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An estimated 38 million people live with human immunodeficiency virus (HIV) worldwide and are at excess risk for multiple cancer types. Elevated cancer risks in people living with HIV (PLWH) are driven primarily by increased exposure to carcinogens, most notably oncogenic viruses acquired through shared transmission routes, plus acceleration of viral carcinogenesis by HIV-related immunosuppression. In the era of widespread antiretroviral therapy (ART), life expectancy of PLWH has increased, with cancer now a leading cause of co-morbidity and death. Furthermore, the types of cancers occurring among PLWH are shifting over time and vary in their relative burden in different parts of the world. In this context, the International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) convened a meeting in September 2022 of multinational and multidisciplinary experts to focus on cancer in PLWH. This report summarizes the proceedings, including a review of the state of the science of cancer descriptive epidemiology, etiology, molecular tumor characterization, primary and secondary prevention, treatment disparities and survival in PLWH around the world. A consensus of key research priorities and recommendations in these domains is also presented.

INTRODUCTION: Gastric cancer (GC) is the third leading cause of global cancer-related mortality. Despite the shifting burden of GC to low-and middle-income countries, the data regarding incidence, treatment, and outcomes in these settings are sparse. The primary aim of this systematic review was to aggregate all available data on GC in sub-Saharan Africa (SSA) to describe the variability in incidence across the region. METHODS: Studies reporting population-based primary data on GC in SSA were considered. The inclusion was limited to primary studies published between January 1995 and March 2022 which comprised of adult patients in SSA with GC. Studies without accessible full text in either French or English language were excluded. Unadjusted GC incidence rates with their standard errors for each study were recalculated from the crude numerators and denominators provided in individual studies. RESULTS: A total of 5,626 articles were identified in the initial search, of which, 69 studies were retained. Reported incidence rates ranged from a high of 5.56 GC cases per 100,000 in Greater Meru Kenya to a low of 0.04 GC cases per 100,000 people in Benin City Nigeria. The overall crude pooled incidence was 1.20 GC cases per 100, 000 (95%CI 1.15-1.26) with a variability of 99.83% (I2 p < 0.001). From the 29 high-quality population-based registry studies the crude pooled incidence was 1.71 GC cases per 100,000 people (95%CI 1.56-21.88) with a variability of 99.60%. CONCLUSION: This systemic review demonstrates that GC incidence is highly variable across SSA. The limited data on GC treatment, mortality, and survival presents a significant challenge to providing a complete epidemiologic description of the burden of GC in SSA. There is a need for further robust data collection, exploration, and research studies on cancer care in SSA, with continued assessment of primary data availability.

Abstract Background Disparities in invasive cervical cancer (ICC) incidence exist globally, particularly in HIV positive women who are at elevated risk compared to HIV negative women. We aimed to determine the spatial, temporal, and spatiotemporal incidence of ICC and the potential risk factors among HIV positive women in South Africa. Methods We included ICC cases in women diagnosed with HIV from the South African HIV cancer match study during 2004–2014. We used the Thembisa model, a mathematical model of the South African HIV epidemic to estimate women diagnosed with HIV per municipality, age group and calendar year. We fitted Bayesian hierarchical models, using a reparameterization of the Besag-York-Mollié to capture spatial autocorrelation, to estimate the spatiotemporal distribution of ICC incidence among women diagnosed with HIV. We also examined the association of deprivation, access to health (using the number of health facilities per municipality) and urbanicity with ICC incidence. We corrected our estimates to account for ICC case underascertainment, missing data and data errors. Results We included 17,821 ICC cases and demonstrated a decreasing trend in ICC incidence, from 306 to 312 in 2004 and from 160 to 191 in 2014 per 100,000 person-years across all municipalities and corrections. The spatial relative rate (RR) ranged from 0.27 to 4.43 in the model without any covariates. In the model adjusting for covariates, the most affluent municipalities had a RR of 3.18 (95% Credible Interval 1.82, 5.57) compared to the least affluent ones, and municipalities with better access to health care had a RR of 1.52 (1.03, 2.27) compared to municipalities with worse access to health. Conclusions The results show an increased incidence of cervical cancer in affluent municipalities and in those with more health facilities. This is likely driven by better access to health care in more affluent areas. More efforts should be made to ensure equitable access to health services, including mitigating physical barriers, such as transportation to health centres and strengthening of screening programmes.

