The distribution of hrHPV genotypes among cervical cancer cases diagnosed across Ghana: a cross-sectional study.

BACKGROUND: The burden of cervical cancer in Ghana is high due to a lack of a national screening and vaccination program. Geographical variations in high-risk Human Papilloma Virus incidence and type should be considered for vaccine improvement and screening in LMICs. METHODS: A descriptive, multi-center cross-sectional study with purposive sampling of cases with cervical cancer diagnosed from January 2012 through to December 2018 was employed relying on archived Formalin Fixed Paraffin Embedded (FFPE) tissues from four (4) Teaching Hospitals. Cervical cancers were assessed for histopathological features following WHO guidelines. In addition, the novel Tumour Budding and Nest Size Grade (TBNS) for SCC, SILVA pattern of invasion for EAC and Tumour Infiltrating Lymphocytes (TILs) were assessed. High Risk HPV testing was performed using an isothermal, multiplex nucleic acid amplification method from ATILA biosystem (Mountain View California, USA). The FFPE blocks were tested for 15 hrHPV genotypes. Results were analyzed using SPSS v.26.0, with descriptive statistics and cross-tabulation and chi-square tests done with significance established at p < 0.05. RESULTS: A total of 297 cases were identified for the study with ages ranging from 20 to 95 years. The peak age group for cervical cancer was 46 to 55 years. For those tested, hrHPV positivity rate was 85.4% [EAC (84.6%) and SCC (85.6%)]. The top five hrHPV serotypes for both histological cancers were 59 (40.0%), 35 (32.0%), 18 (30.0%), 16 (15.0%), and 33 (10.0%) respectively. Approximately, 58.2% of infections were multiple. Single hrHPV infections were mostly caused by hrHPV 59 (28.9%), and 16 (26.3%). TBNS grade for SCC, SILVA pattern of invasion for EAC and TILs did not show any statistically significant relationship with hrHPV. CONCLUSION: We affirm reported differences in hrHPV types associated with cervical cancer in Ghana with hrHPV types such as 59, 35, and 33 forming a significant proportion of hrHPV types associated with cervical cancer. This difference in hrHPV types should guide vaccine improvement and triaging of hrHPV positives. Though multiple infections are more common, some hrHPV types such as hrHPV 16 and 59 are responsible for most single infections associated with cervical cancer. Simple haematoxylin and eosin-based morphological assessments can improve the prognostication of patients with cervical cancer.

Heterogeneous genetic architectures and evolutionary genomics of prostate cancer in Sub-Saharan Africa.

Men of African descent have the highest prostate cancer (CaP) incidence and mortality rates, yet the genetic basis of CaP in African men has been understudied. We used genomic data from 3,963 CaP cases and 3,509 controls recruited in Ghana, Nigeria, Senegal, South Africa, and Uganda, to infer ancestry-specific genetic architectures and fine-mapped disease associations. Fifteen independent associations at 8q24.21, 6q22.1, and 11q13.3 reached genome-wide significance, including four novel associations. Intriguingly, multiple lead SNPs are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of CaP differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African CaP associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations.

Validation of a multi-ancestry polygenic risk score and age-specific risks of prostate cancer: A meta-analysis within diverse populations.

Background: We recently developed a multi-ancestry polygenic risk score (PRS) that effectively stratifies prostate cancer risk across populations. In this study, we validated the performance of the PRS in the multi-ancestry Million Veteran Program and additional independent studies. Methods: Within each ancestry population, the association of PRS with prostate cancer risk was evaluated separately in each case-control study and then combined in a fixed-effects inverse-variance-weighted meta-analysis. We further assessed the effect modification by age and estimated the age-specific absolute risk of prostate cancer for each ancestry population. Results: The PRS was evaluated in 31,925 cases and 490,507 controls, including men from European (22,049 cases, 414,249 controls), African (8794 cases, 55,657 controls), and Hispanic (1082 cases, 20,601 controls) populations. Comparing men in the top decile (90-100% of the PRS) to the average 40-60% PRS category, the prostate cancer odds ratio (OR) was 3.8-fold in European ancestry men (95% CI = 3.62-3.96), 2.8-fold in African ancestry men (95% CI = 2.59-3.03), and 3.2-fold in Hispanic men (95% CI = 2.64-3.92). The PRS did not discriminate risk of aggressive versus nonaggressive prostate cancer. However, the OR diminished with advancing age (European ancestry men in the top decile: ≤55 years, OR = 7.11; 55-60 years, OR = 4.26; >70 years, OR = 2.79). Men in the top PRS decile reached 5% absolute prostate cancer risk ~10 years younger than men in the 40-60% PRS category. Conclusions: Our findings validate the multi-ancestry PRS as an effective prostate cancer risk stratification tool across populations. A clinical study of PRS is warranted to determine whether the PRS could be used for risk-stratified screening and early detection. Funding: This work was supported by the National Cancer Institute at the National Institutes of Health (grant numbers U19 CA214253 to C.A.H., U01 CA257328 to C.A.H., U19 CA148537 to C.A.H., R01 CA165862 to C.A.H., K99 CA246063 to B.F.D, and T32CA229110 to F.C), the Prostate Cancer Foundation (grants 21YOUN11 to B.F.D. and 20CHAS03 to C.A.H.), the Achievement Rewards for College Scientists Foundation Los Angeles Founder Chapter to B.F.D, and the Million Veteran Program-MVP017. This research has been conducted using the UK Biobank Resource under application number 42195. This research is based on data from the Million Veteran Program, Office of Research and Development, and the Veterans Health Administration. This publication does not represent the views of the Department of Veteran Affairs or the United States Government.