Loop Electrosurgical Excision Procedure for HIV+ Women More Likely to Clear High-Risk HPV Infection vs Cryotherapy for CIN

A secondary analysis of a clinical trial indicated that women who were human immunodeficiency virus–positive and underwent loop electrosurgical excision procedure for cervical intraepithelial neoplasia had an increased likelihood of clearing high-risk human papillomavirus than women who underwent cryotherapy.

Women who were human immunodeficiency virus–positive and received loop electrosurgical excision procedure (LEEP) for grade 2 cervical intraepithelial neoplasia (CIN2) were more likely to clear high-risk human papillomavirus (hrHPV) than women who underwent cryotherapy over a 24-month period (HR, 1.40; 95% CI, 1.03-1.90; P = .03), according to results from the secondary analysis of a study (NCT01298596) published in JAMA Oncology.

At baseline, overall prevalence of any hrHPV was 92%, with specific hrHPV prevalence of 90% in the cryotherapy arm and 94% in the LEEP arm (P = .24). The most common types of hrHPV detected among patients were 16 (27%), 58 (27%), 35 (26%), 52 (20%), and 18 (17%).

“This secondary analysis of a [randomized clinical trial] supports the clinical benefits of LEEP over cryotherapy if this method is available and accessible in low- and middle-income countries,” the investigators wrote. “Testing for hrHPV after cervical treatment is useful in ruling out recurrent cervical disease among women living with HIV and could be administered as early as 6 months after treatment.”

Women living with HIV were recruited from the Coptic Hope Center for Infectious Diseases in Nairobi, Kenya, and provided informed written consent to participate on the study. Eligibility criteria required that patients be aged 18 years or older, HIV positive, sexually active, not pregnant, and have an intact cervix.

According to World Health Organization International Agency for Research on Cancer categorization, 12 types of HPV were considered high risk, including type 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59 disease.

The main outcomes of this secondary analysis were hrHPV positivity and disease recurrence, which was defined as CIN2 or higher.

HIV-positive women were enrolled on the trial between June 2011 and September 2016, of whom 354 were confirmed to be CIN2-positive on colposcopy-directed biopsy. The population was divided evenly, with 177 women each receiving cryotherapy or LEEP treatment. Demographics between the cryotherapy and LEEP groups were similar, with most patients having a monthly household income of less than $150 per month (62% vs 64%; P = .79) and at least 2 years of antiretroviral treatment (ART) the time of enrollment (51% vs 57%; P = .20). Additionally, 29% of patients in the cryotherapy arm and 27% of patients in the LEEP arm were similarly immunocompromised, with CD4 counts less than 250 cells/mm3 (P = .75)

After 12 months of undergoing treatment, type-specific baseline hrHPV persistence was higher for women who underwent cryotherapy (61%) compared with those who underwent LEEP (49%; P = .04). Moreover, persistence was higher for the cryotherapy arm compared with LEEP treatment arm among those with hrHPV type 16 (69% vs 48%; P = .046) and type 51 disease (44% vs 12%; P = .04).

A notable number of women with type-specific hrHPV persistence at 12 months were found to have recurrent CIN2 positivity during the follow up period of 2 years. hrHPV persistence and recurrent CIN2 positivity was observed in patients who had a single type-specific hrHPV detection at enrollment (61%), hrHPV types 16 and/or 18 (48%), any type-specific hrHPV (42%), multiple type- specific hrHPV (32%).

Type-specific hrHPV persistence maintained a high and statistically significant association with CIN2-positive recurrence in multivariable analyses including treatment intervention and CD4 count (aHR, 4.70; 95% CI, 2.47-8.95; P <.001).

“Further study is needed to determine the cost-effectiveness of LEEP and the long-term implications of hrHPV persistence after treatment on cervical cancer and mortality among women living with HIV,” the investigators concluded.


Chung MH, De Vuyst H, Greene SA, et al. Human papillomavirus persistence and association with recurrent cervical intraepithelial neoplasia after cryotherapy vs loop electrosurgical excision procedure among HIV-positive women: a secondary analysis of a randomized clinical trial. JAMA Oncol. 2021;7(10):1514-1520. doi:10.1001/jamaoncol.2021.2683