Efficacy and safety of therapeutic HPV vaccines to treat CIN 2/CIN 3 lesions: a systematic review and meta-analysis of phase II/III clinical trials.

OBJECTIVES: We aim to assess the efficacy and safety of therapeutic human papillomavirus (HPV) vaccines to treat cervical intraepithelial neoplasia of grade 2 or 3 (CIN 2/3). DESIGN: Systematic review and meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. DATA SOURCES: PubMed, Embase, Web of Science, Global Index Medicus and CENTRAL Cochrane were searched up to 31 January 2022. ELIGIBILITY CRITERIA: Phase II/III randomised controlled trials (RCTs) and single-arm studies reporting the efficacy of therapeutic vaccines to achieve regression of CIN 2/3 lesions were included. Studies evaluating only safety and side effects of the vaccine were excluded. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and evaluated study quality. A random-effect model was used to pool the proportions of regression and/or HPV clearance. RESULTS: 12 trials met the inclusion criteria. Out of 734 women (all studies considered) receiving therapeutic HPV vaccine for CIN 2/3, 414 regressed to normal/CIN 1 with an overall proportion of regression of 0.54 (95% CI 0.39 to 0.69) for vaccinated group; 166 women (from five RCTs) receiving placebo only achieving a pooled normal/CIN 1 regression of 0.27 (95% CI 0.20 to 0.34). When including only the five two-arm studies, the regression proportion for the 410 vaccine group participants was higher than that of the 166 control group participants (relative risk (RR) 1.52; 95% CI 1.14 to 2.04). The pooled proportion of high-risk human papillomavirus (hrHPV) clearance was 0.42 (95% CI 0.32 to 0.52) in the vaccine group (six studies with a total of 357 participants) and 0.17 (95% CI 0.11 to 0.26) in the control group (three RCTs with a total of 104 participants). Based on these three RCTs, the hrHPV clearance was significantly higher in the vaccinated group (250 participants) compared with the control group (RR 2.03; 95% CI 1.30 to 3.16). Similar results were found regarding HPV 16/18 clearance. No significant unsolicited adverse events have been consistently reported. CONCLUSIONS: The efficacy of the therapeutic vaccines in the treatment of CIN 2/3 was modest. Implementation issues such as feasibility, acceptability, adoption and cost-effectiveness need to be further studied. PROSPERO REGISTRATION NUMBER: CRD42022307418.

Burden of Kaposi sarcoma according to HIV status: A systematic review and global analysis.

In 2020, over 34 000 cases of Kaposi sarcoma (KS) were estimated globally, all attributable to KS herpesvirus (KSHV). Prior to the HIV epidemic, KS already existed in KSHV endemic regions, notably in sub-Saharan Africa (SSA). The HIV epidemic has vastly increased the KS burden. We developed a methodology to provide global estimates of KS burden according to HIV status. A systematic review identified studies reporting HIV prevalence in consecutive KS series. Pooled estimates of HIV prevalence, by country or UN subregion, were used to calculate population-attributable fraction (PAF) and these were applied to IARC's GLOBOCAN 2020 to estimate burden and incidence of HIV-attributable and non-HIV-attributable KS. We identified 55 eligible studies, reporting HIV prevalence ranging from ≤5% to ≥95%. Approximately 80% of KS in SSA was estimated attributable to HIV, vs ~50% in the rest of the world. By applying PAFs to national GLOBOCAN estimates, an estimated 19 560 KS cases attributable to HIV were diagnosed in SSA in 2020 (~80% of the worldwide burden), vs 5064 cases of non-HIV-attributable KS (~60% of the worldwide burden). Incidence of HIV-attributable KS was highest in Southern Africa (6.0 cases per 100 000) and Eastern Africa (3.4), which were also the world regions with highest incidence of non-HIV-attributable KS (0.4 and 1.0 cases per 100 000, respectively). This first systematic effort to produce a global picture of KS burden stratified by HIV status highlights the continuing important burden of HIV-attributable KS in SSA, even in the era of combined antiretroviral therapy.

Age-specific burden of cervical cancer associated with HIV: A global analysis with a focus on sub-Saharan Africa.

