Cervical intraepithelial neoplasia in migrant women living with HIV

Abstract: The aim of this thesis was to study high-grade cervical intraepithelial neoplasia (CIN) in women living with HIV (WLWH) in Sweden compared with HIV-negative women (HNW) of the same region of birth. In Paper I we assessed the cumulative incidence (CuI) and hazard ratio (HR) of CIN3, adenocarcinoma, and invasive cervical cancer (CIN3+) in a cohort of WLWH (n = 893) and HNW (n = 205 842) by linking the Swedish national HIV registry (InfCare HIV) with the Swedish Population Registry (SPR) and the Swedish National Cervical Screening Registry (NKCx). The CuI of CIN3+ was 13.1% (95% CI 8.9-17.2) and 2.1% (95% CI 2.0-2.2) for WLWH and HNW, respectively. WLWH had more than eight times higher risk of CIN3+ than HNW (HR 8.8: 95% CI 6.9–11.3), increasing with the level of immunosuppression. The highest risk was seen in WLWH born in the East region, dominated by Thai women. In Paper II we analysed if the prevalence of undiagnosed HIV in women diagnosed with CIN2+ (n = 62 874) in the counties of Stockholm and Gothenburg, Sweden, would reach the threshold of 0.1%, which has been suggested cost-effective for HIV-testing. The proportion of undiagnosed HIV was calculated by linking NKCx with InfCare HIV and did not exceed 0.1% in all women, indicating that HIV-testing all women with CIN2+ in Sweden may not be cost-effective. However the proportion of undiagnosed HIV exceeded 0.1% among migrant women diagnosed with CIN2+ suggesting that HIVtesting should routinely be performed in this population. In Paper III we assessed outcome after treatment of CIN2+ in 140 WLWH and 284 HNW, matched for country of birth, identified by linking NKCx with InfCare HIV and SPR. WLWH were three times more likely to have treatment failure (odds ratio (OR) 3.7 [95% CI 2.0-6.8]) and five times more likely to recur (hazard ratio 5.0: 95% CI 2.1-11.6) than HNW. Suppressive (HIV-RNA<50 copies/mL) antiretroviral therapy (ART) at time of treatment of CIN2+ was associated with reduced odds ratio of treatment failure (OR 0.3: 95% CI 0.1-0.8). In Paper IV we studied whether HPV genotypes in women with CIN2+, identified in paper III, differed depending on their HIV status. Cervical tissue blocks of included women were retrieved from bio banks and HPV type was identified using modified general primer PCR and Luminex genotyping. WLWH were less likely to be infected with HPV 16 (prevalence ratio [PR] 0.6: 95% CI 0.35-0.97), and more likely to be infected with multiple high-risk (HR) HPV (PR 2.1, 95% CI 1.17-3.79). Only 25% of WLWH vs. 47% of HNW had HR HPV types that are covered by the bivalent and quadrivalent HPV vaccines (HPV 16 and/or 18) (PR 0.6: 95% CI 0.38-0.97). In summary, my thesis showed that WLWH in Sweden are at higher risk of developing CIN3+, have poorer outcome after treatment of CIN2+, and less proportion of HPV 16 than HNW. We also found level of immunosuppression and, for the first time, suppressive ART to be associated with effective treatment of CIN2+. We recommend migrants diagnosed with CIN2+ to be HIV-tested. Early HIV diagnosis, access and adherence to ART, HPV vaccination of young people living with HIV and those at high-risk of HIV-infection, and finally access and adherence to cervical cancer screening are all crucial to minimize the incidence of CIN2+ and its progression to ICC in WLWH.