title: A randomized clinical trial comparing cervical dysplasia treatment with cryotherapy vs loop electrosurgical excision procedure in HIV-seropositive women from Johannesburg, South Africa.
abstract: 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.
  
  
  
  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.
  
  
  
  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.govNCT01723956).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC. Electronic address: jennifers@unc.edu.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Smith
authors.affiliation: Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC.
authors.forename: Busola
authors.initials: B
authors.lastname: Sanusi
authors.affiliation: Department of Internal Medicine, Clinical HIV Research Unit, Faculty of Health Science Center, University of Witwatersrand, Johannesburg, South Africa.
authors.forename: Avril
authors.initials: A
authors.lastname: Swarts
authors.affiliation: Right to Care, Johannesburg, South Africa.
authors.forename: Mark
authors.initials: M
authors.lastname: Faesen
authors.affiliation: Department of Obstetrics and Gynecology, Rahima Moosa Mother and Child Hospital, University of Witwatersrand, Johannesburg, South Africa; Right to Care, Johannesburg, South Africa.
authors.forename: Simon
authors.initials: S
authors.lastname: Levin
authors.affiliation: Right to Care, Johannesburg, South Africa.
authors.forename: Bridgette
authors.initials: B
authors.lastname: Goeieman
authors.affiliation: Right to Care, Johannesburg, South Africa.
authors.forename: Sibongile
authors.initials: S
authors.lastname: Ramotshela
authors.affiliation: Right to Care, Johannesburg, South Africa.
authors.forename: Ntombiyenkosi
authors.initials: N
authors.lastname: Rakhombe
authors.affiliation: Department of Clinical Laboratory Sciences, Institute of Infectious Disease and Division of Medical Virology, University of Cape Town, Cape Town, South Africa; National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Williamson
authors.affiliation: Department of Anatomical Pathology, Cytology Unit, Faculty of Health Science, University of Witwatersrand, Johannesburg, South Africa; National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Pam
authors.initials: P
authors.lastname: Michelow
authors.affiliation: Department of Anatomical Pathology, Cytology Unit, Faculty of Health Science, University of Witwatersrand, Johannesburg, South Africa; National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Tanvier
authors.initials: T
authors.lastname: Omar
authors.affiliation: Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hudgens
authors.affiliation: Department of Internal Medicine, Clinical HIV Research Unit, Faculty of Health Science Center, University of Witwatersrand, Johannesburg, South Africa; Right to Care, Johannesburg, South Africa.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Firnhaber
mesh_terms: D017679:Cryotherapy; D004598:Electrosurgery; D005260:Female; D006679:HIV Seropositivity / Q000150:complications*; D006801:Humans; D060787:Neoplasm Grading; D013019:South Africa; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000150:complications* / Q000473:pathology / Q000628:therapy*; D002578:Uterine Cervical Dysplasia / Q000150:complications* / Q000473:pathology / Q000628:therapy*
keywords: HIV; cervical cancer; cryotherapy; loop electrosurgical excision procedure; randomized clinical trial; treatment