HIV substantially worsens human papillomavirus (HPV) carcinogenicity and contributes to an important population excess of cervical cancer, particularly in sub-Saharan Africa (SSA). We estimated HIV- and age-stratified cervical cancer burden at a country, regional and global level in 2020. Proportions of cervical cancer (a) diagnosed in women living with HIV (WLHIV), and (b) attributable to HIV, were calculated using age-specific estimates of HIV prevalence (UNAIDS) and relative risk. These proportions were validated against empirical data and applied to age-specific cervical cancer incidence (GLOBOCAN 2020). HIV was most important in SSA, where 24.9% of cervical cancers were diagnosed in WLHIV, and 20.4% were attributable to HIV (vs 1.3% and 1.1%, respectively, in the rest of the world). In all world regions, contribution of HIV to cervical cancer was far higher in younger women (as seen also in empirical series). For example, in Southern Africa, where more than half of cervical cancers were diagnosed in WLHIV, the HIV-attributable fraction decreased from 86% in women ≤34 years to only 12% in women ≥55 years. The absolute burden of HIV-attributable cervical cancer (approximately 28 000 cases globally) also shifted toward younger women: in Southern Africa, 63% of 5341 HIV-attributable cervical cancer occurred in women <45 years old, compared to only 17% of 6901 non-HIV-attributable cervical cancer. Improved quantification of cervical cancer burden by age and HIV status can inform cervical cancer prevention efforts in SSA, including prediction of the impact of WLHIV-targeted vs general population approaches to cervical screening, and impact of HIV prevention.

Estimates of the global burden of cervical cancer associated with HIV.

BACKGROUND: HIV enhances human papillomavirus (HPV)-induced carcinogenesis. However, the contribution of HIV to cervical cancer burden at a population level has not been quantified. We aimed to investigate cervical cancer risk among women living with HIV and to estimate the global cervical cancer burden associated with HIV. METHODS: We did a systematic literature search and meta-analysis of five databases (PubMed, Embase, Global Health [CABI.org], Web of Science, and Global Index Medicus) to identify studies analysing the association between HIV infection and cervical cancer. We estimated the pooled risk of cervical cancer among women living with HIV across four continents (Africa, Asia, Europe, and North America). The risk ratio (RR) was combined with country-specific UNAIDS estimates of HIV prevalence and GLOBOCAN 2018 estimates of cervical cancer to calculate the proportion of women living with HIV among women with cervical cancer and population attributable fractions and age-standardised incidence rates (ASIRs) of HIV-attributable cervical cancer. FINDINGS: 24 studies met our inclusion criteria, which included 236 127 women living with HIV. The pooled risk of cervical cancer was increased in women living with HIV (RR 6·07, 95% CI 4·40-8·37). Globally, 5·8% (95% CI 4·6-7·3) of new cervical cancer cases in 2018 (33 000 new cases, 95% CI 26 000-42 000) were diagnosed in women living with HIV and 4·9% (95% CI 3·6-6·4) were attributable to HIV infection (28 000 new cases, 20 000-36 000). The most affected regions were southern Africa and eastern Africa. In southern Africa, 63·8% (95% CI 58·9-68·1) of women with cervical cancer (9200 new cases, 95% CI 8500-9800) were living with HIV, as were 27·4% (23·7-31·7) of women in eastern Africa (14 000 new cases, 12 000-17 000). ASIRs of HIV-attributable cervical cancer were more than 20 per 100 000 in six countries, all in southern Africa and eastern Africa. INTERPRETATION: Women living with HIV have a significantly increased risk of cervical cancer. HPV vaccination and cervical cancer screening for women living with HIV are especially important for countries in southern Africa and eastern Africa, where a substantial HIV-attributable cervical cancer burden has added to the existing cervical cancer burden. FUNDING: WHO, US Agency for International Development, and US President's Emergency Plan for AIDS Relief.

Evaluating the incidence of inflammatory breast cancer using population- and hospital-based cancer registries in Casablanca, Morocco.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare and aggressive type of breast cancer (BC). Physicians have difficulty diagnosing it correctly given its clinical nature. Previous studies have shown that North Africa compared to the United States has a higher proportion of IBC relative to all BC. PURPOSE: The purpose of this study was to calculate a corrected IBC incidence rate using the population-based registry of Casablanca and other, local hospital-based data sources and to characterize the clinical presentation and basis of diagnosis of IBC. METHODS: We retrieved the Casablanca registry data from 2009-2012, and matched its data with demographic and clinical data from the medical records, logbooks and a local epidemiologic IBC case-control study. A corrected incidence was calculated after accounting for missed cases in the registry. RESULTS: The data showed that the incidence of IBC in the registry was significantly underestimated when the population-based and hospital data were combined. CONCLUSIONS: Population-based registries should focus on specific measures for verifying the diagnosis of IBC since physicians may miss documenting the disease in medical records. This study may have implications for better reporting and documentation of IBC in hospital- and population-based cancer registries in Morocco and other similar countries.