Long-term risk of recurrence of pre-cancerous cervical lesions among women living with HIV in Kenya

Women living with HIV (WLHIV) have a six-fold increased risk of developing cervical cancer compared to HIV-uninfected women. Despite this, limited data exists on the recurrence of precancerous cervical lesions among WLHIV following treatment with loop electrical excision procedure (LEEP) or cryotherapy. We sought to determine the long-term risk of recurrence of cervical intraepithelial neoplasia grade 2 or higher (CIN 2+) and associated risk factors among WLHIV with prior treatment for cervical disease. Methods We conducted a long-term follow-up study of WLHIV and CIN grade 2 or 3 previously randomized to LEEP or cryotherapy in Nairobi, Kenya between 2011 and 2013 Former trial participants were recontacted between January and August 2023 for cervical cancer screening using Papanicolaou (PAP) test and colposcopy-directed biopsy to determine presence of precancerous cervical lesions in the ≥9 years since initial treatment. Women with PAP results of low grade squamous intraepithelial lesions (LSIL), high grade squamous intraepithelial lesions (HSIL) or atypical squamous cells with the inability to exclude HSIL (ASC-H) underwent colposcopy-directed biopsy. Primary and secondary outcomes were 1) recurrence of CIN 2+ (CIN 2, CIN 3, Carcinoma in-situ or invasive cancer) as determined by colposcopy-directed biopsy, measured ≥9 years after initial treatment, and 2) recurrence of HSIL+ (HSIL, ASC-H or invasive cancer) on PAP smear, measured ≥9 years after initial treatment, respectively. Log-binomial regression was used to estimate the relative risk of CIN 2+ and HSIL+ recurrence by treatment arm. Results Of the 400 former trial participants, 286 (71.5%) were recontacted of which 197 (68.9%) agreed to participate in this follow-up study. Five (4.7%) of 107 participants in the cryotherapy arm and 3 (3.3%) of 90 in the LEEP arm had recurrent CIN 2+ in this follow-up study. In addition, 10 (9.3%) participants in the cryotherapy arm and 4 (4.4%) in the LEEP arm had recurrence of HSIL+ in the ≥9 years since initial treatment. There was no difference in long-term risk of recurrence of CIN2+ and HSIL+ between treatment arms (RR=1.40, 95% Confidence Interval (95% CI), 0.34-5.71, p=0.64; and RR=2.10 95% CI, 0.68-6.48, p=0.18, respectively). Longer duration of antiretroviral therapy (≥10 years) was not significantly associated with recurrence of CIN2+ or HSIL2+. However, those with a nadir CD4 count of ≥500 cells/mm3 were 6 times more likely to have a recurrence compared to those whose CD4 count of less than 500 cells/mm3, a finding we postulate to be spurious (RR = 6.46 95% CI: 1.72, 24.26, p=0.01) Conclusions The long-term risk of recurrence of pre-cancerous cervical lesions among WLHIV was low.