HPV Vaccination Prior to Loop Electroexcision Procedure does not Prevent Recurrent Cervical High Grade Squamous Intraepithelial Lesions in Women Living with HIV: a Randomized, Double-blind, Placebo-controlled Trial.
BACKGROUND: Women living with HIV, especially in sub-Saharan Africa, are at high risk for cervical high-grade squamous intraepithelial lesions (HSIL) and cervical cancer. These women have high HSIL recurrence rates after loop electroexcision procedure (LEEP). Retrospective studies suggest that HPV vaccination improves response to treatment of cervical HSIL. METHODS: We performed a double-blind, randomized clinical trial enrolling 180 women living with HIV in Johannesburg, South Africa diagnosed with cervical HSIL by colposcopic biopsy. Women received quadrivalent HPV vaccine or placebo (1:1) at entry, week 4, and week 26. LEEP was performed at week 4. Colposcopic directed biopsies and cervical cytology were performed at week 26 and 52. The primary endpoint, cervical HSIL by histology or cytology at either week 26 or 52, was compared between arms using Chi-square analysis. RESULTS: Participant characteristics included median age 39 years, median CD4 489 cells/mm3, and 94% had HIV suppression. 174 women completed the vaccine/placebo series and had evaluable results at week 26 or 52. The proportion experiencing the primary endpoint was similar in the vaccine and placebo groups, 53% vs. 45% (RR 1.16, 95% CI .87-1.6, P=.29). HSIL recurrence was associated with a LEEP biopsy result of HSIL and detection of HSIL at the margins of LEEP sample. CONCLUSION: This study did not support HPV vaccination to prevent recurrent HSIL after LEEP in women living with HIV. Recurrent HSIL was high despite virologic suppression. Improved treatments are needed for HSIL to reduce the burden of cervical cancer among women living with HIV.