AUTHOR=Musa Jonah , Kim Kyeezu , Zheng Yinan , Qu Yishu , Joyce Brian T. , Wang Jun , Nannini Drew R. , Gursel Demirkan B. , Silas Olugbenga , Abdulkareem Fatimah B. , Imade Godwin , Akanmu Alani S. , Wei Jian-Jun , Kocherginsky Masha , Kim Kwang-Youn A. , Wehbe Firas , Achenbach Chad J. , Anorlu Rose , Simon Melissa A. , Sagay Atiene , Ogunsola Folasade T. , Murphy Robert L. , Hou Lifang 

TITLE=Accelerated Epigenetic Age Among Women with Invasive Cervical Cancer and HIV-Infection in Nigeria

JOURNAL=Frontiers in Public Health

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2022.834800

DOI=10.3389/fpubh.2022.834800

ISSN=2296-2565

ABSTRACT=<sec><title>Background</title><p>Invasive cervical cancer (ICC) is a serious public health burden in Nigeria, where human immunodeficiency virus (HIV) remains highly prevalent. Previous research suggested that epigenetic age acceleration (EAA) could play a role in detection of HIV-associated ICC. However, little research has been conducted on this topic in Africa where the population is most severely affected by HIV-associated ICC. Here, we investigated the association between ICC and EAA using cervical tissues of ICC-diagnosed Nigerian women living with HIV.</p></sec><sec><title>Methods</title><p>We included 116 cervical tissue samples from three groups of Nigerian women in this study: (1) HIV+/ICC+ (<italic>n</italic> = 39); (2) HIV+/ICC- (<italic>n</italic> = 53); and (3) HIV-/ICC + (<italic>n</italic> = 24). We utilized four DNA methylation-based EAA estimators; IEAA, EEAA, GrimAA, and PhenoAA. We compared EAA measurements across the 3 HIV/ICC groups using multiple linear regression models. We also compared EAA between 26 tumor tissues and their surrounding normal tissues using paired <italic>t</italic>-tests. We additionally performed a receiver operating characteristics (ROC) curve analysis to illustrate the area under the curve (AUC) of EAA in ICC.</p></sec><sec><title>Results</title><p>We found the most striking associations between HIV/ICC status and PhenoAge acceleration (PhenoAA). Among HIV-positive women, PhenoAA was on average 13.4 years higher in women with ICC compared to cancer-free women (<italic>P</italic> = 0.005). PhenoAA was 20.7 and 7.1 years higher in tumor tissues compared to surrounding normal tissues among HIV-positive women (<italic>P</italic> = 0.009) and HIV-negative women (<italic>P</italic> = 0.284), respectively. We did not find substantial differences in PhenoAA between HIV-positive and HIV-negative women with ICC.</p></sec><sec><title>Conclusion</title><p>PhenoAA is associated with ICC in HIV-infected women in our study. Our findings suggest that PhenoAA may serve as a potential biomarker for further risk stratification of HIV-associated ICC in Nigeria and similar resource-constrained settings.</p></sec>