Cervical screening and treatment using visual inspection with acetic acid (VIA) and cryotherapy (screen-and-treat) is often implemented in resource-limited settings with high HIV-1 endemicity; however, cryotherapy may be less effective than loop electrosurgical excisional procedure (LEEP) among HIV-infected women. We randomized 400 HIV-infected women to cryotherapy or LEEP and examined the recurrence of cervical disease over a 2-year follow-up.
From June 2011 to July 2014, HIV-infected women enrolled at the Coptic Hope Center for Infectious Diseases in Nairobi, Kenya underwent cervical screening with Pap smear and confirmatory biopsy. Four hundred women with cervical intraepithelial neoplasia (CIN)2/3 or carcinoma in situ (CIS) disease were randomized 1:1 to receive cryotherapy or LEEP, and were followed every 6 months with a Pap smear for 2 years. Recurrence was defined as high grade squamous intraepithelial lesions (HSIL) or greater on cytology, and outcomes were compared between arms using Chi-square tests and Cox proportional hazards regression.
Sociodemographic and biological factors were balanced between arms. Median age was 37 years [interquartile range (IQR): 31-43], most women were on ART (89%) at the time of intervention, and median CD4 was 380 cells/μl (IQR: 215-524). Among women randomized to cryotherapy: 71 (35.5%) had CIN2 at baseline, 107 (53.5%) CIN3, 11 (5.5%) CIS, and 11 (5.5%) no dysplasia/CIN1. In the LEEP arm: 59 women (29.5%) had CIN2, 116 (58%) CIN3, 10 (5%) CIS, and 15 (7.5%) no dysplasia/CIN1. Median follow-up was 2.1 years in both arms and 341 (85%) women completed all 4 follow-up visits. At 12-months, more women treated with cryotherapy experienced recurrent HSIL than those who underwent LEEP (27% vs 18%; P=0.031). At 24 months, HSIL increased in both arms and remained significantly higher in the cryotherapy arm (37% vs 26%; P=0.018). Overall, the rate of recurrence of HSIL+ was 21.1 per 100 woman-years after cryotherapy and 14.0 per 100 woman-years after LEEP. Women treated with cryotherapy were 52% more likely to experience recurrence (hazard ratio (HR): 1.52, 95% confidence interval [CI]: 1.07-2.17; P=0.020) compared to LEEP.
Treatment with cryotherapy was associated with significantly higher risk of recurrent pre-cancerous cervical disease among HIV-infected women compared to LEEP. In high HIV-burden settings, a screen-and-treat approach coupled with HIV testing and referral for LEEP may be more effective than cryotherapy alone.