Low T-cell subsets prior to development of virus-associated cancer in HIV-seronegative men who have sex with men

Anupriya Dutta, Hajime Uno, David R. Lorenz, Steven M. Wolinsky, Dana Gabuzda*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Immunological parameters that influence susceptibility to virus-associated cancers in HIV-seronegative individuals are unclear. We conducted a case–control cohort study of immunological parameters associated with development of incident virus-associated cancers among 532 HIV-seronegative men who have sex with men (MSM) enrolled in the Multicenter AIDS Cohort Study (MACS) with median (IQR) 21 (8–26) years of follow-up. Thirty-two incident virus-associated cancers (anal cancer, non-Hodgkin lymphoma, liver cancer, other cancers with etiologies linked to human papillomavirus, Epstein–Barr virus, hepatitis B virus, or human herpesvirus-8) were identified among 3,408 HIV-seronegative men in the MACS during 1984–2010. Cases were matched for demographics, smoking, and follow-up to 500 controls without cancer. Mixed-effects and Cox regression models were used to examine associations between nadir or recent CD4, CD8, and white blood cell (WBC) counts or CD4:CD8 ratios and subsequent diagnosis of virus-associated cancers. Men with incident virus-associated cancers had lower CD4 and WBC counts over a 6-year window prior to diagnosis compared to men without cancer (p = 0.001 and 0.03, respectively). Low CD4 cell count and nadir, CD4 count-nadir differential, and CD4:CD8 ratio nadir were associated with increased 2-year risk of incident virus-associated cancers in models adjusted for demographics and smoking (hazard ratios 1.2–1.3 per 100 or 0.1 unit decrease, respectively; p < 0.01). Other associated factors included heavy smoking and past or current hepatitis B virus infection. These findings show that low CD4 cell counts, CD4 nadir, and CD4:CD8 cell ratios are independent predictors for subsequent risk of virus-associated cancers in HIV-seronegative MSM.

Original languageEnglish (US)
Pages (from-to)1131-1142
Number of pages12
JournalCancer Causes and Control
Issue number11
StatePublished - Nov 1 2018


  • CD4 T cells
  • CD8 T cells
  • Cancer risk
  • HBV
  • Lymphopenia
  • Oncogenic viruses

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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