Human papillomavirus (HPV) proteins may elicit antibody responses in the process toward HPV‐related malignancy. However, HPV seroepidemiology in noncervical HPV‐related cancers remains poorly understood, particularly in populations with a high prevalence of human immunodeficiency virus (HIV). Using a glutathione S‐transferase‐based multiplex serology assay, antibodies against E6, E7 and L1 proteins of HPV16 and HPV18 were measured in sera of 535 cases of noncervical HPV‐related cancers (anal (n = 104), vulval (n = 211), vaginal (n = 49), penile (n = 37) and oropharyngeal (n = 134)) and 6651 non‐infection‐related cancer controls, from the Johannesburg Cancer Study that recruited Black South African with newly diagnosed cancer between 1995 and 2016. Logistic and Poisson regression models were used to calculate adjusted odds ratios (aOR) and prevalence ratios (aPR) and 95% confidence intervals (CI) in cases versus controls. HPV16 E6 was more strongly associated with noncervical HPV‐related cancers than HPV16 L1 or E7, or HPV18 proteins: anal (females (HPV16 E6 aOR = 11.50;95%CI:6.0–22.2), males (aOR = 10.12;95%CI:4.9–20.8), vulval (aOR = 11.69;95%CI:7.9–17.2), vaginal (aOR = 10.26;95%CI:5.0–21), penile (aOR = 18.95;95%CI:8.9–40), and oropharyngeal (females (aOR = 8.95;95%CI:2.9–27.5), males (aOR = 3.49;95%CI:1.8–7.0)) cancers. HPV16‐E6 seropositivity ranged from 24.0% to 35.1% in anal, vulval, vaginal and penile cancer but was significantly lower (11.2%) in oropharyngeal cancer. After adjustment for HIV, prevalence of which increased from 22.2% in 1995–2005 to 54.1% in 2010–2016, HPV16 E6 seropositivity increased by period of diagnosis (aPR for 2010–2016 vs. 1995–2006 = 1.84;95%CI:1.1–3.0). Assuming HPV16 E6 seroprevalence reflects HPV attributable fraction, the proportion of certain noncervical‐HPV‐related cancers caused by HPV is increasing over time in South Africa. This is expected to be driven by the increasing influence of HIV. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is the leading cause of cancer-related morbidity and mortality in women living in South Africa, a country with a high HIV burden. However, characteristics of the double burden of HIV and BC in South Africa have not been properly investigated. We described characteristics of BC cases by HIV status in South Africa. Methods: In this nationwide South African study, we obtained BC records for women aged ≥15 years diagnosed in the public health sector between January 2004 and December 2014. We included records from the National Cancer Registry that had been linked to HIV-related laboratory records from the National Health Laboratory Service. We assessed the odds of being HIV positive versus HIV negative in relation to patient-, cancer-, and municipality-related characteristics. Results: From 2004–2014, 40 520 BC cases were diagnosed in women aged ≥15 years. Of these, 73.5% had unknown HIV status, 18.7% were HIV negative, and 7.7% were HIV positive. The median age at BC diagnosis was 43 years (interquartile range [IQR]: 37–52) in HIV positive and 57 years (IQR: 46–68) in HIV negative women, respectively. The odds of being HIV positive was higher for women who were aged 30–34 years compared to women aged 35–39 years at cancer diagnosis (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.10–1.71), Black versus non-Black (OR 6.41, 95% CI 5.68–7.23), diagnosed with cancer in rural versus urban areas (OR 1.59, 95% CI 1.40–1.82) and diagnosed in municipalities with low and middle (OR 3.46, 95% CI 2.48–4.82) versus high socioeconomic position (OR 2.69, 95% CI 2.11–3.42). Conclusion: HIV status was unknown for the majority of BC patients. Among those with known HIV status, being HIV positive was associated with a younger age at cancer diagnosis, being Black and receiving care in municipalities of poor socioeconomic position. Future studies should examine opportunities to integrate HIV and BC control programs. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to map place of cancer diagnosis in relation to Human Immunodeficiency Virus (HIV) care centre among people living with HIV (PLHIV) within South Africa (SA) using national laboratory database. Design: We linked HIV and cancer laboratory data from 2004–2014 using supervised machine-learning algorithms. We performed a cross-sectional analysis comparing province where individuals accessed their HIV care versus where they had their cancer diagnosis. Setting: We used laboratory test records related to HIV diagnostics and care, such as CD4 cell counts and percentages, rapid tests, qualitative Polymerase Chain Reaction (PCR), antibody and antigen tests for HIV data that was documented as HIV positive and laboratory diagnosed cancer records from SA. Study population: Our study population consisted of HIV records from the National Health Laboratory Service (NHLS) that linked to cancer record at the National Cancer Registry (NCR) between 2004–2014. Primary and secondary outcomes: We linked HIV records from NHLS to cancer records at NCR in order to study the inherent characteristics of the population with both HIV and cancer. Results: The study population was 68,284 individuals with cancer and documented HIV related laboratory test. The median age at cancer diagnosis was 40 [IQR, 33–48] years for the study population with most cancers in PLHIV diagnosed in females 70.9% [n = 46,313]. Of all the PLHIV and cancer, 25% (n = 16,364 p < 0.001) sought treatment outside their province of residence with 60.7% (n = 10,235) travelling to Gauteng. KZN had 46.6% (n = 4,107) of its PLHIV getting cancer diagnosis in Gauteng. Western Cape had 95% (n = 6,200) of PLHIV getting cancer diagnosis within the province. Conclusions: Our results showed health systems inequalities across provinces in SA with respect to cancer diagnosis. KZN for example had nearly half of the PLHIV getting cancer diagnosis outside the province while Western Cape is able to offer cancer diagnostic services to most of the PLHIV in the province. Gauteng is getting over burdened with referral for cancer diagnosis from other provinces. More effort is required to ensure equitable access to cancer diagnostic services within the country. [ABSTRACT FROM AUTHOR]

