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

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 [HPV], Epstein-Barr virus [EBV], hepatitis B virus [HBV], or human herpesvirus-8 [HHV-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 six 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 two-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