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A randomized clinical trial comparing cervical dysplasia treatment with cryotherapy vs loop electrosurgical excision procedure in HIV-seropositive women from Johannesburg, South Africa

Published:March 30, 2017DOI:https://doi.org/10.1016/j.ajog.2017.03.022

      Background

      Mortality associated with cervical cancer is a public health concern for women, particularly in HIV–seropositive women in resource-limited countries. HIV-seropositive women are at a higher risk of high-grade cervical precancer, which can eventually progress to invasive carcinoma as compared to HIV-seronegative women. It is imperative to identify effective treatment methods for high-grade cervical precursors among HIV-seropositive women.

      Objective

      Randomized controlled trial data are needed comparing cryotherapy vs loop electrosurgical excision procedure treatment efficacy in HIV-seropositive women. Our primary aim was to compare the difference in the efficacy of loop electrosurgical excision procedure vs cryotherapy for the treatment of high-grade cervical intraepithelial neoplasia (grade ≥2) among HIV-seropositive women by conducting a randomized clinical trial.

      Study Design

      HIV-seropositive women (n = 166) aged 18-65 years with histology-proven cervical intraepithelial neoplasia grade ≥2 were randomized (1:1) to cryotherapy or loop electrosurgical excision procedure treatment at a government hospital in Johannesburg. Treatment efficacy was compared using 6- and 12-month cumulative incidence posttreatment of: (1) cervical intraepithelial neoplasia grade ≥2; (2) secondary endpoints of histologic cervical intraepithelial neoplasia grade ≥3 and grade ≥1; and (3) high-grade and low-grade cervical cytology. The study was registered (ClinicalTrials.gov NCT01723956).

      Results

      From January 2010 through August 2014, 166 participants were randomized (86 loop electrosurgical excision procedure; 80 cryotherapy). Cumulative cervical intraepithelial neoplasia grade ≥2 incidence was higher for cryotherapy (24.3%; 95% confidence interval, 16.1–35.8) than loop electrosurgical excision procedure at 6 months (10.8%; 95% confidence interval, 5.7–19.8) (P = .02), although by 12 months, the difference was not significant (27.2%; 95% confidence interval, 18.5–38.9 vs 18.5%; 95% confidence interval, 11.6–28.8, P = .21). Cumulative cervical intraepithelial neoplasia grade ≥1 incidence for cryotherapy (89.2%; 95% confidence interval, 80.9–94.9) did not differ from loop electrosurgical excision procedure (78.3%; 95% confidence interval, 68.9–86.4) at 6 months (P = .06); cumulative cervical intraepithelial neoplasia grade ≥1 incidence by 12 months was higher for cryotherapy (98.5%; 95% confidence interval, 92.7–99.8) than loop electrosurgical excision procedure (89.8%; 95% confidence interval, 82.1–95.2) (P = .02). Cumulative high-grade cytology incidence was higher for cryotherapy (41.9%) than loop electrosurgical excision procedure at 6 months (18.1%, P < .01) and 12 months (44.8% vs 19.4%, P < .001). Cumulative incidence of low-grade cytology or greater in cryotherapy (90.5%) did not differ from loop electrosurgical excision procedure at 6 months (80.7%, P = .08); by 12 months, cumulative incidence of low-grade cytology or greater was higher in cryotherapy (100%) than loop electrosurgical excision procedure (94.8%, P = .03). No serious adverse effects were recorded.

      Conclusion

      Although rates of cumulative cervical intraepithelial neoplasia grade ≥2 were lower after loop electrosurgical excision procedure than cryotherapy treatment at 6 months, both treatments appeared effective in reducing cervical intraepithelial neoplasia grade ≥2 by >70% by 12 months. The difference in cumulative cervical intraepithelial neoplasia grade ≥2 incidence between the 2 treatment methods by 12 months was not statistically significant. Relatively high cervical intraepithelial neoplasia grade ≥2 recurrence rates, indicating treatment failure, were observed in both treatment arms by 12 months. A different treatment protocol should be considered to optimally treat cervical intraepithelial neoplasia grade ≥2 in HIV-seropositive women.

      Key words

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      Linked Article

      • Recurrence of CIN 2 and 3 after treatment in HIV positive patients
        American Journal of Obstetrics & GynecologyVol. 219Issue 2
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          A randomized controlled trial of 166 HIV-positive patients comparing treatment for cervical intraepithelial neoplasia (CIN) 2 and 3 by loop electrosurgical excision (LEEP) (n = 86) and cryotherapy (n = 80) in a tertiary government hospital in South Africa, published in the August edition of this journal,1 highlights the high recurrence rates after treatment.
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