Aims To describe the incidence and epidemiology of conjunctival squamous cell carcinoma (CSCC) in South Africa over a 25-year period (1994-2018), with particular reference to the HIV epidemic. Methods Incident cases of histologically diagnosed CSCC were identified from the pathology-based South African National Cancer Registry. Crude and direct age-standardised incidence rates (ASIRs) per 100 000 persons (Segi World Standard Population) were calculated using national population statistics and compared by age, sex and ethnicity. Trends in the incidence and demographic features of CSCC were described and analysed. Incidence rates were compared with national HIV-related statistics for the same time period. Results In total, there were 9016 reported CSCC cases (women: 56.6%, black: 86.8%, mean age: 41.5 years). The overall ASIR was 0.78 per 100 000. Two distinct epidemiological patterns were identified: (1) older white men, and (2) younger black women. There was a sixfold increase in CSCC incidence rates between 1994 and 2009 with a corresponding shift from the first to the second disease profile. Despite rising HIV seroprevalence, CSCC incidence rates have declined since 2009. A strong ecological correlation (r=0.96) between CSCC incidence and widespread antiretroviral therapy (ART) provision was identified. Conclusion This study highlights the evolving trends and disease burden of CSCC in South Africa. Widespread ART provision is ecologically correlated with declining CSCC rates over the last decade. These findings are in keeping with reported trends for other HIV-related cancers and have important implications for future incidence studies and public health policy. [ABSTRACT FROM AUTHOR]

Breast and gynaecologic cancers account for approximately half of all cancers diagnosed amongst women in South Africa, many of whom also live with HIV. We aimed to determine the incidence of and risk factors for developing breast and gynaecologic cancers in women living with HIV (WLHIV) in South Africa. This is a longitudinal analysis of the South African HIV Cancer Match study including women aged ≥15 years with two or more HIV‐related laboratory tests. We used Cox proportional hazard models to determine the association of Human Papilloma Virus (HPV)‐related and hormone‐related gynaecologic cancer with patient‐ and municipal‐level characteristics. From 3 447 908 women and 10.5 million years of follow‐up, we identified 11 384 incident and 7612 prevalent gynaecologic and breast cancers. The overall crude incidence rate was 108/1 00 000 person‐years (pyears) (95% confidence interval [CI]: 106‐110), with the highest incidence observed for cervical cancer (70/1 00 000 pyears; 95% CI: 68.5‐71.7). Low CD4 cell counts and high HIV RNA viral loads increased the risk of cervical and other HPV‐related cancers. Age was associated with both HPV‐related and hormone‐related cancers. Women accessing health facilities in high socioeconomic position (SEP) municipalities were more likely to be diagnosed with HPV‐related cancers and breast cancer than women accessing care in low SEP municipalities. It is important to improve the immunologic status of WLHIV as part of cancer prevention strategies in WLHIV. Cancer prevention and early detection programmes should be tailored to the needs of women ageing with HIV. In addition, SEP disparities in cancer diagnostic services have to be addressed. [ABSTRACT FROM AUTHOR]

