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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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. Methods: We included 116 cervical tissue samples from three groups of Nigerian women in this study: (1) HIV+/ICC+ (n = 39); (2) HIV+/ICC- (n = 53); and (3) HIV-/ICC + (n = 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 t-tests. We additionally performed a receiver operating characteristics (ROC) curve analysis to illustrate the area under the curve (AUC) of EAA in ICC. Results: 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 (P = 0.005). PhenoAA was 20.7 and 7.1 years higher in tumor tissues compared to surrounding normal tissues among HIV-positive women (P = 0.009) and HIV-negative women (P = 0.284), respectively. We did not find substantial differences in PhenoAA between HIV-positive and HIV-negative women with ICC. Conclusion: 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.

Original languageEnglish (US)
Article number834800
JournalFrontiers in Public Health
Volume10
DOIs
StatePublished - Apr 29 2022

Keywords

  • DNA methylation
  • epigenetic age acceleration
  • human immunodeficiency virus
  • invasive cervical cancer
  • LMIC

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health

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