1.8%), and 5 in the No DUDA group (4.5%). The complications rate was numerically higher in the No DUDA group (2.5x higher) than the DUDA group, but this difference did not reach statistical significance (p = 0.52). The rate of cervical stenosis in DUDA group was (4-7,3%), and in No DUDA group was (4.3-5.8%) (p = 0.5). We did not find a significant difference when comparing the evolution at 3, 6, and 12 months in terms of cervical patency and visualization of the squamocolumnar junction (SCJ) during colposcopy. The DUDA group exhibited 15% to 19% nonvisualization of the SCJ, whereas that rate ranged from 10 to 12% in the No DUDA group.ConclusionsThe rate of cervical stenosis was not different comparing the use of a new device, specifically produced to prevent cervical stenosis, compared to no use after LEEP procedure. This clinical trial opens up space for a discussion of the utility of using cervical stenosis devices after LEEP. Perhaps in another type of conization it can be evaluated to avoid cervical stenosis.

Project description:IntroductionAdenocarcinoma in situ (AIS) of the uterine cervix is the precursor to invasive endocervical adenocarcinoma. An excisional biopsy such as a cold knife cone biopsy (CKC) should be performed to exclude invasive adenocarcinoma. Loop electrosurgical excision procedure (LEEP) is an alternative modality to CKC but is controversial in AIS. There is a perception that there is a greater likelihood of incomplete excision of AIS with LEEP because the depth of excised tissue tends to be smaller and the tissue margins may show thermal artefact which can interfere with pathology assessment. In the USA, guidelines recommend that any treatment modality can be used to excise AIS, provided that the specimen remains intact with interpretable margins. However, there are no high-quality studies comparing LEEP with CKC and well-designed prospective studies are needed. If such a study were to show that LEEP was non-inferior to CKC for the outcomes of post-treatment persistence, recurrence and adenocarcinoma, LEEP could be recommended as an appropriate treatment option for AIS in selected patients. This would benefit women because, unlike CKC, LEEP does not require general anaesthesia and may be associated with reduced morbidity.Methods and analysisThe proposed exploratory study is a parallel group trial with an allocation ratio of 2:1 in favour of the intervention (LEEP: CKC). Participants are women aged ≥18 to ≤45 years diagnosed with AIS on cervical screening and/or colposcopically directed biopsy in Australia and New Zealand, who are to receive excisional treatment in a tertiary level centre.Ethics and disseminationEthical approval for the study has been granted by the St John of God Healthcare Human Research Ethics Committee (reference number #1137). Results from the study will be presented at conferences and published in a peer-reviewed scientific journal.RegistrationANZCTR registration number ACTRN12617000132347 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372173&isReview=true.