Mazvita Muchengeti

Antibodies against high‐risk human papillomavirus proteins as markers for noncervical HPV‐related cancers in a Black South African population, according to HIV status

AbstractHuman 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.

Cervical cancer survival in sub‐Saharan Africa by age, stage at diagnosis and Human Development Index: A population‐based registry study

AbstractCervical cancer is the leading cause of cancer death in African women. We sought to estimate population‐based survival and evaluate excess hazards for mortality in African women with cervical cancer, examining the effects of country‐level Human Development Index (HDI), age and stage at diagnosis. We selected a random sample of 2760 incident cervical cancer cases, diagnosed in 2005 to 2015 from 13 population‐based cancer registries in 11 countries (Benin, Cote d'Ivoire, Ethiopia, Kenya, Mauritius, Mozambique, Namibia, Seychelles, South Africa, Uganda and Zimbabwe) through the African Cancer Registry Network. Of these, 2735 were included for survival analyses. The 1‐, 3‐ and 5‐year observed and relative survival were estimated by registry, stage and country‐level HDI. We used flexible Poisson regression models to estimate the excess hazards for death adjusting for age, stage and HDI. Among patients with known stage, 65.8% were diagnosed with Stage III‐IV disease. The 5‐year relative survival for Stage I‐II cervical cancer in high HDI registry areas was 67.5% (42.1‐83.6) while it was much lower (42.2% [30.6‐53.2]) for low HDI registry areas. Independent predictors of mortality were Stage III‐IV disease, medium to low country‐level HDI and age >65 years at cervical cancer diagnosis. The average relative survival from cervix cancer in the 11 countries was 69.8%, 44.5% and 33.1% at 1, 3 and 5 years, respectively. Factors contributing to the HDI (such as education and a country's financial resources) are critical for cervical cancer control in SSA and there is need to strengthen health systems with timely and appropriate prevention and treatment programmes.

Race‐specific temporal trends of HPV ‐related cancers in South Africa: An analysis of the South African National Cancer Registry, 2011–2022

Abstract Evaluating trends in HPV‐related cancer rates by race is essential for identifying high‐risk populations and improving prevention efforts. Using 2011–2022 South African National Cancer Registry data, we analyzed age‐standardized incidence rates by race and sex across three periods (2011–2014, 2015–2018, 2019–2022) using linear regression. Significant increases were observed for oropharyngeal squamous cell carcinoma (SCC) among White females ( p  < .01), vulvar SCC among Asian ( p  < .01) and Black ( p  = .02) females, and anal SCC among Colored females and Black males ( p  < .01). Cervical carcinoma rates remained stable for most racial groups, except for the annual trends showing a 1.9% increase per year (95% CI = 1.0, 2.7) among White females. These findings suggest rising incidence rates for some HPV‐related cancers across racial groups in South Africa. Further research is needed to explore the constellation of risk factors contributing to these trends and to guide targeted interventions.

Cancer in HIV-positive and HIV-negative adolescents and young adults in South Africa: a cross-sectional study

Objective To determine the spectrum of cancers in adolescents and young adults (AYAs) living with and without HIV in South Africa. Design Cross-sectional study with cancer records provided by the National Cancer Registry (NCR) and HIV records from the National Health Laboratory Service (NHLS). Setting and participants The NHLS is the largest provider of pathology services in the South African public sector. The NCR is a division of the NHLS. We included AYAs (aged 10–24 years) diagnosed with cancer by public health sector laboratories between 2004 and 2014 (n=8479). HIV status was obtained through record linkages and text mining. Primary and secondary outcomes We determined the spectrum of cancers by HIV status in AYAs. We used multivariable logistic regression to describe the association of cancer in AYAs with HIV, adjusting for age, sex, ethnicity and calendar period. We imputed (post hoc) the HIV status for AYA with unknown HIV status. Results 8479 AYAs were diagnosed with cancer, HIV status was known for 45% (n=3812). Of those whose status was known, about half were HIV positive (n=1853). AYAs living with HIV were more likely to have Kaposi’s sarcoma (adjusted OR (aOR) 218, 95% CI 89.9 to 530), cervical cancer (aOR 2.18, 95% CI 1.23 to 3.89), non-Hodgkin’s lymphoma (aOR 2.12, 95% CI 1.69 to 2.66) and anogenital cancers other than cervix (aOR 2.73, 95% CI 1.27 to 5.86) than AYAs without HIV. About 44% (n=1062) of AYAs with HIV-related cancers had not been tested for HIV. Conclusions Targeted HIV testing for AYAs diagnosed with cancer, followed by immediate start of antiretroviral therapy, screening for cervical precancer and vaccination against human papilloma virus is needed to decrease cancer burden in AYAs living with HIV in South Africa.

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

AbstractHIV 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.

Thirteen cancers associated with HIV infection in a Black South African cancer patient population (1995‐2016)

AbstractSouth 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.

Usefulness of high‐risk HPV early oncoprotein (E6 and E7) serological markers in the detection of cervical cancer: A systematic review and meta‐analysis

Abstract 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.

Gynaecologic and breast cancers in women living with HIV in South Africa: A record linkage study

AbstractBreast 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.