Background Old age is an important risk factor for developing cancer, but few data exist on this association in people with human immunodeficiency virus (HIV, PWH) in sub-Saharan Africa. Methods The South African HIV Cancer Match study is a nationwide cohort of PWH based on a linkage between HIV-related laboratory records from the National Health Laboratory Service and cancer diagnoses from the National Cancer Registry for 2004–2014. We included PWH who had HIV-related tests on separate days. Using natural splines, we modeled cancer incidence rates as a function of age. Results We included 5 222 827 PWH with 29 580 incident cancer diagnoses—most commonly cervical cancer (n = 7418), Kaposi sarcoma (n = 6380), and breast cancer (n = 2748). In young PWH, the incidence rates for infection-related cancers were substantially higher than for infection-unrelated cancers. At age 40 years, the most frequent cancer was cervical cancer in female and Kaposi sarcoma in male PWH. Thereafter, the rates of infection-unrelated cancers increased steeply, particularly among male PWH, where prostate cancer became the most frequent cancer type at older age. Whereas Kaposi sarcoma rates peaked at 34 years (101/100 000 person-years) in male PWH, cervical cancer remained the most frequent cancer among older female PWH. Conclusions Infection-related cancers are common in PWH in South Africa, but rates of infection-unrelated cancers overtook those of infection-related cancers after age 54 years in the overall study population. As PWH in South Africa live longer, prevention and early detection of infection-unrelated cancers becomes increasingly important. Meanwhile, control strategies for infection-related cancers, especially cervical cancer, remain essential. [ABSTRACT FROM AUTHOR]

South Africa's HIV epidemic has evolved over time in terms of numbers of people living with HIV, access to antiretroviral treatment (ART) and age. These changes have profoundly influenced local cancer patterns. The Johannesburg Cancer Study has, over a period of 22 years (1995‐2016), recruited over 20 000 incident black cancer patients who consented to provide answers to a questionnaire and blood samples (serum, DNA). This has presented a unique opportunity to examine the evolving association of HIV with cancer in Africa. We used logistic regression models to explore case‐control associations between specific cancers and HIV, using participants with non‐infection related cancers as controls. Using data of 20 835 cancer patients with confirmed HIV status, we found the following cancers to be associated with HIV: Kaposi's sarcoma (ORadj; 95%CI): (99.1;72.6‐135.1), non‐Hodgkin lymphoma (11.3;9.3‐13.6), cervical cancer (2.7;2.4‐3.0), Hodgkin lymphoma (3.1;2.4‐4.2), cancer of the eye/conjunctiva (18.7;10.1‐34.7), anogenital cancers (anus [2.1;1.4‐3.2], penis [5.4;2.7‐10.5], vulva [4.8;3.5‐6.4], vagina [5.5;3.0‐10.2]), oropharyngeal cancer (1.6;1.3‐1.9), squamous cell carcinoma of the skin (3.5;2.4‐4.9), melanoma (2.0;1.2‐3.5) and cancer of the larynx (1.7;1.3‐2.4). Kaposi's sarcoma odds ratios increased from the pre‐ART (1995‐2004) to the early ART (2005‐2009) period but declined in the late ART (2010‐2016) period. Odds ratios for cancers of the eye/conjunctiva, cervix, penis and vulva continued to increase in recent ART periods. Our study confirms the spectrum of HIV‐associated cancers found in other African settings. The odds ratios of conjunctival and HPV‐related cancers continue to rise in the ART era as the HIV positive population ages. [ABSTRACT FROM AUTHOR]

We reviewed the literature on the importance of selected anti‐high‐risk human papillomavirus (HR‐HPV) antibodies (namely, 16/18 and early oncoproteins E6 and E7) as potential serological markers for early detection of individuals at high risk of cervical cancer. We searched for studies in PubMed and Embase databases published from 2010 to 2020 on antibodies against HR‐HPV E6 and E7 early proteins and cervical cancer. Pooled sensitivity and specificity for HPV16 and HPV18 antibodies were calculated using a bivariate hierarchical random‐effects model. A total of 69 articles were identified; we included three studies with 1550 participants. For the three HPV16/18 E6 and E7 antibody tests, enzyme‐linked immunosorbent assay‐based assays had a sensitivity of 18% for detecting CIN2+ (95% confidence interval [CI]: 15–21) and a specificity of 96% (95% CI: 92–98), for slot‐blot, sensitivity was 28.9% (95% CI: 23.3–35.1) and specificity was 72% (95% CI: 66.6–77.0) for detecting CIN2+, and for multiplex HPV serology assay based on a glutathione S‐transferase, sensitivity was 16% (95% CI: 8.45–28.6) and specificity was 98% (95% CI: 97–99) for detecting invasive cervical cancer. HR‐HPV16/18 E6 and E7 serological markers showed high specificity, but sensitivity was suboptimal for the detection of cervical cancer in either population screening settings or as point‐of‐care screening tests. [ABSTRACT FROM AUTHOR]